Systemic scleroderma: symptoms and treatment.

Scleroderma is a rare systemic disease characterized by thickening, hardening of the skin and connective tissue.

There are 2 types of scleroderma: localized and systemic scleroderma .

Localized scleroderma is an inflammatory sclerotic lesion of the skin without involving internal organs in the pathological process.

Systemic scleroderma affects, in addition to the skin, also internal organs - the heart, alimentary tract, lungs, kidneys.

Scleroderma does not pose a danger to other people; the disease is not contagious. But it significantly reduces the quality of life of the patient himself and poses a direct threat to his life.

All patients with scleroderma should be observed by a rheumatologist. If time is missed, systemic scleroderma can cause numerous complications.

Consultation with a rheumatologist

2 Consultation with a rheumatologist

3 Consultation with a rheumatologist

Lack of blood circulation in scleroderma leads to tissue necrosis in the extremities, gangrene and possible amputation of fingers or toes. Damage to kidney tissue is dangerous due to renal scleroderma crisis. Inflammation of the gastrointestinal tract, cardiac complications and pulmonary hypertension are also possible. Only timely, adequate treatment will help maintain health, and in some cases save the life of a patient with systemic scleroderma.

Causes of systemic scleroderma

The disease systemic scleroderma begins as a result of the appearance of excess collagen in the skin and other tissues of the human body. Collagen is a type of protein that forms the basis of skin and connective tissue.

The reasons for this phenomenon have not been fully established, but many scientists believe that our immune system is “to blame” for this. As a result of an unknown malfunction, it triggers a mechanism that stimulates excessive production of collagen (connective tissue protein).

Risk factors for the development of systemic scleroderma may include:

gender of the person (women get this pathology 4 times more often than men);
race (people with dark skin suffer from this disease much more often than white-skinned people);
external factors that provoke the onset of the disease (hypothermia, exposure to chemicals, certain types of medications, prolonged stress, etc.).

Signs related to internal organs

Since the disease involves connective tissue and greatly affects internal organs, patients can have a full range of problems with the gastrointestinal tract, heart, kidneys and other systems. They are manifested by any signs of the corresponding diseases. Very often (in 70% of cases) the lungs are affected - it is lung diseases that often cause the death of the patient. In this case, scleroderma can cause pneumonia, abscesses and even lung cancer, which is 3-5 times more common in people with this disease than in other representatives of the same age groups.

It is important to understand that there is no clear list of symptoms in this case - otherwise it would be huge. The disease is dangerous because it affects almost the entire body and can manifest itself in any way.

Symptoms of scleroderma

Symptoms of scleroderma can be very diverse, depending on which organs are affected. Due to the fact that some symptoms of systemic scleroderma are similar to those of other diseases, diagnosis can be difficult.

We list the most common manifestations of this pathology:

Raynaud's syndrome, characterized by narrowing of the blood vessels in the arms and legs, the limbs become pale, cold and numb;
Arthritis and limited finger mobility may cause misdiagnosis of rheumatoid arthritis;
gastroesophageal reflux disease, accompanied by sour belching, which damages the walls of the esophagus, hence problems with the absorption of nutrients, anemia is possible;
changes in some areas of the skin include the appearance of swelling in the area of the fingers and hands, thickening of certain areas of the skin (when pressure is applied to the skin, no depressions remain), tightening of the skin on the hands, face and around the lips;
lung damage, in which the first symptom is shortness of breath on exertion. Then comes a prolonged cough, pain in the side;
kidney damage, which can lead to renal ischemia, glomerular necrosis, renal failure and, in the absence of adequate treatment, death.

Forms and symptoms of localized scleroderma:

There are 2 forms of localized scleroderma:

The plaque form appears as oval-shaped thickenings on the skin, with a red border around the edges and a white circle in the middle. Sometimes this disease can disappear within 3-5 years, but pigmented areas remain on the skin.
Linear scleroderma most often occurs in children. It is characterized by the appearance of thickenings in the form of “ribbons” on the skin of the face, arms and legs. May appear asymmetrically, affecting only one part of the body.

One of the first signs of localized scleroderma is a sharp whitening of the fingers (a symptom of Raynaud's disease).

Symptoms of systemic scleroderma

Systemic scleroderma leads to inflammation of the skin, blood vessels, and affects the joints of the arms and legs, as well as internal organs. The disease systemic scleroderma can have many different types, depending on the organs affected by the pathological process.

With systemic scleroderma, the skin quickly becomes inflamed, and then, in some cases, the skin changes may go away on their own.

Classification of the disease according to several criteria

If we talk about the clinical form, the classification of scleroderma includes the following options:

diffuse. It develops quickly and within six months reveals itself with a host of symptoms. Affects the face, head, torso, limbs;
limited. Mainly affects the face, hands and feet, and develops much more slowly;
cross. Combined with other autoimmune diseases, such as lupus erythematosus or rheumatoid arthritis;
visceral (without scleroderma). That is, the skin with this type of disease does not thicken, but Raynaud's syndrome manifests itself (whitening, numbness, blue discoloration of the fingers or toes). The main blow falls on the internal organs - the gastrointestinal tract, lungs, kidneys;
induced. May be associated with vascular lesions, usually caused by environmental factors, such as exposure to cold or chemicals;
juvenile This type is typical for early ages, up to 16 years. As a rule, it affects internal organs less, but can cause abnormalities in the development of limbs and other serious problems.

Scleroderma can also be rapidly progressive (acute), moderately progressive (subacute) and slowly progressive (chronic).

Diagnosis of systemic scleroderma

To confirm the diagnosis, a rheumatologist may prescribe the following examinations:

general blood analysis;
general urine analysis;
blood chemistry;
rheumatic tests (may show increased amounts of certain antibodies);
skeletal muscle biopsy;
electromyography.

In addition, other tests may be required to determine the state of the heart, lungs, and gastrointestinal tract.

1 General blood test

2 Biochemical blood test

3 Diagnosis of systemic scleroderma in MedicCity

Treatment of systemic scleroderma

While localized scleroderma can go away on its own, systemic scleroderma requires significant effort to treat. There is currently no radical treatment method, but rheumatologists have drugs in their arsenal that allow them to control the manifestations of the disease and prevent its complications.

Drug treatment of systemic scleroderma includes the following areas:

vascular therapy (drugs with vasodilating properties help minimize the manifestations of Raynaud's disease);
immunosuppressive therapy (prescription of immunosuppressive drugs that suppress autoimmunity, which provokes this disease);
antifibrotic therapy (prescribed for the diffuse form of scleroderma to disrupt collagen synthesis);
anti-inflammatory therapy (to eliminate damage to internal organs involved in the pathological process).

Non-drug treatment of scleroderma is represented by the following methods:

physiotherapeutic procedures;
cosmetic procedures aimed at improving the appearance of the skin.

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Professional rheumatologists will help you find the true cause of the disease and prescribe effective treatment.

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Scleroderma is a chronic inflammatory disease of connective tissue with a long-term and progressive course, manifested by changes in the skin and internal organs. The etiology of this disease is not fully understood. Immune and genetic factors, damage to small vessels, increased collagen synthesis by fibroblasts, as well as the use of certain medications, and the presence of concomitant somatic pathologies, such as cancer, play an important role in the development of dermatosis. Scleroderma is statistically more common in women aged 20-50 years.

We examined 89 patients suffering from scleroderma and hospitalized for treatment in the hospital branch of the Korolenko Clinic in 2012-2013. We paid attention to the presence of concomitant diseases in the patients we observed and compared them with those described in the specialized literature.

M. González-López et al. [1] traced the relationship between systemic scleroderma (SSc) and primary biliary cirrhosis. Only 6 such cases were described in the specialized literature and all of them were observed in women. The authors described the case of a 62-year-old man with multiple inflammatory macules on the trunk and extremities that appeared three years earlier. Clinical and laboratory data, as well as histological studies, were consistent with the diagnosis of S.S. The coexistence in men of two diseases that predominantly affect women supports the hypothesis that there is a pathogenetic connection between these two conditions. The authors draw our attention to the fact that primary biliary cirrhosis should be sought in all patients with S.S. Among our patients there were no patients suffering from primary biliary cirrhosis.

J. Chappell et al. [2] described the case of a 60-year-old white woman with cutaneous manifestations of Rosai-Dorfman disease and coexisting S. According to the authors, this is the first report of the coexistence of these two pathologies in the same patient.

R. Ludwig et al. [3] in their article consider chronic venous insufficiency (CVI) as a potential trigger factor in the development of limited scleroderma (LS). The authors, citing the authority of other researchers (Seifarth et al.) and their own experience, describe cases of the development of OS in the field of CVI. Treatment of CVI in such patients led to a significant improvement in the clinical picture of C in the area of the affected veins, but did not affect the rash in other places. Chronic venous insufficiency was observed in one of our patients. In addition, varicose veins of the lower extremities were found in 11 patients we examined, which leads to the development of CVI.

In the specialized literature, a connection is often noted between autoimmune diseases, such as scleroderma, discoid or systemic lupus erythematosus, vitiligo, and diabetes mellitus (DM). M. Yamamoto et al. [4] described the case of a 49-year-old Japanese woman with discoid lupus erythematosus (DLE) of the face. She also had Raynaud's phenomenon, finger swelling, high titers of antinuclear antibodies, and biopsy results showed limited type SS. Combination S.S. and DLE are quite rare, although some similar cases have already been described in Japan. The patient also had hepatitis C. Among our patients there were no patients suffering from DLE and hepatitis C.

C. Bonifati et al. [5] described the case of a 21-year-old man with concurrent LS on the left upper limb and homolateral segmental vitiligo on the trunk. Since these diseases appeared at the same time, and the process involved one side of the body, the authors concluded that perhaps the connection between the two diseases was not accidental.

H. Zeglaoui et al. [6] described a case of coexistence of four autoimmune diseases in a 15-year-old girl: diabetes, SS, celiac disease and systemic lupus erythematosus. The authors in their article discussed the etiopathogenesis and connection between these diseases.

There are a large number of studies describing the development of scleroderma against the background of existing cancer. Among our patients, only one had a history of thyroid cancer.

A. Scope et al. [7] examined the cases of all patients with scleroderma and breast cancer who were hospitalized during 1980–2002. The data obtained were compared with literature data on patients with breast cancer and scleroderma. The clinical data of 65 women with breast malignancy and scleroderma were summarized, of whom 8 patients were hospitalized, and the clinical data of 57 patients were described in the literature. In 29 (44%) women, scleroderma developed before or at the same time as breast cancer diagnosis. Although this group of patients had a high incidence of SS, a high incidence of OS occurred in the group where the development of the skin process followed the diagnosis of breast cancer. The study highlights the link between scleroderma and breast cancer.

K. Kikuchi et al. [8] observed 71 patients with sclerotic skin changes from 1994 to 2002; 66 (93%) of them were diagnosed with SS, and in 5 (7%) the authors diagnosed pseudoscleroderma associated with various malignant neoplasms. The duration of the disease in these 5 patients was shorter than in patients with S.S. The presence of antinuclear antibodies, Raynaud's phenomenon, or esophageal problems was significantly less pronounced in patients with pseudoscleroderma than in patients with SS. Serum levels of basal fibroblast growth factor (bFGF) were significantly elevated in 5 patients with pseudoscleroderma compared with controls.

Cases of simultaneous coexistence of OS and squamous cell carcinoma have been described several times in the specialized literature. M. Greco et al. [9] described multiple foci of squamous cell carcinoma on the skin of the leg that appeared in a patient with OS.

G. Androutsopoulos et al. [10] described the case of a 43-year-old, nulliparous, perimenopausal Greek woman with scleroderma who presented with abdominal pain and vaginal bleeding. The woman underwent a hysterectomy with bilateral removal of the appendages, complete excision of the omentum, removal of the appendix, and revision of the pelvic lymph nodes. Histopathology showed synchronous primary cancers of the lining of the uterus and the left ovary. The patient underwent postoperative chemotherapy and remained in good disease-free condition 25 months after surgery. Synchronous primary cancers of the lining of the uterus and ovary are relatively rare in the general population. Only a few cases of cancer of the female genital tract in patients suffering from scleroderma have been reported in the literature.

S. Nunez et al. [11] reported a patient with scleroderma, renal cell carcinoma (RCC) and membranous nephropathy. Certain clinical and laboratory findings suggested that RCC caused or facilitated the development of the other two conditions. Carcinoma of the left renal apex was removed by nephrectomy. Membranous nephropathy was found in the renal parenchyma adjacent to the removed tumor. 3.5 years after surgery, the clinical manifestations of scleroderma stopped, although the number of medications was greatly reduced. This case provides an example of the development of three rare diseases (scleroderma, RCC and membranous nephropathy) in one person, the long-term improvement in the manifestations of scleroderma and membranous nephropathy that occurred after removal of the RCC, contrasted with the rapid deterioration of these conditions before surgery. The patient had autoantibodies in the serum that are rare in patients with scleroderma, which is likely associated with malignancy and suggests a pathogenetic relationship between the three conditions.

A. Dancey et al. [12] traced the connection between radio radiation and the development of scleroderma. Cases of scleroderma caused by radio radiation were first described in 1900. Cases of scleroderma caused by radiation occur with a frequency of 2:1000. The spread of the process beyond the irradiated area is observed in approximately ¼ of cases. The authors described 2 cases of scleroderma on the skin of the breast. In the first patient, the development of scleroderma was not associated with breast pathology. The patient underwent Wise surgery with removal of the scleroderma focus within healthy skin. In the second patient, scleroderma developed after a course of radiotherapy for breast cancer. The patient refused surgical intervention. The article emphasizes that scleroderma is a recognized complication of radiotherapy that must be distinguished from sclerotic recurrence of the primary tumor.

S. Dubner et al. [13] described the case of a 52-year-old woman who underwent removal of a breast tumor followed by radiotherapy. 2 years after the operation, changes appeared on the skin in the area of irradiation in the form of hyperpigmentation, retraction and thickening of the skin. The clinical and histological picture made it possible to diagnose OS after irradiation. The authors emphasized that it is important to be aware of these rare complications after radiotherapy.

K. Nakamura et al. [14] described the case of a 65-year-old woman with chronic graft-versus-host disease, manifested by sclerotic changes on the skin of the upper extremities and trunk after transplantation of autologous peripheral blood stem cells. The patient suffered from breast cancer. After surgery and chemotherapy, she developed pancytopenia for which autologous peripheral blood stem cell transplantation was performed. 4 years after transplantation, the patient developed severe sclerosis on the skin of the upper extremities and trunk. Skin biopsy showed thinning of the epidermis and proliferation of collagen bundles in the dermis. There was a lack of antinuclear DNA titers in the serum. The patient was diagnosed with chronic graft-versus-host disease. Despite treatment with oral prednisolone,

skin sclerotic changes continued to develop and breast cancer recurred.

M. Juarez et al. [15] described a case of a patient with secondary scleroderma as a manifestation of paraneoplastic syndrome in hairy cell leukemia. Also, one of our patients had a history of hairy cell leukemia.

Autoimmune diseases can manifest as paraneoplastic syndrome in cancer, most often as dermatomyositis/polymyositis. In this article G. Orphanos et al. [16] described the case of a 56-year-old man with rectal cancer and S.S. The development of these two diseases was so connected that scleroderma was considered a paraneoplastic syndrome against the background of cancer, and not a concomitant disease.

Among the forms of the disease that we observed in patients at the City Clinical Hospital No. 14 named after. V.G. Korolenko, focal and linear scleroderma, lichen sclerosus, Pasini-Pierini atrophoderma and Tibierge-Weissenbach syndrome were noted.

The clinical picture of OS is represented by single or multiple spotted elements of pink-lilac color with a clear border of a round or oval shape. Over time, the color of the element changes from pink-lilac to yellowish-white (“ivory”), the lesion becomes denser, and later atrophy develops in it. Along the periphery of the lesion there is a pink-lilac rim, which indicates the activity of the process. At the site of atrophy, the skin pattern is smoothed out, sensitivity weakens, and there is no sebum or sweating. The lesion begins to shine and gradually the color of the lesion changes to brown. The skin in the lesion becomes thinner. Rashes develop on any part of the skin. Among our patients, OS was observed in 74 patients.

Linear scleroderma most often develops in young women or children. The rashes are most often localized on the scalp or extremities. This form of dermatosis got its name from the shape of the eruptive element, which has a linear shape and resembles a scar after a saber strike. In the patients we observed, foci of linear scleroderma were present on the skin in 5 patients.

The clinical picture of lichen sclerosus is represented by small spotted whitish rash elements, most often localized on the skin of the neck and chest, as well as in the genital area. Along the periphery of the spots there may be a pink-lilac corolla. Over time, the central part of the spots becomes retracted and atrophy develops. The dilated openings of hair follicles and sweat glands can be filled with horny plugs. Lichen sclerosus is also characterized by the presence of petechiae and telangiectasia. On the genitals, lichen sclerosus is represented by foci of dryness, thinning and atrophy of the skin, up to a narrowing of the entrance to the vagina. Patients are sometimes bothered by itching. The disease most often develops in women aged 50-60 years, which is likely due to hormonal imbalances and the presence of a large number of concomitant pathologies. Among the patients we observed, 8 had lichen sclerosus rashes.

Pasini-Pierini atrophoderma is characterized by several pinkish-bluish spots of a round or oval shape. This disease most often affects young women. Over time, the thickening characteristic of scleroderma does not develop. The lesion acquires a brownish-brown tint and atrophy is noted. The corolla along the periphery of the lesion, accompanying scleroderma, is also absent. Due to the absence of these two symptoms, which always accompany scleroderma, according to some authors, this disease can serve as a manifestation of the late stage of ixodic tick-borne borreliosis (M.A. Paltsev et al., 2004) [17]. Among our patients there was one patient with this diagnosis. At the same time, there are clinical cases where one patient simultaneously has foci of Pasini-Pierini atrophoderma and OS.

Tibierge-Weissenbach syndrome is rare. It is characterized by a combination of scleroderma and calcification of the skin. Among our patients, only one had Thibierge-Weissenbach syndrome.

Among the 89 patients in the hospital of the Korolenko Clinic branch there were women aged from 23 to 80 years. The age distribution of patients is presented in Fig. 1. In the examined group there were 3 patients aged from 20 to 30 years, 7 patients - from 31 to 40 years, 6 - 41-50 years, 23 - 51-61 years, 27 - from 61 to 70 years, 23 in the age range of 71-80 years.

Rice. 1. Age of patients.

Among the patients, 74 patients had OS, 8 patients suffered from lichen sclerosus, 5 patients were diagnosed with linear scleroderma. One patient suffered from Tibierge-Weissenbach syndrome and one patient was diagnosed with Pasini-Pierini atrophoderma. The distribution of forms of the disease is presented in Fig. 2.

Rice. 2. Forms of the disease.

The duration of the disease ranged from 1 month to 35 years. Three patients were observed for disease duration of up to 1 year. In 63 patients, the duration of the disease varied from 1 year to 5 years, in 13 patients - from 6 to 10 years, 7 patients - from 11 to 20 years, 3 patients - more than 20 years, of which 1 considered herself sick for 26 years, 1 patient - 30 years and 1 - 35 years. The distribution of disease duration is shown in Fig. 3.

Rice. 3. Duration of the disease.

Concomitant pathological processes were observed in 89 (100%) people: diseases of the cardiovascular system were found in 45 (50.6%), of which 45 (50.6%) suffered from arterial hypertension, 32 (35.9%) from ischemic hypertension. heart disease, 6 (6.7%) - heart rhythm disturbances. Gastrointestinal tract (GIT) complaints were received from 31 (34.8%) patients: 2 (2.2%) had cholelithiasis, 15 (16.9%) had cholecystitis, 6 (6.7%) %) - fatty hepatosis, gastric and duodenal ulcers affected one (1.1%) patient each, chronic gastritis was observed in 30 (33.7%) patients, 1 (1.1%) patient suffered from ulcerative colitis. 11 (12.3%) patients suffered from kidney diseases: pyelonephritis - 8 (8.9%) patients, kidney cysts - 5 (5.6%). Thyroid diseases were noted in 31 (34.8%) patients: nodular goiter - in 17 (19.1%), hypothyroidism - in 10 (11.2%), autoimmune thyroiditis - in 8 (8.9%), cancer There was a history of thyroid disease in 1 (1.1%) patient. 17 (19.1%) patients suffered from type 2 diabetes, while 11 (12.3%) women had complications of diabetes, such as diabetic retinopathy in 3 (3.3%), retinal angiopathy in 8 (8, 9%) patients and diabetic polyneuropathy in 2 (2.2%). 10 (11.2%) patients suffered from respiratory tract diseases: chronic bronchitis - 10 (11.2%) patients, bronchial asthma - 1 (1.1%) and chronic tonsillitis - 4 (4.5%). Hairy cell leukemia was noted in the anamnesis in 1 (1.1%) patient. Concomitant diseases observed by us in the examined patients are presented in Fig. 4.

Rice. 4. Concomitant somatic diseases.

Thus, the authors would like to draw attention to the fact that 100% of the patients had concomitant diseases of various organs and systems. This indicates the need for careful examination of patients with scleroderma. In addition, in the examined cohort of patients, 39 (43.8%) patients aged 20 to 60 years are a socially active group. Reports of a frequent association of scleroderma and cancer pathology also deserve great attention. This fact was not confirmed in our study. However, we consider it necessary to conduct research, including in this direction.

There is no conflict of interest.