Big medical encyclopedia and comorbidity. Comorbid disorders. Comorbid lesions of the endocrine system

“We should not treat the disease itself, for which we cannot find a part or name, we should not treat the cause of the disease, which is often unknown to us, the patient, or those around him, but we should treat the patient himself, his composition, his organ, his strength "

Professor M. Ya. Mudrov (actual speech “A word on the way to teach and learn practical medicine”

or active medical art at the bedside of the sick", 1820)

Dear colleagues, in addition to therapists and general practitioners, narrow specialists often encounter the problem of comorbidity. Unfortunately, they extremely rarely pay attention to the coexistence of a whole spectrum of diseases in one patient and primarily treat a specialized disease. In current practice, urologists, gynecologists, otorhinolaryngologists, ophthalmologists, surgeons and other medical specialists often include only “their” disease in the diagnosis, leaving the search for concomitant pathology to other specialists. The unspoken rule of any specialized department has become the advisory work of the therapist, who takes upon himself the syndromic analysis of the patient, as well as the formation of a diagnostic and treatment concept that takes into account the patient’s potential risks and his long-term prognosis.

Everything in the body is connected (thank God, few people deny this fact). Not a single function, not a single organ, not a single system works in isolation. Their continuous joint activity maintains homeostasis, ensures the coherence of ongoing processes, and protects the body. However, in real life, this mechanism, ideal from the point of view of nature, encounters every second a multitude of pathological agents, under the influence of which its individual components fail, leading to the development of the disease. If it happens, hundreds of adaptive and protective mechanisms will launch thousands of chemical reactions and physiological processes aimed at suppressing, limiting and completely eliminating the disease, as well as preventing its complications.

Nothing passes without a trace. The disruption of one seemingly tiny link, despite the timely elimination of the defect, entails changes in many processes, mechanisms and functions. This contributes to the emergence of new diseases, the debut of which may take many years. In addition, such a violent response of the body to the influence of a pathological agent is not always possible. Its protective powers are lost with age, and also fade away against the background of immunodeficiency, due to a wide range of reasons.

There are no specific diseases. However, doctors often prevent, diagnose and treat a patient’s disease in isolation, paying insufficient attention to the illnesses the person has suffered and its concomitant pathology. The practical process drags on as usual from year to year, as if the patient had only one illness, as if only it needed to be treated. Medicine is forced to become commonplace. From the point of view of modern medicine, this state of affairs cannot continue to persist, and therefore it would be more correct to consider the current disease and look for approaches to it in conjunction with an analysis of past diseases, risk factors and predictors available to the patient, as well as with calculation of the likelihood of potentially possible complications.

An individual approach to the patient dictates the need for a comprehensive study of the clinical picture of the underlying, concomitant and past diseases, as well as their comprehensive diagnosis and rational treatment. This is precisely the essence of the famous principle of Russian doctors, voiced in the epigraph to our article, which has become the property of world medicine and the subject of many years of discussion among domestic and foreign scientists and clinicians. However, long before Mudrov, Zakharyin, Pirogov and Botkin, who proclaimed this principle of managing somatic patients in Russia, traditional medicine arose in Ancient China, using an integrated approach to the treatment of the human body, a complete diagnosis of diseases, coupled with the general improvement of the body and its unity with nature. In Ancient Greece, the great thinker and physician Hippocrates wrote: “Examination of the body is a whole business: it requires knowledge, hearing, smell, touch, language, reasoning.” He, contrary to his opponents, was convinced of the need to search for the deeply hidden cause of the disease, and not to eliminate only its symptoms. The healers of Ancient Egypt, Babylonia and Central Asia were also aware of the relationship between some diseases and others. More than four thousand years ago, they knew how to diagnose diseases using the pulse, the measurement of which today is used only in the diagnosis of heart disease. Many centuries ago, generations of doctors promoted the advisability of an integrated approach in identifying the disease and healing the patient, but modern medicine, characterized by an abundance of diagnostic techniques and a variety of treatment procedures, required specification. In this regard, the question has arisen: how to comprehensively assess a patient suffering from several diseases at the same time, where to begin his examination and where to focus treatment in the first and subsequent stages?

For many years this question remained open, until in 1970 Alvan Feinstein, an outstanding American physician, researcher and epidemiologist who had a significant influence on the technique of clinical research, and especially in the field of clinical epidemiology, proposed the concept of “comorbidity” (lat. co - together, morbus - disease). He put into this term the idea of the presence of an additional clinical picture that already exists or may appear independently, in addition to the current disease, and is always different from it. Professor A. Feinstein demonstrated the phenomenon of comorbidity using the example of somatic patients with acute rheumatic fever, finding a worse prognosis for patients suffering from several diseases simultaneously.

Immediately shortly after the discovery of comorbidity, it was identified as a separate research area. A broad study of the combination of somatic and mental pathology has found a place in psychiatry. I. Jensen (1975), J. H. Boyd and J. D. Burke (1984), W. C. Sanderson (1990), U. L. Nuller (1993), L. Robins (1994), A. B. Smulevich (1997), C. R. Cloninger (2002) and other leading psychiatrists have devoted many years to identifying a number of comorbid conditions in patients with a variety of mental disorders. It was these researchers who developed the first models of comorbidity. Some of the open models viewed comorbidity as the presence of more than one disorder in a person at a given time in life, while others viewed it as the relative risk of a person with one disorder acquiring another disorder. These scientists identified transsyndromal, transnosological and chronological comorbidity. The former represent the coexistence in one patient of two and/or more syndromes or diseases that are pathogenetically interrelated, and the latter type requires their temporary coincidence. This classification was largely inaccurate, but it made it possible to understand that comorbidity can be associated with a single cause or common mechanisms of pathogenesis of these conditions, which is sometimes explained by the similarity of their clinical manifestations, which does not allow accurately differentiating nosologies.

The problem of the influence of comorbidity on the clinical course of the underlying somatic disease, the effectiveness of drug therapy, and the immediate and long-term prognosis of patients has been studied by talented clinicians and scientists from various medical specialties in many countries around the world. Among them were M. H. Kaplan (1974), M. E. Charlson (1987), F. G. Schellevis (1993), H. C. Kraemer (1995), M. van den Akker (1996), T. Pincus ( 1996), A. Grimby (1997), S. Greenfield (1999), M. Fortin (2004), A. Vanasse (2005) and C. Hudon (2005), L. B. Lazebnik (2005), A. L. Vertkin and O. V. Zairatyants (2008), G. E. Caughey (2008), F. I. Belyalov (2009), L. A. Luchikhin (2010) and many others. Under their influence, the term “comorbidity” arose many synonyms, among which the most prominent are “polymorbidity”, “multimorbidity”, “multifactorial diseases”, “polypathy”, “soreness”, “dual diagnosis”, “pluripathology”, etc. Thanks to the work done, the causes of comorbidity have become clear to some extent: anatomical proximity, a single pathogenetic mechanism, cause-and-effect relationship and complication. However, despite the abundance of definitions and synonyms, there is no unified classification and generally accepted terminology of comorbidity today.

Some authors contrast the concepts of comorbidity and multimorbidity with each other, defining the first as the multiple presence of diseases associated with a proven single pathogenetic mechanism, and the second as the presence of multiple diseases not related to each other by currently proven pathogenetic mechanisms. Others argue that multimorbidity is a combination of many chronic or acute diseases and medical conditions in one person, and do not emphasize the unity or difference of their pathogenesis. However, a fundamental clarification of the term “comorbidity” was given by H. C. Kraemer and M. van den Akker, defining it as a combination of several, namely chronic, diseases in one patient. They also proposed the first classification of comorbidity. According to their data, factors influencing the development of comorbidity may include chronic infection, inflammation, involutory and systemic metabolic changes, iatrogeny, social status, environmental conditions and genetic predisposition.

Causal comorbidity caused by parallel damage to various organs and systems, which is caused by a single pathological agent, for example, alcoholic visceropathy in patients with chronic alcohol intoxication, pathology associated with smoking, or systemic damage due to collagenosis.

Complicated comorbidity is the result of the underlying disease and usually consistently manifests itself in the form of target organ damage some time after its destabilization. Examples of this type of comorbidity are chronic renal failure due to diabetic nephropathy in patients with type 2 diabetes mellitus or the development of cerebral infarction as a result of a complicated hypertensive crisis in patients with essential hypertension.

Iatrogenic comorbidity manifests itself when a doctor has a forced negative impact on a patient, subject to the pre-established danger of a particular medical procedure. Glucocorticosteroid osteoporosis is widely known in patients receiving systemic hormone therapy for a long time, as well as drug-induced hepatitis as a result of chemoprophylaxis of pulmonary tuberculosis prescribed due to changes in tuberculin tests.

Unspecified comorbidity assumes the presence of common pathogenetic mechanisms for the development of diseases that make up this combination, but requires a number of studies to confirm the hypothesis of the researcher or clinician. Examples of this type of comorbidity are the development of erectile dysfunction in patients with atherosclerosis and arterial hypertension, as well as the occurrence of erosive and ulcerative lesions of the mucous membrane of the upper gastrointestinal tract in “vascular” patients.

An example of a so-called “random” type of comorbidity is a combination of coronary heart disease (CHD) and cholelithiasis, or a combination of acquired heart disease and psoriasis. However, the “randomness” and apparent illogicality of these combinations can soon be explained from a clinical and scientific point of view.

Comorbidity as the coexistence of two and/or more syndromes or diseases, pathogenetically interrelated or coinciding in time in one patient, regardless of the activity of each of them, is widely represented among patients hospitalized in therapeutic hospitals. In primary care, patients with multiple medical conditions are the rule rather than the exception. According to M. Fortin, based on an analysis of 980 case histories taken from the daily practice of a family doctor, the prevalence of comorbidity ranges from 69% in young patients (18-44 years old) to 93% among middle-aged people (45-64 years old) and up to 98% - in patients of the older age group (over 65 years). Moreover, the number of chronic diseases varies from 2.8 in young patients to 6.4 in old people. In this work, the author points out that fundamental studies of medical documentation aimed at studying the prevalence of comorbidity and identifying its structure were carried out before the 1990s. Noteworthy are the sources of information used by researchers and scientists dealing with the problem of comorbidity. They were medical histories, outpatient records of patients and other medical documentation available from family doctors, insurance companies and even in the archives of nursing homes. The listed methods for obtaining medical information were mostly based on the clinical experience and qualifications of clinicians who made clinically, instrumentally and laboratory confirmed diagnoses for patients. That is why, despite their unconditional competence, they were very subjective. It is surprising that none of the comorbidity studies performed analyzed the results of pathological autopsies of deceased patients, which would be very important. “The duty of doctors is to open the person they treated,” Professor Mudrov once said. Autopsy allows us to reliably establish the structure of comorbidity and the immediate cause of death of each patient, regardless of his age, sex and gender characteristics. Statistical data on comorbid pathology, based on these sections, are largely devoid of subjectivity.

Prevention and treatment of chronic diseases are designated by the World Health Organization as a priority project of the second decade of the 21st century, aimed at improving the quality of life of the world population. This determines the widespread tendency to conduct large-scale epidemiological studies in various fields of medicine, carried out using serious statistical calculations.

An analysis of a ten-year Australian study of patients with six common chronic diseases found that about half of older patients with arthritis had hypertension, 20% had cardiovascular disease, and 14% had type 2 diabetes. More than 60% of patients with bronchial asthma indicated concomitant arthritis, 20% - cardiovascular diseases and 16% - type 2 diabetes mellitus. Elderly patients with chronic renal failure had a 22% higher incidence of coronary artery disease and a 3.4-fold higher incidence of new coronary events compared with patients without renal impairment. With the development of end-stage renal failure requiring replacement therapy, the incidence of chronic forms of ischemic heart disease is 24.8%, and myocardial infarction is 8.7%. The number of comorbid diseases increases significantly with age. Comorbidity increases from 10% in people under 19 years of age to 80% in people 80 years of age and older.

A Canadian study of 483 obese patients found that the prevalence of obesity-related comorbidities was higher among women than men. The researchers found that about 75% of obese patients had comorbidities, which in most cases were dyslipidemia, hypertension and type 2 diabetes. It is noteworthy that among young obese patients (from 18 to 29 years old), 22% of men and 43% of women had more than two chronic diseases.

According to our data, based on materials from more than three thousand pathological sections (n = 3239) of patients with somatic pathology admitted to a multidisciplinary hospital for decompensation of a chronic disease (average age 67.8 ± 11.6 years), the comorbidity rate is 94.2% . Most often in a doctor’s work there are combinations of two and three nosologies, but in isolated cases (up to 2.7%) one patient combines up to 6-8 diseases at the same time.

A fourteen-year study of 883 patients with idiopathic thrombocytopenic purpura conducted in the UK showed that the disease is associated with a wide range of somatic pathologies. In the structure of comorbidity of these patients, the most common are malignant neoplasms, diseases of the musculoskeletal system, skin and genitourinary system, as well as hemorrhagic complications and other autoimmune diseases, the risk of developing which within five years from the onset of the underlying disease exceeds 5%.

The study, conducted in the United States, included 196 patients with laryngeal cancer. This work showed that the survival of patients with different stages of laryngeal cancer varies depending on the presence or absence of comorbidity. At the first stage of cancer, survival is 17% in the presence of comorbidity and 83% in its absence, in the second stage it is 14% and 76%, in the third stage it is 28% and 66%, and in the fourth stage it is 0% and 50%, respectively. In general, the survival rate of comorbid patients with laryngeal cancer is 59% lower than the survival rate of patients without comorbidity.

As can be seen from recent works, in addition to therapists and general practitioners, narrow specialists also often encounter the problem of comorbidity. Unfortunately, they extremely rarely pay attention to the coexistence of a whole spectrum of diseases in one patient and primarily treat a specialized disease. In current practice, urologists, gynecologists, otorhinolaryngologists, ophthalmologists, surgeons and other specialists often include only “their” disease in the diagnosis, leaving the search for concomitant pathology to other specialists. The unspoken rule of any specialized department has become the advisory work of the therapist, who takes upon himself the syndromic analysis of the patient, as well as the formation of a diagnostic and treatment concept that takes into account the patient’s potential risks and his long-term prognosis.

Thus, the influence of comorbid pathology on clinical manifestations, diagnosis, prognosis and treatment of many diseases is multifaceted and individual. The interaction of diseases, age and drug pathomorphism significantly changes the clinical picture and course of the main nosology, the nature and severity of complications, worsens the patient’s quality of life, and limits or complicates the diagnostic and treatment process.

Comorbidity affects the prognosis for life and increases the likelihood of death. The presence of comorbid diseases contributes to an increase in bed days, disability, interferes with rehabilitation, increases the number of complications after surgical interventions, and increases the likelihood of falls in elderly patients.

However, in the majority of randomized clinical trials conducted, the authors included patients with a separate refined pathology, making comorbidity an exclusion criterion. That is why the listed studies, devoted to assessing the combination of certain individual diseases, are difficult to classify as works studying comorbidity in general. The lack of a unified, comprehensive scientific approach to assessing comorbidity leads to gaps in clinical practice. The absence of comorbidity in the taxonomy of diseases presented in the International Classification of Diseases, X Revision (ICD-10) cannot go unnoticed. This fact alone provides the basis for the further development of a general classification of diseases.

Despite the many unsolved patterns of comorbidity, the lack of its unified terminology and the ongoing search for new combinations of diseases, based on the available clinical and scientific data, we can conclude that comorbidity is characterized by a range of undoubted properties that characterize it as a heterogeneous, frequently occurring phenomenon that increases the severity of the condition and worsens the prognosis of patients. The heterogeneity of comorbidity is due to a wide range of causes that cause it.

There are a number of rules for formulating a clinical diagnosis for a comorbid patient that should be followed by a practicing physician. The basic rule is to distinguish in the structure of the diagnosis the main and background diseases, as well as their complications and concomitant pathologies.

If a patient suffers from many diseases, then one of them is the main one. This is the nosological form that itself or as a result of complications causes a priority need for treatment at a given time due to the greatest threat to life and ability to work. The underlying disease itself or through complications can cause death. The main disease is the reason for seeking medical help. As the examination progresses, the diagnosis of the least prognostically favorable disease becomes the main diagnosis, while other diseases become concomitant.

The underlying cause may be several competing serious diseases. Competing diseases are nosological forms present simultaneously in the patient, mutually independent in etiology and pathogenesis, but equally meeting the criteria of the underlying disease.

The background disease contributes to the occurrence or unfavorable course of the underlying disease, increases its danger, and contributes to the development of complications. This disease, like the main one, requires immediate treatment.

All complications are pathogenetically related to the underlying disease; they contribute to an unfavorable outcome of the disease, causing a sharp deterioration in the patient’s condition. They belong to the category of complicated comorbidity. In some cases, complications of the underlying disease, associated with it by a common etiological and pathogenetic factors, are designated as concomitant diseases. In this case, they must be classified as causal comorbidity. Complications are listed in descending order of prognostic or disabling significance.

The remaining diseases present in the patient are listed in order of importance. The concomitant disease is not etiologically or pathogenetically related to the main disease and is considered to not significantly affect its course.

The presence of comorbidity should be taken into account when choosing a diagnostic algorithm and treatment regimen for a particular disease. For this category of patients, it is necessary to clarify the degree of functional disorders and morphological status of all identified nosological forms. Whenever a new symptom, including a mild one, appears, a comprehensive examination should be carried out to determine its cause. It is also necessary to remember that comorbidity leads to polypharmacy, i.e. the simultaneous prescription of a large number of drugs, which makes it impossible to control the effectiveness of therapy, increases the material costs of patients, and therefore reduces their compliance (adherence to treatment). In addition, polypharmacy, especially in elderly and senile patients, contributes to a sharp increase in the likelihood of developing local and systemic unwanted side effects of drugs. These side effects are not always taken into account by doctors, since they are regarded as a manifestation of one of the comorbidity factors and entail the prescription of even more medications, closing a “vicious circle.”

Simultaneous treatment of several diseases requires strict consideration of the compatibility of drugs and thorough adherence to the rules of rational pharmacotherapy, based on the postulates of E. M. Tareev “Every non-indicated drug is contraindicated” and B. E. Votchal “If a drug has no side effects, you should think about whether it has any effects at all."

« A specialist is like gumboil - its completeness is one-sided“- a group of authors once wrote under the pseudonym Kozma Prutkov (yeah, for those who didn’t know - K. Prutkov is not a real person who once lived on our land), and therefore today the question of conducting a generalizing fundamental study of comorbidity, its properties and patterns, as well as phenomena and events associated with it - studies at the patient’s bedside and at the dissecting table. The result of this work should be the creation of a universal tool that allows a practitioner to easily and unburdenedly assess the structure, severity and possible consequences of comorbidity, conduct a targeted examination of patients and prescribe adequate treatment for them.

Comorbidity is the simultaneous occurrence of different diseases or pathological conditions in a patient.
This is the only common place for the whole variety of interpretations of K., if you try to generalize them.

Synonym (more precisely, in Russian): comorbidity.

"TO. – coexistence of two and/or more syndromes (transsyndromal K.) or diseases (transnosological) in one patient, pathogenetically interrelated or coinciding in time (chronological).”
- (if they did not coincide in time, the word “coexistence” would be inappropriate. It is remarkable that the author specifies: “in one patient” (!). It is also strange that he did not decorate his definition with the term “pathogenetic K.” in parentheses... The prefix "trans" suggests something more than co-occurrence).
. "TO. - a combination of two or more independent diseases or syndromes, none of which is a complication of the other, if the frequency of this combination exceeds the probability of a random coincidence.”
- (for A. Fainstein, both complications and pregnancy are suitable).
"TO. may be associated with a single cause or common mechanisms of pathogenesis these states but sometimes explained by similarity their clinical manifestations, which does not allow one to clearly differentiate them from each other. An example is atherosclerosis and hypertension.”
- (simply read like this: “may be connected, or maybe not connected - this is unknown to science”!).

The phrase that completes this confusion: “So, comorbidity is not an artifact, an atypical phenomenon or a certain myth and fashion.<…>K. is a clinical reality...", you need to read exactly the opposite, because there is no greater artifact than the so-called. "clinical reality". And there is no doubt that K. has become fashionable - 500,000 finds on the Internet in Russian; more than 3.5 million in English.

When you read that “K. heterogeneous (random, causal, complicated, unspecified)”; “transindromal, transnosological, chronological; has “three different subtypes: pathogenetic, diagnostic and prognostic...”, etc. etc., you understand that a medical institute is not the best forge of scientific personnel... You can still see the same “clinical mess” in people’s heads (see Medical classifications), which is also supported by Wikipedia, supplementing the collection supposedly with “Synonyms of K.” ™:

multimorbidity;
multimorbidity;
multifactorial diseases;
polypathy;
sympathy;
dual diagnosis (why not triple? Not quadruple?);
pluripathology.

It has reached the point of complete clinical nonsense. Complications of the underlying disease caused by a doctor in a patient began to be called “iatrogenic comorbidity” (exactly like theft - "misuse of funds"...). And finally, K. herself is announced "new pathology". “New” – that is, until 2013, patients had “concomitant diseases”, and now (thanks to A. Fainstein or A.L. Vertkin?) – a new pathology!

Just one thing, gentlemen, comrades! Either “comorbidity” is a term for a combination of pathologies, or the pathology itself. Reading this, you begin to think that it is a “new pathology” exclusively of the authors’ thinking.

It is interesting that many Russian articles on the topic begin with a proclamation of a certain unity of the organism (here are Plato, and Hippocrates, and S.P. Botkin, and G.A. Zakharyin, and whoever else can be remembered!), and end with the definition of this unity dividing. The coexistence of something presupposes the presence of two or more units (pieces) of this “something”... That is, in essence K. differs little from banal nosological views:
1st nosology + 2nd nosology = comorbidity!
This is its methodological primitivism, so attracting “scientific” clinicians who are practicing in assigning new Greek, Latin and English prefixes and roots to the “new clinical entity”!

What is this

Definition of comorbidity as coexistence of several diseases refers us to ideas about them as Kant’s “Things-in-themselves” (existing outside our consciousness), that is, “really”, which “settle” in our body separately... And the term K., as it were, is a flirtatious smile at the times when the body was considered as a kind of integrity, instead of which there will now be a “piece of the body” populated, for example, by two or three diseases.

Since every year (we live in difficult times!), as well as with the age of the patient, K. grows, it remains to wait for the whole organism to become “comorbid.” Obviously, this is guaranteed to happen before death, and finally (!), the entire organism will be sick, and you can begin to treat the patient, and not the disease (as the great classics bequeathed)...

It is also unclear why the authors of the article about K. on Wikipedia believe that “...a fundamental clarification of the term was given by H.C. Kraemer and M. van den Akker, defining comorbidity as a combination in one patient of two and/or more chronic diseases pathogenetically interrelated or coinciding in time in one patient, regardless of the activity of each of them.”

Term, which in theory should stand for something one, denotes two concepts separated by a union "or"… (“Are you married or a spinster?” - “Neither this nor that! Hee-hee-hee...").

So is it a common pathogenesis or a simple coincidence in time? If both, why is it called “clarification” and even “fundamental”, for how, besides the word “chronic,” does this differ from the definition of A. Feinstein himself? Finally, all chronic diseases were once acute/subacute. So at this stage we can’t talk about K.? And generally speaking, Why it is important?

And if they have a common pathogenesis (that is, it would seem, suggesting a single pathogenetic treatment), it is unclear how the ideologists of the topic everywhere talk about necessity with K. combined, multidrug therapy. That is, the head and ass of the worm from the epigraph to this article receive different treatment! Or vice versa: if this one worm, why do the head and ass have different names? And finally, if diseases (the worm) are viewed as a continuum of conditions, then how can many drugs be used simultaneously, rather than sequentially, as one moves along the continuum? The above is evidence of the view of K. as a simple set of diseases.

Since doctors who think of the body as a certain integrity, with rare exceptions, are hard to find these days, everyone likes comorbid diseases in the post-Feinstein reading. We still have 2-3-4, etc. with existing diseases. This allows you to think less and treat according to the cookbooks of the pharmaceutical industry, according to the principle “for every disease there is its own medicine.” This “understanding” of the integrity of the body is cultivated by pharmaceutical companies to expand their sales (we say K., we mean polypharmacy). This is what you hear: “When purchasing this drug, they usually also take these medications”...

All because this damn “index disease” is not properly translated into Russian anywhere and, more importantly, nowhere not explained and it hypnotizes the public. Perhaps it should be meaningfully translated as “indicating illness”? Showing us the path of therapy or knowledge? Guiding disease! Or is it still a primarily identified disease? All definitions of K. “from A. Feinstein” and their interpretations either imply or directly speak about this main (main, core, leading, etc.) disease. At the same time, the presence of, excuse the expression, “index disease” is stated as something self-evident, and how it was formed is, no matter how inconveniently, asked in polite society...

Who and how determines which disease will be the main one? Is this a convention or not? The disease that started earlier or was discovered first? But then what is the role of chance in making a “main” diagnosis? Did the patient see a specialist for the “main disease”? Or did you complain about something in the first place? Is this the disease the researcher is studying? Or maybe the ICD or DSM “tells” us to identify the main disease, and then the accompanying one? As for the rest, is it a matter of taste?

The “primary” nature of the diagnosis may also depend on the time it was carried out: if you caught a disease at a late stage - one main disease, at an earlier stage - “another”.

How is the subordination of the main and secondary diseases expressed? What exactly meaning this main disease? Can K. develop into multimorbidity (see below)? All these issues are practically not discussed and, certainly, not resolved, either by Feinstein himself or his followers.

The “main disease,” which for some reason became the inviolable sacred cow of K.’s theory, apparently bothered not only me. They tried to get rid of her.

The emergence of multimorbidity. What kind of animal?

They came up with the idea of distinguishing comorbidity from multimorbidity (MM), which was also offered to us at the same time as a synonym for K!

Don't try to understand why comorbidity decided to separate from multimorbidity. Here it’s like in a joke, but about a Russian language lesson in a Georgian school: “Deti, in Russian, fork and plate are written without a soft sign, and salt and beans are written vice versa. Remember this kids because it is impossible to understand this!».

There is even an international scientific society of multimorbidity ("IRCM" - International Research Community on Multimorbidity). Don't expect (like I did) that you'll find a definition of MM on the first page of their website! No. There is not even a clear explanation of when this community arose! But there is a list of theoretical works, in which chronologically the first is an article that says: “In view of the ambiguity of the term, we propose to distinguish between K., based on the “classical” definition (the assumption of a certain main, “index” disease) and multimorbidity, meaning any co-occurrence of medical conditions in a subject”.
There is a note on the site by Martin Fortin, from which it follows that colleagues at IRCM have created a community, but have not yet decided what they will consider MM, since they are confused in the definitions and are offering everyone who wants to help them figure it out , answering the question: “How should MM be determined?”. Answers are offered, as in the Unified State Exam:

multiple concurrent chronic or long-term diseases or conditions, none of which is considered an index disease;
several concomitant diseases or conditions, none of which is considered as a leading disease (index Disease);
any of the above definitions;
other definition (please provide definition or link)

In this surprisingly rich variety of answers, the second “definition” simply lacks the word “chronic or long-term.” Is all the cheese coming out due to chronification or duration?

Confusion with K. and MM. trivial mistakes also make matters worse. In the 2014 article, when the authors, as usual, set out “in their own words” what was written by van den Akker and A. Fainstein, the latter, having mixed up the references, attributed the term “MM” and “clarified” (p. 363) what is its basis, in contrast from K., “...it is not the disease that lies, but a specific patient...” (that is, not sour, but round...). A complete bullshit paragraph. In a word, another exegesis of A. Fainstein and other muddy texts.

And here is another treasure trove of wisdom, a certain medical reference book by F.I. Belyalov. :

Comorbidity is the presence of another disease or medical condition at the same time as the present disease. Multimorbidity is a combination of many chronic or acute diseases and medical conditions in one person (National Library of Medicine).

100 1000 rubles to the one who finds the difference. Does the first definition mean two or three people, not one?

Total

Summarizing what has been written, it is clear that the authors of different definitions of K. and CC, in the process of pounding the waters in the mortar of clarifications of these concepts, focus either on the presence of a “main” disease, or on the chronification of the process, or on the general pathogenesis (risk factors, etc. ) sometimes in the absence/presence of all of the above, sometimes they include “non-diseases”, sometimes not, etc. and so on. Only one Oblomov question remains open - For what?

It’s certainly not K. Feinstein’s fault for this. It’s impossible to get rid of the feeling that he just moved their "followers" rewrite in some places traditional medicine “into the language of K.” The fact itself untranslated term, its use in the Cyrillic version is already a claim to the presence of some other meaning in it. Say: “comorbidity” and the scientific bubble will immediately burst! There's been a change language, to denote previously known by others names.

Some examples of language transformation

In the form of Russian terms of Feinstein's followers.

Previous, normal name	Current name	Comment (mine, NZ)
Concomitant disease	Comorbid disease	"Cyrillization" instead of translation
Pregnancy (diet, etc.) against the background of Disease	Comorbid condition	Terminological pathologization of the norm
Complications of the underlying disease as a result of medical error/negligence of intervention	Iatrogenic comorbidity	“Taught” embellishment, with its “detachment”, as if removing part of the guilt from the doctor; (compare: theft - misuse of funds)
Differential diagnosis of concomitant diseases	Differential diagnosis of comorbidity	Untranslated term - "Cyrillization"
Diagnostic error	“Intellectual influence on diagnostics” (F.’s own expression “)	This is not your visit to Pronka...

We must admit that:

The current definitions of both “K” and “MM” mean completely different things. The only thing they have in common is the fact that diseases occur together.
Term "K". in the author's version it is unsuccessful from a linguistic point of view, since it pathologizes the norm.
In any case, the term K itself, both in its original, Feinsteinian sense, and in its interpretations does not indicate any qualitatively new integrity.
Term "K". has gone beyond the “Feinsteinian” epidemiological meaning and it will now be very difficult to stop its confusing use in other contexts.

Using the example of the history of the term K, one can see how human consciousness is frantically trying to break out of the archetypal opposition Health/Disease, expressed in terms of the “struggle between Good and Evil.” They came up with MM, where (like social development) all diseases acquire “democratic equality”, overthrowing the monarchy in the person of the Main Disease. But understanding them interactions within these views impossible, since the diseases still exist separately.

It seems that many doctors and researchers were so drawn to K.’s theory because, with varying degrees of awareness, they were interested in interaction(if this word is even appropriate) of “different” diseases, and not the very fact of their joint occurrence. However, this immediately destroys the concept of nosological form and returns us “to the origins” - to the patient.

Sometimes you wonder how the ideas of the existence of individual diseases are so tenacious, when all-pervading systems have long been discovered: blood circulation, lymph circulation, hormonal, immune, connective tissue, finally, etc.?

46 years have passed since the introduction of the term K. The Internet, the desktop computer, appeared; an ebonite rotary telephone and a TV with a kinescope were replaced by iPads and iPhones, but doctors like “I-hurt” remained with comorbidity from A. Fainstein... Let's take a look at what they write about K. today.

Well made epidemiological works of the XXI century, e.g., 2012, this is, as Feinstein intended– another study of the co-occurrence of diseases in a particular population, of which tens of thousands have already been done. They are studied by clinical epidemiologists. Their recommendations, most suitable for healthcare organization, they simply geographically localize more and more new data on co-morbidity, and their conclusions are not God knows how complex.

Numerous attempts to directly adapt such data to the treatment process of specific patients usually end in complete failure. In articles from the 2000s. recommendations (or rather, slogans) are as general and banal as they are nonspecific.

What do professors, whose life (like the life of V.S. Chernomyrdin) “...passed in an atmosphere of comorbidity,” tell practical doctors? Here are some thoughtful recommendations-slogans, obviously selected over many years of “scientific work” (A.L. Vertkin, N.O. Khovasova). After establishing the fact of an increase in age-related K. and the already sore percentages of their joint occurrence, we read the conclusions and recommendations:

“So, the presence of comorbidity should be taken into account when choosing a diagnostic algorithm and treatment regimen for a particular disease. For this category of patients, it is necessary to clarify the degree of functional disorders and morphological status of all identified nosological forms. With the appearance of each new one, incl. If a symptom is mild, a comprehensive examination should be carried out to determine its cause.<….>“In addition to the clinical significance of comorbidity, it is necessary not to forget about the economic component...” (very important for a polyclinic therapist! NZ)… <…>“Thus, risk factors, polymorphism of the clinical picture, multiple organ lesions, drug polypharmacy (Sic! N.Z.)“These are the key links that must be taken into account when providing care to a patient with comorbid pathology.”

The article also highlights as NB! following: “Risk factors in Russia must be considered as diseases that need to be treated!”<…>“Risk factors, polymorphism of the clinical picture, multiple organ lesions, drug polypharmacy - these are the key links that must be taken into account when providing care to a patient with comorbid pathology.”

Reading this, you immediately understand that now things will work out for us!

Afterword

Concluding our consideration of the “era of “K” by A. Feinstein,” we note that the author of the term K. did not pretend to study the mutual influence of diseases (mechanisms of pathogenesis, etc.) and did not do this, he only stated this possibility. Let us thank him for pointing out the importance of the co-occurrence of diseases (which was known before him) and let us now turn to consideration interaction that today we still called separate diseases.

From the point of view medicine, and also for scientific construction of general human pathology, talking about the joint occurrence of diseases, etc., makes sense only if they are united by something else other than the very fact of their occurrence in the human body (for where else can they occur?). As a matter of fact, it is their meeting in one body that marks their commonality (etiological, pathogenetic, or some other).

Looking ahead I will say that if there is no commonality, then such diseases do not occur in the same body! This phenomenon, thanks to the dominance and fetishization of the term by A. Feinstein, was extremely unfortunately called “reverse K.” or more adequately – dystropia . Why was it unsuccessful? Well, it’s like in the opposition love/hate, calling the latter “reverse love”...

That is, at first they fucked up everyone’s brains and confused everyone with the concept of K., and then they were forced to start from this name in order to express something from it, K. different...
It turns out that there were times “before the birth of A. Feinstein” (Before the Russian Federation), when the problem of the co-occurrence of diseases was considered much more progressively than after he invented the so-loved term K.

Comorbidity was studied in parallel by completely different people who opened the era of Integral Medicine.

Home reading

Censored version of this article, published in the journal Plastic Surgery and Cosmetology, August 2016.

Professor M. Ya. Mudrov(assembly speech “A speech on the way to teach and learn practical medicine or active medical art at the bedside of the sick,” 1820)

Part 2. read in No. 6, 2013.

Thus, the significance of comorbidity is beyond doubt, but how can it be measured in a specific patient, for example, in patient S., 73 years old, who called an ambulance due to sudden pressing pain in the chest? From the anamnesis it is known that the patient has suffered from coronary artery disease for many years. She had experienced similar pain in the chest before, but always went away within a few minutes after taking sublingual organic nitrates. In this case, taking three nitroglycerin tablets did not produce an analgesic effect. From the anamnesis it is known that the patient suffered myocardial infarction twice over the past ten years, as well as acute cerebrovascular accident with left-sided hemiplegia more than 15 years ago. In addition, the patient suffers from hypertension, type 2 diabetes mellitus with diabetic nephropathy, uterine fibroids, cholelithiasis, osteoporosis and varicose veins of the legs. It was possible to find out that the patient regularly takes a number of antihypertensive drugs, diuretics and oral hypoglycemic agents, as well as statins, antiplatelet agents and nootropics. In the past, the patient underwent cholecystectomy for cholelithiasis more than 20 years ago, as well as lens extraction for cataracts in the right eye 4 years ago. The patient was hospitalized in the cardiac intensive care unit of a multidisciplinary hospital with a diagnosis of acute transmural myocardial infarction. The examination revealed moderate azotemia, mild hypochromic anemia, proteinuria and a decrease in left ventricular ejection fraction.

There are currently 12 generally accepted methods for measuring comorbidity. The first methods for assessing comorbidity were the CIRS (Cumulative Illness Rating Scale) system and the Kaplan-Feinstein index, developed in 1968 and 1974. respectively. The CIRS system, proposed by B. S. Linn, was a revolutionary discovery, as it enabled practitioners to assess the number and severity of chronic diseases in the structure of the comorbid status of their patients. However, it did not take into account the age of patients and the specifics of diseases of old age, and therefore 23 years later it was revised by M. D. Miller. A variation of the CIRS system in elderly patients is called CIRS-G (Cumulative Illness Rating Scale for Geriatrics).

Correct use of the CIRS system implies a separate summary assessment of the condition of each organ system: “0” corresponds to the absence of diseases of the selected system, “1” - mild deviations from the norm or previous diseases, “2” - a disease requiring drug therapy, “ 3" - a disease that has caused disability, and "4" - severe organ failure requiring emergency treatment. The CIRS system evaluates comorbidity by a score that can vary from 0 to 56. According to its developers, maximum results are not compatible with the life of patients. An example of comorbidity assessment is presented in Table. 1.

Thus, the comorbidity of patient S., 73 years old, can be regarded as moderate (23 points out of 56), however, it is not possible to assess the patient’s prognosis due to the lack of interpretation of the results obtained and their connection with a number of prognostic characteristics.

The Kaplan-Feinstein Index was created by examining the impact of comorbidities on 5-year survival in patients with type 2 diabetes. In this comorbidity assessment system, all existing diseases and their complications, depending on the severity of organ damage, are classified into mild, moderate and severe. In this case, the conclusion about total comorbidity is made on the basis of the most decompensated organ system. This index provides a summary, but less detailed than the CIRS system, assessment of the condition of each organ system: “0” - absence of disease, “1” - mild disease, “2” - moderate disease, “3” - severe disease. The Kaplan-Feinstein index evaluates comorbidity using a score that can vary from 0 to 36. An example of comorbidity assessment is presented in Table. 2.

Thus, the comorbidity of patient S., 73 years old, can be regarded as moderate (16 points out of 36), but its prognostic significance is again unclear due to the lack of interpretation of the total score obtained by summing up the diseases the patient has. In addition, the obvious disadvantage of this method of assessing comorbidity is the excessive generalization of nosologies and the absence of a large number of diseases on the scale, which should probably be noted in the “miscellaneous” column, which reduces the objectivity and effectiveness of this method. However, the undeniable advantage of the Kaplan-Feinstein index over the CIRS system is the possibility of independent analysis of malignant neoplasms and their severity.

Among the comorbidity assessment systems existing today, the most common are the ICED scale and the Charlson index, proposed to assess the long-term prognosis of patients in 1987 by Professor Mary Charlson.

This index is a scoring system (from 0 to 40) for the presence of certain concomitant diseases and is used to predict mortality. When calculating it, the points corresponding to concomitant diseases are summed up, and one point is added for every ten years of life when the patient exceeds forty years of age (i.e. 50 years - 1 point, 60 years - 2 points) (Table 3).

Thus, the comorbidity of patient S., 73 years old, according to this method corresponds to a mild degree (9 points out of 40). The main distinctive feature and unconditional advantage of the Charlson index is the ability to assess the patient’s age and determine the mortality of patients, which in the absence of comorbidity is 12%, with 1-2 points - 26%; with 3-4 points - 52%, and with a total of more than 5 points - 85%. Unfortunately, the presented method has some drawbacks: when calculating comorbidity, the severity of many diseases is not taken into account, and a number of prognostically important diseases are also missing. In addition, it is doubtful that the theoretically possible prognosis of a patient suffering from bronchial asthma and chronic leukemia is comparable to the prognosis of a patient with myocardial infarction and cerebral infarction. Some of the indicated shortcomings of the Charlson index were corrected by R. A. Deyo in 1992. Chronic forms of coronary heart disease and stages of chronic heart failure were added to the modified Charlson index.

The ICED (Index of Co-Existent Disease) index was originally developed by S. Greenfield to assess the comorbidity of patients with malignant neoplasms, and subsequently found application in other categories of patients. This method helps in calculating the length of hospital stay and the risk of readmission of a patient after surgery. To calculate comorbidity, the ICED scale proposes to evaluate the patient’s condition separately according to two components: physiological and functional characteristics. The first component includes 19 comorbidities, each of which is rated on a 4-point scale, where “0” is the absence of the disease and “3” is its severe form. The second component assesses the impact of comorbidities on the patient's physical condition. It rates 11 physical functions on a 3-point scale, where “0” is normal function and “2” is impossible to perform.

Having analyzed the comorbid status of patient S., 73 years old, using the most popular international scales for assessing comorbidity, we obtained fundamentally different results. Their ambiguity and inconsistency to a certain extent complicated our judgment about the true severity of the patient’s condition and complicated the prescription of rational pharmacotherapy for her diseases. Every clinician, regardless of clinical experience and knowledge of medical science, faces such challenges every day. Moreover, in addition to the comorbidity assessment systems discussed in this article, there are currently the GIC index (Geriatric Index of Comorbidity, 2002), the FCI index (Functional Comorbidity Index, 2005), the TIBI index (Total Illness Burden Index, 2009), as well as a number scales that allow patients to independently assess their comorbidity. Analysis of the patient's concomitant pathology in the same clinical case using these indices would undoubtedly give new results, but would also confuse the practitioner even more.

It seems to the authors that the main obstacles to the implementation of comorbidity assessment systems in the diverse treatment and diagnostic process are their fragmentation and narrow focus. Despite the variety of methods for assessing comorbidity, the lack of a single generally accepted way of measuring it, devoid of the shortcomings of existing methods, is of concern. The lack of a single tool created on the basis of enormous international experience, as well as the methodology for its use, does not allow comorbidity to “turn its face” to a practicing physician. At the same time, due to disparate approaches to the analysis of comorbid status and the absence of comorbidity components in the curricula of medical universities, its prognostic impact is not obvious to the clinician, which makes publicly available systems for assessing comorbidity unreasonable and therefore unclaimed.

“A specialist is like a gumboil - its completeness is one-sided,” a group of authors once wrote under the pseudonym Kozma Prutkov, and therefore today the question has arisen of conducting a generalizing fundamental study of comorbidity, its properties and patterns, as well as the phenomena and phenomena associated with it - bedside research the patient and at the section table. The result of this work should be the creation of a universal tool that allows a practitioner to easily and unburdenedly assess the structure, severity and possible consequences of comorbidity, conduct a targeted examination of patients and prescribe adequate treatment for them.

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A. L. Vertkin,Doctor of Medical Sciences, Professor
A. S. Skotnikov 1,Candidate of Medical Sciences

Many interesting and unusual terms are known in different areas of human activity. Many of them are well-known, but most people have never even heard of some. For example,comorbidity. This is a medical term that denotes a very interesting field of professional diagnostics and therapy.

History of the term

If you follow the path of a clear professional dictionary, then in medicine there is a term that denotes a set of diseases according to certain characteristics - comorbidity. This definition, traditional for medicine, has its roots in the Latin language. It is from this that two components are taken - coniunctim And morbus - “together” and “disease”, which became the basis of a term unusual for the common man, denoting a complex of chronic diseases in one patient, interconnected in some certain way.

This definition of the patient’s condition has been considered since ancient times, at the dawn of the emergence of healing diseases. Both the ancient Greeks and the healers of the Ancient East treated not the disease itself, as something isolated, but the entire body suffering from the manifestation of a specific illness. Doctors of different generations spoke about the relationship between several problems in a person’s health, manifested by certain symptoms, and, therefore, about the treatment of a whole complex of diseases. And to date, comorbidity is a clinically proven method for making an adequate diagnosis and competent treatment, which helps maintain health.

The term “comorbidity” itself was proposed in 1970 by the American epidemiologist and researcher Alvan R. Feinstein (A.R. Feinstein). At first, this concept was used mainly in clinical epidemiology, but over time it became the main research methodology in various branches of medicine.

Combination of diseases

When visiting a doctor about a specific health problem, a person most often does not suspect that his condition is caused not by one, but by a whole complex of problems. And for many specialists, when making an adequate diagnosis, it becomes clear that in a particular case we can talk about comorbidity. But at the same time, for other doctors, the correct direction for diagnosing the disease and prescribing treatment will be multimorbidity, that is, not a combination of diseases at the pathogenetic level, but their presence separately, which gives an overall picture of the patient’s condition at a given point in time.

But meanwhile, for the vast majority of practicing doctors around the world, it is the combined diseases that become the most qualitative definition of diagnosis and treatment. For example,Comorbidity in cardiology takes into account, in addition to the two main problems of the cardiovascular system - arterial hypertension and coronary heart disease - also problems of the respiratory and urinary systems.

What are the reasons?

For medical practice, comorbidity is a combination of several interrelated diseases that a particular person suffers from. PClinical medicine is faced with the peculiarity that when a patient first approaches a specialized medical institution, in the vast majority of registered cases it is about one specific disease for which treatment is prescribed. But in multidisciplinary hospitals, the picture changes radically; the same patients receive a diagnosis of comorbidity, which allows better treatment to be prescribed in accordance with a comprehensive vision of the identified pathologies. This is due to the fact that more careful observation and examination of the patient in different profiles takes into account all aspects on the basis of which we talk about combined diseases:

anatomical feature - diseased organs located close to each other;
a single pathogenetic mechanism for the development of diseases;
diseases have one cause-and-effect relationship and are united by a single time threshold;
one disease “follows” from another as a complication.

Implying that the patient has comorbidity, the specialist bases his opinion on identified or potentially possible factors:

inflammatory process;
genetic predisposition;
infection;
metabolic changes of an involutive or systemic nature;
social status;
ecology of the region of permanent residence;
Iatrogenesis - deterioration of the patient’s condition (physical and/or emotional due to the fault of a medical worker).

How is the problem studied?

At the current stage of development of medicine, as a science in various spheres of life of the human body, the concept of “comorbidity” is a set of diseases interconnected by the pathogenetic mechanism of occurrence, development, and manifestation. Observation of the patient's condition since ancient times allowed doctors to conclude that it is impossible to qualitatively treat only the manifestation of the disease, without eliminating the cause of its occurrence, moreover, the disease often does not arise as a separate lesion of an organ or system. In fact, there are several diseases, and they are interconnected. The most accurate and ancient method of studying this combination is autopsy. It was the postmortem study of the diseases that a person suffered from that made it possible to draw conclusions that many of them occur together, and thus to identify the presence of comorbidity.

How are combined diseases classified?

Comorbid diseases are present in different areas of medicine. And they can be conditionally divided into comorbidity in psychiatry and a combination of clinical internal diseases. Medical scientists study interrelated diseases in two directions:

transsyndromal - syndromes are interconnected by pathogenetic reasons;
transnosological - diseases that the patient has do not have common pathogenetic causes.

It is this division that makes it possible to differentiate the combination of diseases according to common causes or similar clinical manifestations.

Comorbidity is also divided into the following types:

causal;
complicated;
iatrogenic;
unspecified;
“random” comorbidity.

Diagnosis and treatment of a complex of diseases

Comorbidity problems have been studied by medicine from different points of view for many decades. Recently, this issue has been raised again at the highest levels, and potential work is being done to improve diagnostics, treatment methods, and prognosis. World medicine has already developed several methods for measuring comorbidity, each of which works in a specific area. And the main problem is that each such technique can have different results for the same patient. In determining the presence of comorbidity, and therefore predicting mortality or quality of life of a patient, practicing doctors do not have a single tool that uses specific arguments to obtain the most accurate result. That is why all these techniques are little used in practical therapy in various areas.

At the present stage of development of medicine, comorbidity is the field of study of existing diseases in one patient, interrelated causes or symptoms, potentially significant, but little used in practice due to the lack of specific work algorithms.

Comorbid conditions are one of the most pressing problems of modern rheumatology. The emergence of new diagnostic methods contributes to a better understanding of the pathogenetic connections between various pathological processes occurring in the patient’s body. For example, an acceleration in the development and progression of atherosclerotic lesions against the background of chronic inflammation was noted.

Comorbid conditions in patients with rheumatic diseases are quite common (58% of patients with RA have at least one concomitant disease and 25% have several concomitant diseases (Symmons D., 2006).

The presence of comorbid pathology leads to a worsening prognosis, decreased quality of life, increased incidence of complications, and the occurrence of polypharmacy, which results in decreased compliance. In case of comorbid conditions, it is not always possible to follow the recommendations for examining patients and difficulties arise in selecting adequate therapy. For example, according to the COMORA study, annual assessment of risk factors for cardiovascular events was carried out in only 59.4% of patients involved in the study.

All of the above shows the need to pay great attention to comorbid pathology in systemic connective tissue diseases.

In this work, we set a goal to consider, in our opinion, the most relevant comorbid conditions for rheumatic diseases.

Comorbid lesions of the cardiovascular system

The relevance of the problem of damage to the cardiovascular system in rheumatic diseases is due, first of all, to the high prevalence of rheumatic diseases among the general population. With systemic connective tissue diseases, various types of damage to the cardiovascular system are possible.

Damage to the cardiovascular system occupies one of the leading places in the structure of prevalence and mortality in patients with comorbid pathology in rheumatic diseases. Data from different authors comparing the frequency of causes of death in patients with systemic lupus erythematosus (comorbid infections and cardiovascular pathology) are presented in Table 1.

Table 1. Causes of deaths in systemic lupus erythematosus, %

Author	Infections	Cardiovascular pathology
D.Wallace	21	20
S. Rosner	33	3
T. Helve	17	6
V. Ward	22	16
E. Luchikhina	30	20

The prevalence of comorbid damage to the cardiovascular system, according to different authors, varies. Thus, according to the COMORA study, it averaged 6% (from 1% in Morocco to 17% in Hungary). According to the data presented in the study by O.B. Yaremenko “comorbid conditions in rheumatoid arthritis”, pathology of the cardiovascular system ranks first in frequency of occurrence (Table 2).

Table 2. Frequency of comorbid conditions in rheumatoid arthritis

Pathology	Frequency of comorbid conditions in patients with rheumatoid arthritis, %
Of cardio-vascular system	27,1
Gastrointestinal tract	20,6
Endocrine system	18,8
Rheumatological	13,8
Urinary system	9,6
Respiratory system	1,8
Other pathology	8,3

Since chronic inflammation contributes to cardiovascular damage, the European League Against Rheumatism (EULAR) guidelines suggest multiplying the cardiovascular risk by 1.5 for rheumatoid arthritis if 2 of the following 3 criteria are met:

– duration of the disease more than 10 years;

– presence of rheumatoid factor or anticitrullinated antibodies;

– presence of extra-articular manifestations.

The most common risk factors for the development of damage to the cardiovascular system are arterial hypertension and hypercholesterolemia.

The most common comorbid conditions in patients with rheumatoid arthritis were hypertension (83.1%) and coronary heart disease (10.2%).

The existing autoimmune pathology aggravates the course of the underlying disease through the following mechanisms:

– acceleration of the progression of atherosclerotic lesions of the vascular bed;

– primary damage to the cardiovascular system in an autoimmune disease;

– organ damage due to the use of drugs.

Chronic inflammation makes a significant contribution to the progression of atherosclerosis due to overexpression of adhesion molecules (selectins, integrins) and endothelial dysfunction. Factors leading to the development of endothelial dysfunction include smoking, diabetes, arterial hypertension, dyslipidemia, inflammation, menopause, and hyperhomocysteinemia. As a result, endothelial cells lose the ability to secrete nitric oxide in response to stimulating factors, and an imbalance develops between vasoconstrictor and vasodilator factors.

Several molecular mediators of inflammatory mediators (NF-kB, AP-1, NFAT, STAT) are known that induce expression and RNA. Of particular importance is the nuclear factor NF-kB, which plays an important role in the development of inflammation in rheumatic diseases, as well as in atherosclerotic vascular damage. With the help of NF-B, a wide range of genes involved in the regulation of inflammation are activated.

Heart damage in vasculitis is most often caused by damage to the coronary arteries. In chronic inflammation, an imbalance occurs between pro- and anti-inflammatory cytokines. The result is endothelial dysfunction, manifested by its inability to produce vasodilating agents (eg, nitric oxide).

Patients with concomitant cardiovascular pathology are more likely to experience episodes of silent myocardial ischemia. An attack of angina in such patients often occurs in the form of weakness, shortness of breath, pain in the neck and shoulder. Myocarditis in rheumatoid arthritis is most often detected at the height of the activity of the autoimmune process and does not have specific clinical manifestations. A pathogmonic sign of rheumatoid arthritis are rheumatoid nodules in the myocardium, pericardium and endocardium at the base of the mitral and aortic valves, in the area of the fibrous ring. As a result of the nodule, sclerosis develops, causing the formation of valve insufficiency. In Takayasu arteritis, myocarditis occurs in almost half of the cases.

Usually myocarditis is combined with endocarditis. In most cases, endocarditis proceeds favorably, however, some patients may develop valve defects (usually mitral regurgitation), requiring surgical correction.

In systemic lupus erythematosus, coronary blood flow disturbances, according to scintigraphy, are described in 40% of patients. CRP levels are associated with total coronary risk, carotid IMT thickness, and can be used as a marker of cardiovascular risk in men with SLE. The concentration of soluble TNF-α receptors and pCD40 ligand is interrelated with the presence of atherosclerosis and the thickness of the IMT of the carotid arteries in SLE.

In Takayasu arteritis, damage to the aortic valve, along with aneurysms, retinopathy, and arterial hypertension, is one of the complications that, according to the criteria proposed by K. Ishikawa in 1981, affect the prognosis of the disease.

In the diagnosis of heart damage in systemic vasculitis, not only the collection of complaints and anamnesis, an electrocardiogram, but also imaging methods (ECHO CG) are important. To assess the severity of atherosclerotic lesions, ultrasound of the carotid arteries with assessment of the thickness of the intima-media complex and coronary angiography are used. An echocardiographic study allows one to study the condition of the valve apparatus, pericardium, contractility, etc. However, despite all of the above methods, the main way to verify the diagnosis is myocardial biopsy.

Table 3 presents risk stratification in patients with arterial hypertension.

Table 3. Risk stratification in patients with arterial hypertension

Risk factors, target organ damage and cardiovascular diseases	Blood pressure level (mmHg)
	High normal 130–139/85–89	Arterial hypertension I degree 140–159/90–99	Arterial hypertension II degree 160–179/100–109	Arterial hypertension III degree
No risk factors	Insignificant	Low add. risk	Average extra risk	High add. risk
1–2 risk factors	Low add. risk	Average extra risk	Average extra risk	high add. risk
≥ 3 risk factors, target organ damage, metabolic syndrome or diabetes mellitus	High add. risk	High add. risk	High add. risk	high add. risk
Associated clinical conditions	Very high add. risk	high add. risk	high add. risk	high add. risk

When treating patients with rheumatic diseases, in particular rheumatoid arthritis, it is not advisable to use cyclosporine as a basic therapy due to its ability to increase blood pressure.

In the presence of concomitant cardiovascular pathology in patients with rheumatoid arthritis, it is possible to use methotrexate (recommended together with folic acid), leflunomide, hydroxychloroquine, sulfasalazine (possible use together with methotrexate), TNF-alpha inhibitors. When treating patients with rheumatic diseases, in particular rheumatoid arthritis, it is not advisable to use cyclosporine as a basic therapy due to its ability to increase blood pressure.

Smoking cessation is necessary.

Taking glucocorticoids is recommended in low doses. On the one hand, they inhibit the development of atherosclerosis due to immunosuppression, on the other hand, they have a negative effect on the metabolism of lipids and carbohydrates. Treatment of heart lesions in systemic vasculitis includes not only therapeutic, but also surgical methods (vascular stenting, coronary artery bypass grafting, and valve replacement). Surgical treatment has been shown to improve the prognosis of patients with nonspecific aortoarteritis in the presence of coronary stenosis.

If antihypertensive therapy in the general population is started with an average additional risk, then in patients with a combination of hypertension and an autoimmune disease it should be started at a low additional risk.

The SCORE table is used to estimate the 10-year risk of cardiovascular disease (Table 4).

Table 4. 10-year risk score for cardiovascular disease

Table 4. Frequency of pneumonia among comorbid infections in rheumatic diseases.

Table 6. Frequency of occurrence of different glomerular filtration rates in patients with rheumatoid arthritis of different ages

NOTE

The total risk of cardiovascular complications may be higher than indicated in the table in the following cases:

the patient is approaching the next age category;
presence of signs of asymptomatic atherosclerosis (computed tomography, ultrasound);
cases of early development of cardiovascular diseases in relatives;
decreased HDL cholesterol, increased triglycerides, impaired glucose tolerance, high levels of C-reactive protein, fibrinogen, homocysteine, apolipoprotein B, or lipoprotein(a);
obesity and sedentary lifestyle.

Based on all of the above, the following conclusions can be drawn:

– rheumatoid arthritis is associated with a high cardiovascular risk;

– an annual assessment of the risk of developing cardiovascular diseases is necessary;

– atherosclerosis in patients with rheumatic diseases tends to progress more rapidly than in patients without them;

– strict blood pressure control is required (target levels less than 140/90 mmHg); – control of the lipid spectrum is necessary (LDL level should not be higher than 2.5 mmol/l);

– smoking cessation is necessary.

– regular monitoring of lipid profile (at least once a year)

Comorbid infections

Comorbid infections are one of the main problems of modern rheumatology. The frequency of their occurrence is primarily due to the active use of immunosuppressive therapy. In addition, according to a number of authors, the duration of the disease (> 10 years) is important.

Most often, secondary infections occur in patients with rheumatoid arthritis and systemic lupus erythematosus (38.1% and 19.7% according to the data and 13.2% and 28.4% according to the data, respectively).

Risk factors for the development of comorbid infections in systemic lupus erythematosus are activity, duration, number of exacerbations, lupus nephritis, anemia, leukopenia, high levels of CRP, pulse therapy with glucocorticoids, and the use of cytostatic drugs. In SLE, the incidence of CI has not changed significantly over the past 25 years and ranges from 27 to 55%. Risk factors for the development of comorbid infections in rheumatoid arthritis are: chronic lung diseases, leukopenia, extra-articular manifestations of the disease, severe functional status, the presence of rheumatoid factor, accelerated ESR, and glucocorticoid therapy.

The risk of developing comorbid infections in patients with rheumatoid arthritis increased with the duration of the underlying disease being 10 years or more and the use of glucocorticoids (GCs) as part of combination therapy.

The risk of developing comorbid infections in patients with systemic lupus erythematosus was higher during therapy with glucocorticoids and combined therapy with glucocorticoids and cytostatics (glucocorticoids and cyclophosphamide and glucocorticoids and azathioprine).

The randomized clinical trial EXPLORER showed that patients with systemic lupus erythematosus treated with rituximab were more likely to develop both herpes viral infections in general (15.4 and 8%, respectively) and herpes zoster separately ( 9.55 and 3.4%, respectively), but the differences were not statistically significant. In 2/3 of patients, herpes viral infections regressed within 1 month. . According to a study conducted at the Yaroslavl Medical Academy, comorbid infections occurred in 32.8% of patients (a total of 70 women aged 53 to 79 years were examined). The most common infections were the urinary system (17.1%) and upper respiratory tract (7.1%). Among the etiological factors, bacteria of the genus Klebsiella and fungi of the genus Candida were of greatest importance. S. aureus, Pseudomonas aeroginosa, S. haemoliticus, Morganella morganii were also etiologically significant.

Comorbid infections influence the prognosis of patients with rheumatic diseases. For example, in patients with systemic lupus erythematosus, they are the second most common cause of death.

An important aspect of the fight against comorbid infections is immunization of patients with rheumatic diseases. The EIRA epidemiological study conducted in Sweden showed no increase in the number of cases of onset or exacerbation of rheumatoid arthritis in patients with both positive and negative forms of antibodies to cyclic citrullinated peptide in a 5-year period after immunization.

Comorbid lung lesions

Lung damage in rheumatic diseases is most often associated with immunosuppressive therapy. Representatives of normal microflora (S. рneumoniae, Legionella spp., S. aureus, K. pneumoniae) act as etiological factors. The highest mortality rate is observed in pneumonia caused by Legionella spp, S. aureus, K. pneumoniae. Table 5 shows the frequency of pneumonia among comorbid infections in rheumatic diseases according to data from different authors.

Mortality from pneumonia in patients with rheumatic diseases in general is 11–22%, with systemic lupus erythematosus – 23–27%, with rheumatoid arthritis, mortality from pneumonia was 8–22%, with systemic scleroderma – 12%. The share of pneumonia in the structure of causes of deaths is up to 36%.

According to a study carried out at the Research Institute of Rheumatology of the Russian Academy of Medical Sciences, risk factors for the development of pneumonia in patients with rheumatoid arthritis were:

1) high activity of the inflammatory process;

2) chronic lung diseases;

3) lack of taking basic anti-inflammatory drugs;

4) monotherapy with glucocorticoids.

Moreover, the presence of a combination of factors 1 and 3 increased the risk of developing pneumonia to 19.3%.

Risk factors also include the combined use of glucocorticoids and cytostatics.

The frequency of community-acquired pneumonia in patients with systemic lupus erythematosus is, according to some researchers, 10.3%. The average age of the patients was 38.0±11.5 years, the average duration of SLE at the time of development of pneumonia was 35.0±54.5 months. In the clinical picture, the most pronounced were febrile fever (83.9%) with an average value of 38.40±1.00 C, cough (58.9%), shortness of breath (28.6%) and chest pain when inhaling (8 ,9%). On radiographs of the chest organs, localized foci of infiltration of the lung tissue were most often found (35.7%), bilateral or multilobar infiltration was somewhat less common (25%), bilateral interstitial infiltration was detected in 12.5% of cases.

Among drug-induced lung lesions, lung damage caused by methotrexate deserves special attention. The incidence of this complication is about 3%. X-ray changes in the lungs in patients treated with methotrexate are represented by diffuse infiltrates and increased pulmonary patterns typical of interstitial pneumonitis. Glucocorticosteroids in moderate doses are effective in treatment.

Comorbid lesions of the endocrine system

The incidence of endocrine system damage in rheumatoid arthritis is 18.8%. The thyroid gland is most often affected (63.4% of all cases of damage to the endocrine system). Thus, the incidence of thyroid disease in rheumatoid arthritis is approximately 12%. These data coincide with the data of other authors: for example, according to the observations of F.V. Valeeva, T.A. Kiseleva (2011), the prevalence of autoimmune thyroiditis among patients with RA ranges from 4 to 28%.

Such a frequent combination of these pathologies can be explained by genetic predisposition: rheumatoid arthritis is associated with HLA DR4 and HLA DR1. Autoimmune thyroiditis is associated with HLA DR3, HLA DR4, HLA DR5.

The main importance in the development of rheumatoid arthritis is given to two closely interrelated processes: activation of CD4+ T lymphocytes of the ThI type and an imbalance between the overproduction of “proinflammatory” cytokines, predominantly of a macrophage nature (TNF-a, IL-1, IL-6, IL-8, etc. .) and anti-inflammatory cytokines (IL-10, soluble IL-1 antagonist, soluble TNF-a receptors, IL-4) with a predominance of production of the former over the latter. Th1 type of immune response is also characteristic of autoimmune diseases of the thyroid gland. In autoimmune diseases of the thyroid gland glands, an imbalance in the production of pro-inflammatory and anti-inflammatory cytokines is also formed, which contributes to the immunopathogenesis of thyropathies and correlates with the severity of the autoimmune process.

In addition, inverse correlations have been established between the levels of T3, T4 and the state of the immune system.

When combined with autoimmune thyroiditis, the course of rheumatoid arthritis has a peculiarity. Thus, among patients with thyroiditis, a more benign course of joint damage is observed (fewer number of swollen and painful joints, lower incidence of ankylosis). However, at the same time, with the development of hypothyroidism, more severe complications were observed (renal amyloidosis and aseptic necrosis).

Antithyroid antibodies play an important role in the diagnosis of thyroid disease. The incidence of antibodies to T3 and T4 was 1–7% in autoimmune thyroid diseases. According to the data presented in the study by O.V. Paramonova, O.A. Rusanova, I.P. Gontar, an increase in antibodies to T3 and T4 was detected in patients with rheumatoid arthritis in combination with autoimmune thyroiditis.

A genetic predisposition is also assumed to be the basis of thyroid lesions in systemic lupus erythematosus. Thus, systemic lupus erythematosus is associated with antigens DR2, DR3, DR4, Dqwl and Dqw2. At the same time, evidence has been obtained that carriage of HLA DR3, DR4 and DR5 is also noted in autoimmune thyroid pathology.

The functional state of the thyroid gland in systemic lupus erythematosus is different: a decrease in gland function is observed, on average, in 4–23% of patients, and an increase in up to 11%.

There was a connection between the frequency and severity of autoimmune thyroiditis and the activity of systemic lupus erythematosus: most often, autoimmune thyroiditis occurred in patients with the 2nd and 3rd degrees of process activity, and, with an increase in the degree of disease activity, there was a decrease in the level of T3 and T4, and an increase in the level of antibodies to thyroglobulin (2 times compared with the 2nd degree and 3 times with the third degree compared with the first). The level of antibodies to thyroid peroxidase was higher in the third degree of activity than in the first or second.

Thus, summing up all of the above, we can draw the following conclusion: damage to the thyroid gland in rheumatic diseases is a fairly common phenomenon. Therefore, in our opinion, it can be recommended to determine the level of thyroid-stimulating hormone in patients with rheumatic diseases without previously identified thyroid lesions at least 1 year and to determine the level of antibodies to thyroid peroxidase or T4 in cases of newly diagnosed autoimmune disease.

Comorbid kidney damage

With systemic connective tissue diseases, kidney pathology often occurs. With rheumatoid arthritis, the incidence of kidney damage is, according to various authors, from 57% to 84.7%, with systemic lupus erythematosus - from 35 to 90%, while in 3-10% of cases the onset of the disease begins with kidney damage.

In rheumatoid arthritis, kidney damage is caused by various factors: immunoinflammatory mechanisms (underlying the pathogenesis of RA and atherosclerosis), AA amyloidosis, toxic effects of drugs (gold drugs, D-penicillamine, cyclosporine A and methotrexate, non-steroidal anti-inflammatory and analgesic drugs). Rheumatoid arthritis occupies a leading place among the causes of secondary amyloidosis. The frequency of occurrence of different glomerular filtration rates in patients with rheumatoid arthritis of different ages is presented in Table 6.

Markers of renal damage can be a decrease in glomerular filtration rate, albuminuria, proteinuria, increased levels of alpha-1-microglobulin (a marker of tubular damage), GGTP (brush border enzyme of the renal tubular epithelium), LDH (cytoplasmic enzyme of the tubular epithelium). At the same time, a correlation was revealed between the markers and the duration: with a duration of the disease from 1 to 5 years, an increase in alpha-1-microglobulin is observed, with a duration of the disease from 5 to 10 years, an increase in alpha-1-microglobulin occurs, and the excretion of GGTP increases.

The mechanisms of kidney damage in vasculitis are different. Thus, ischemic kidney damage is characteristic of Takayasu’s arteritis and polyarteritis nodosa. Glomerulonephritis is characteristic of Wegener's granulomatosis, Churg-Strauss syndrome, Henoch-Schönlein purpura, microscopic polyangiitis (for this pathology, the incidence of kidney damage reaches 90%). For kidney damage due to systemic vasculitis, glucocorticoids are used; for rapidly progressing kidney damage, the use of cyclophosphamide is recommended. In the presence of renal artery stenosis, the issue of performing revascularization operations should be decided.

Comorbid hematological pathology in rheumatic diseases

In rheumatic diseases, hematological disorders (leukopenia, thrombocytosis, anemia, etc.) often occur.

The possibility of development of oncohematological pathology in such patients, which significantly aggravates the prognosis, requires special attention. One possibility is multiple myeloma. Multiple myeloma (MM), along with Waldenström's macroglobulinemia, a heavy chain disease, belongs to the group of paraproteinemic hemoblastoses, which are characterized by monoclonal proliferation of B-lymphoid cells secreting immunoglobulins. A distinctive feature of these diseases is the production of monoclonal immunoglobulin (M-gradient, M-protein, paraprotein), which is determined in blood serum and/or urine.

Risk factors for the development of multiple myeloma include chronic activation of the immune system, high B-lymphocyte activity, therapy with cytotoxic agents and monoclonal antibodies to tumor necrosis factor-α can increase the risk of tumor proliferation.

The difficulty of diagnosis is due to the fact that the same symptoms can occur in both multiple myeloma and rheumatic diseases. With multiple myeloma, joint damage, recurrent purpura (differential diagnosis is necessary, first of all, with hemorrhagic vasculitis), ulcerative necrotic damage to the ENT organs (differential diagnosis with Wegener's granulomatosis), increased uric acid levels (differential diagnosis with gout) and, finally, intoxication syndrome, which occurs in various diseases.

At the Republican Clinical Hospital in Cheboksary, the medical records of 15 patients who had multiple myeloma as a comorbid pathology were studied. When analyzing the results, it should be noted that women predominated in the study (13 out of 15); the most common complaints were ossalgia, arthralgia, and general weakness; among laboratory changes, the most common were anemia, increased ESR, and hyperproteinemia.

In differential diagnosis, it is necessary to pay attention to the level of ESR, the level of proteinuria and the level of total protein, the content of normal (polyclonal) immunoglobulins, the presence of Bence-Jones protein in the urine, and bone radiography data. To confirm the diagnosis of multiple myeloma, a sternal puncture is necessary.

In rheumatic diseases, one of the most common oncohematological pathologies is non-Hodgkin's lymphoma. The relative risk of developing non-Hodgkin lymphoma in patients with rheumatic diseases is 2–7 times higher than in the general population. In rheumatoid arthritis, the risk of occurrence is 26 times higher than in the general population. Non-Hodgkin's lymphomas, which are a heterogeneous group of tumors of lymphoid tissue, are most often (>90%) of B-cell origin. Risk factors for their development, as well as with multiple myeloma, are chronic activation of the immune system and high B-lymphocyte activity. One of the possible etiological factors is the Epstein–Barr virus, parvovirus B19.

BAFF plays a significant role in the survival and maturation of B cells, an increase in which is noted in Sjogren's disease, systemic lupus erythematosus, and rheumatoid arthritis.

In rheumatic diseases, the development of myelodysplastic syndrome (which can transform into acute leukemia) is possible.

Classification (FAB, 1982):

1. Refractory anemia: blast content in peripheral blood< 1 %, в костном мозге < 5 %.

2. Refractory anemia with an excess of ring-shaped sideroblasts: the content of blasts is similar to the first option, but in at least 15% of erythrokaryocytes a circular arrangement of iron-containing granules is determined.

3. Refractory anemia with increased blast content: blast content in peripheral blood< 5 %, в костном мозге 5–20%.

4. Refractory anemia with an increased number of blasts in the stage of transformation into acute leukemia: the number of blasts in the peripheral blood > 5%, in the bone marrow 20–30%.

5. Chronic myelomonocytic leukemia: blasts in the peripheral blood< 5%, в костном мозге 5–20%; содержание моноцитов в периферической крови 10⁹/л.

Thus, with long-term thrombocytopenia, anemia, monocytosis, morphological changes in erythrocytes (multinuclearity, basophilic punctuation of the cytoplasm, etc.), neutrophils (pseudo-Pelger anomaly), a sternal puncture with the study of a myelogram and determination of the content of sideroblasts, as well as trephine biopsy with subsequent histological examination is indicated bone marrow.

Conclusion.

The problem of comorbid conditions in rheumatic diseases is interdisciplinary.

In rheumatic diseases, a wide range of comorbid conditions is possible, which makes their further study and further development of recommendations for the tactics of examination and treatment of these patients extremely relevant.

It is necessary to differentiate comorbid diseases from systemic manifestations. An individual approach to each patient is necessary.

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