Lupus panniculitis. Purulent diseases and subcutaneous fatty tissue

Panniculitis (Pn) are diseases of a heterogeneous nature, which are characterized by pathological changes in the subcutaneous fatty tissue (SFA). Often these diseases also affect the musculoskeletal system.

What's the problem with diagnostics?

Mon are diverse in their clinical and morphological manifestations, exists a large number of forms of the disease, while there are currently no criteria that would lead to a common denominator for diagnosis. Patients with PN turn to different specialists precisely because of the polymorphism of clinical symptoms. Such situations lead to an insufficiently rapid diagnosis, and therefore treatment begins untimely.
Attempts at classification

At present, there is no classification that would be uniform for all countries of the world. Some authors offer their vision and organize Pn according to etiology and pathomorphological picture. Thus, septal (SPn) and lobular are now distinguished panniculitis(LPn), that is, an inflammatory process located in the connective tissue septa and in the lobules of adipose tissue, respectively. Both variants of the disease can be combined with symptoms of vasculitis and occur without it.

Erythema nodosum (EN)

UE is typical representative septal panniculitis. The immunoinflammatory process in this pathology is nonspecific. There are many reasons for its appearance:

There are primary and secondary UE. Primary is most often idiopathic. Clinical symptoms that occur with UE are characterized by the state of the immune system, the etiology of the disease, the localization of the pathological focus, as well as its prevalence.

UE can be diagnosed only after a carefully collected medical history, patient complaints, based on the clinic and research data, laboratory and instrumental.

Brief description of clinical example No. 1

The patient is 31 years old and has a history of chronic tonsillitis since the age of 15 and frequent use of antibiotics for it. In 2009, painful nodes were discovered after another exacerbation of tonsillitis. The nodes were located on the left shin. Treatment was carried out with the glucocorticosteroid hormone dexamethasone, after which positive dynamics were observed.

After 3 years, tonsillitis provoked the appearance of 2 more nodes on the legs. After two months of homeopathic therapy, the nodes regressed. At the end of the year, the painful formations on the lower leg recurred again.

Upon admission, the general condition was satisfactory, the physique was normosthenic, and the body temperature was normal. Other indicators of examination and laboratory tests were also unchanged. When palpating the formations on the lower leg, pain is noted. Ultrasound of the node revealed an area of some blurriness with increased echogenicity And high content

vessels. The diagnosis made by doctors sounded like erythema nodosum
Stages 2-3 and chronic tonsillitis. After treatment with benzylpenicillin, non-steroidal anti-inflammatory drugs, the introduction of a protective regimen and local treatment with clobetasol sodium and heparin ointments, the disease regressed after 21 days. There were no exacerbations of the pathology during the year. panniculitis Of the causes of the disease, streptococcal infection is in first place, 9 and the case described above indicates an association of UE (septal

) with streptococcal infection, in particular with sore throat) is sarcoidosis.

Brief review of clinical case No. 2

A 25-year-old patient was admitted to the hospital with complaints of painful nodular formations on the legs and arms, pain in many joints (ankles, wrists), swelling in them, an increase in body temperature to 39C, and increased sweating. She became ill on December 7, 2013, when arthritis of the ankle joint first appeared.

After 2 days, nodes appeared on the legs, which were sharply painful. Within a few days, a large number of the same formations appeared with symptoms of general intoxication (fever, sweating).

After examination by a therapist, a diagnosis of probable reactive arthritis was made. Dexamethasone was used for treatment. The effect was positive. However, relapses continued. According to laboratory data, inflammatory changes were determined in the blood. On CT scan of organs chest

After consultation with a pulmonologist, sarcoidosis of the intrathoracic lymph nodes was diagnosed. Final diagnosis looked like Lefgren's syndrome, sarcoidosis of the chest lymph nodes at stage 1, secondary UE, polyarthritis, febrile syndrome.

The patient was treated with dexamethasone and cyclophosphamide parenterally. Then methylprednisolone was prescribed orally. Cyclophosphamide was also administered weekly, accompanied by a non-steroidal anti-inflammatory drug. The therapy led to positive dynamics of the disease and the patient is currently under medical supervision.

Differential diagnosis of UE

There are many diseases whose clinical picture is similar to the symptoms of UE, so it is necessary to carry out a careful differential diagnosis. If differential diagnosis is carried out incorrectly or at the wrong time, inadequate therapy is prescribed, which leads to prolongation of the disease and the appearance of various complications and a deterioration in a person’s quality of life.

Clinical case example No. 3

A 36-year-old female patient came to the hospital for medical care at the beginning of 2014 due to complaints of tightness in the lower leg, which was painful. The patient believes that the disease first appeared in 2012 after (ARVI). Then it appeared on my shins painful lump. Doctors diagnosed thrombophlebitis. Treatment with vascular drugs was carried out, and physiotherapy was prescribed. The patient completed treatment with positive dynamics. In April 2013, the painful lump appeared again. Laboratory tests were carried out and did not reveal inflammatory changes. Ultrasound of the veins revealed insufficiency of the perforating veins of the leg. The patient was sent for consultation to NIIR named after. V.A. Nasonova”, where during the examination a lump was discovered on the lower leg. Laboratory and instrumental studies within normal limits. Ultrasound of internal organs shows some diffuse changes in the pancreas and liver. Ultrasound of the node shows microvascularization, lumpiness of the structure and thickening of the pancreas.
After all examinations and consultations, a diagnosis of lobular panniculitis, chronic course, lipodermatosclerosis. Varicose veins veins of the lower extremities. Chronic venous insufficiency class IV.

Treated with hydroxychloroquine due to weak activity diseases. A month later, the dynamics of the disease are positive.

Discussion of case features

We have presented to your attention 3 different cases of differential diagnosis, which are very common at the moment.

In the first patient, after a streptococcal infection, the disease regressed on the background of antibiotics and anti-inflammatory drugs. Moreover, let us note the color dynamics of formations on the skin: a pale red color at the beginning to a yellow-green color at the end of the disease, the so-called symptom of bruise bloom.

For UE, this dynamics is very characteristic and even in the later stages of the disease it can be determined. The nodules themselves disappear without a trace after 3-5 weeks. No skin atrophy or scars are observed.
Simultaneously with skin manifestations, it also manifests joint syndrome. Pain and swelling in the joint area occur in half of patients with UE. The most common lesion is the glenostop joints. Regression of arthritis is observed within six months. Such patients do not develop heart damage, as with rheumatism, even though joint pain appears after the primary streptococcal infection.

If patients with UE have valvular heart pathology, it does not worsen. In this regard, we can say that UE is not a reflection of the activity of the rheumatic process.

UE and sarcoidosis

Against the background of sarcoidosis, UE has features of its course and manifestations:

swelling of the legs, which often precedes UE;
severe joint pain;
There are quite a lot of skin compaction elements and they are extremely common, and each element is capable of merging with another similar unit;
localization of nodes mainly in the area of the legs;
the dimensions of the elements are large, more than 2 cm in diameter;
in laboratory tests there may be an increase in the titer of antibodies to antistreptolysin-O and to yersinia;
damage to the respiratory tract with symptoms such as shortness of breath, chest pain, cough.

UE (septal panniculitis), hilar lymphadenopathy, fever, and joint involvement are suggestive of Löfgren's syndrome. Despite this, enlarged lymph nodes can also occur with

Panniculitis is an inflammatory lesion of the subcutaneous fatty tissue, which can ultimately lead to its complete destruction. Sometimes this pathology is also called fatty granuloma. It was first described in 1925 by Weber. According to statistics, panniculitis most often affects women aged 20 to 50 years.

What is panniculitis?

Panniculitis is characterized by the absence specific symptoms, so it is quite often confused with other skin diseases. There is also no consensus among doctors about the reasons why this disease may occur.

According to statistics, in approximately 40-50% of cases, inflammation of fatty tissue occurs against the background of relative health. It can be provoked by pathogenic or opportunistic bacteria, viruses and even fungi that penetrate the adipose tissue through damaged skin.

The development of inflammation of adipose tissue is based on disorders of one of the metabolic mechanisms in adipose tissue, namely lipid peroxidation, which can occur for various reasons.

Types of disease

Depending on whether the inflammation of the subcutaneous tissue appeared independently or occurred against the background of some other pathology, panniculitis can be primary (idiopathic) or secondary. The primary form of the disease is also called Weber-Christian panniculitis.

There is another classification of pathology. Depending on the nature of the changes that occur on the skin, it can be:

Nodular, in which single nodes, isolated from each other, ranging in size from several millimeters to a centimeter, appear under the skin. The skin over them becomes burgundy and may swell.
Plaque, manifested by the formation of many single compactions, which can grow together into fairly large conglomerates. In severe cases, they can compress blood vessels and nerve endings, cause the development of edema, poor circulation and loss of sensitivity.
Infiltrative, in which panniculitis looks like an abscess or phlegmon. The only difference between them is that yellowish liquid accumulates inside the nodes, not pus. After opening the node, a poorly healing ulceration remains in its place.
Visceral, in which manifestations on the skin are accompanied by damage to internal organs. This happens due to the fact that the pathology affects the retroperitoneal tissue. Typically, this form affects the liver, pancreas and kidneys.

Regardless of the type, panniculitis can occur in acute, most severe, or subacute form. Sometimes able to accept chronic nature a course in which exacerbations are usually mildest and are separated by long periods of remission.

Causes

Primary inflammation of the subcutaneous adipose tissue can occur due to the penetration of infection into the subcutaneous adipose tissue. Its development can be triggered by injuries, even minor ones, burns or frostbite, as well as insect or animal bites. As for the secondary form of pathology, depending on the cause, panniculitis can be:

Immunological, that is, develop due to disorders in immune system, for example, with systemic vasculitis or erythema nodosum.
Lupus, which occurs against the background of systemic lupus erythematosus.
Enzymatic, occurring against the background of developed pancreatitis due to high activity pancreatic enzymes.
Proliferative cellular, which is provoked by pathologies such as leukemia or lymphoma.
Artificial or medicinal, which develops due to the use of certain medicines. An example of such a pathology is steroid panniculitis, which often develops in children after a course of corticosteroids.
Crystalline, occurring against the background of gout and renal failure which lead to deposition in subcutaneous tissue calcifications or urates.
Genetic, developing due to a hereditary disease in which there is a deficiency of the enzyme 1-antitrypsin. Most often, it is this reason that causes the development of the visceral form of the disease.

With the exception of drug-induced panniculitis, which in most cases goes away on its own over time, all other forms of the disease require mandatory treatment. Only a doctor should prescribe it.

Symptoms

The main symptom of the disease is the growth of plaques under the skin or the appearance of single nodes. They are located mainly on the legs or arms, less often in the abdomen, chest or face. In addition, symptoms of the disease include:

Redness in the affected area, soreness and local increase temperature.
Reds small dots, rash or blisters on the skin.
Signs of general intoxication of the body, such as weakness and pain in muscles and joints, headache and fever, especially when panniculitis is caused by viruses.

In addition to general symptoms, with the visceral form of pathology, signs of damage to various organs will also appear. If the liver suffers, then symptoms of hepatitis will appear; if the kidneys are affected, nephritis will appear; and in the case of the pancreas, pancreatitis will appear. In addition, with the visceral form, characteristic nodes will form on the omentum and in the retroperitoneal space.

If you notice warning signs on your skin, consult a doctor as soon as possible. A dermatologist, dermatovenerologist, infectious disease specialist, surgeon or therapist can help you in this case.

Treatment

Unfortunately, panniculitis is one of those pathologies that require long-term and complex treatment, especially if the patient did not consult a doctor in time and the diagnosis was made late. In acute form, the disease can last 2-3 weeks, in subacute or chronic form - up to several years. However, regardless of the form of the pathology, treatment will always be comprehensive.

In each case, the doctor selects an individual treatment regimen depending on the patient’s characteristics and the presence or absence of concomitant diseases.

In addition, for nodular and plaque forms of panniculitis, the regimen may include cytostatic drugs, such as Methotrexate or Azathioprine.

The most difficult to treat is the infiltrative form of panniculitis. In severe cases they don’t even help large doses glucocorticosteroids and antibiotics. Therefore, to treat this pathology, in some situations, doctors prescribe tumor necrosis factor (TNF) drugs.

In addition to the main drugs, the treatment regimen may also include auxiliary agents, for example, hepatoprotectors or antioxidants. Physiotherapy may also be prescribed: phonophoresis, magnetic therapy or ultrasound.

Possible complications and prevention

Since the exact mechanism of development of the disease is still unknown, there is no specific prevention of panniculitis as such. The exception is the secondary form, in which doctors advise not to allow an exacerbation of the primary pathology that provokes the development of panniculitis.

As for the prognosis and complications, first of all it will depend on the specific form of the disease and when the diagnosis was made and treatment began. Panniculitis, treatment of which is started in the early stages, goes away much faster and is less likely to cause complications.

The most unfavorable and severe course is the acute form of panniculitis, which can often be complicated by sepsis. Subacute and chronic forms, as a rule, in most cases resolve over time without complications.

Panniculitis or fatty granuloma is a disease that leads to necrotic changes in the subcutaneous fatty tissue. The disease is prone to relapse.

As a result inflammatory process for panniculitis fat cells are destroyed and replaced by connective tissue with the formation of infiltrates of plaques or nodes.

The most dangerous is the visceral form of panniculitis, which affects adipose tissue internal organs - kidneys, pancreas, liver, etc.

Reasons for the development of the disease

These diseases most often affect women of reproductive age.

In approximately half of patients, fatty granuloma develops spontaneously, that is, against a background of relative health. This form It is more common in women of reproductive age and is called idiopathic.

In the remaining 50% of patients with panniculitis, inflammation of adipose tissue develops as one of the symptoms of a systemic disease - sarcoidosis, lupus erythematosus, etc.

The cause of panniculitis may be immune disorders, exposure to cold, reaction to taking certain medications.

Doctors believe that the basis for the development of fat granuloma is pathological change metabolic processes in adipose tissues. However, despite many years of research and study of panniculitis, to date it has not been possible to obtain a clear understanding of the mechanism of development of the inflammatory process.

Classification of forms of the disease

In dermatology, primary and secondary forms of fatty granuloma are distinguished.

In the first case, panniculitis develops without the influence of any factors, that is, for unknown reasons. This form is called Weber-Christian syndrome and most often occurs in women under 40 years of age who have excess weight.

Secondary panniculitis occurs due to various reasons, which made it possible to develop a certain system for classifying forms of the disease.

Highlight following forms panniculitis.

Immunological panniculitis. The disease develops against the background systemic vasculitis. Sometimes this variant of fatty granuloma is detected in children as a form of erythema nodosum.
Fermentative panniculitis. The development of inflammation is associated with the action of enzymes produced by the pancreas. As a rule, it manifests itself against the background of pancreatitis.
Proliferative cell fatty granuloma develops in patients with lymphoma, histiocytosis, leukemia, etc.
Lupus panniculitis is one of the manifestations of lupus erythematosus, which occurs in an acute form.
Cold panniculitis develops as a local reaction to hypothermia. It manifests itself by the appearance of dense nodes, which spontaneously disappear after a few weeks.
Crystalline panniculitis is a consequence of gout or kidney failure. Develops due to the deposition of urates and calcifications in the subcutaneous tissue.
Artificial fat granuloma develops at the injection site after the administration of various drugs.
The steroid form of panniculitis often develops in children as a reaction to treatment with steroid drugs. No special treatment is required; the inflammation goes away on its own after stopping the medication.
Hereditary form Panniculitis develops due to a deficiency of a certain substance - A1-antipripsin.

In addition, there is a classification of forms of panniculitis depending on the type of lesions on the skin. There are plaque, nodular and infiltrative forms of fatty granuloma.

Clinical picture

Panniculitis can occur in acute, recurrent or subacute form.

The acute form of fatty granuloma is characterized by a sharp development, deterioration of the patient’s general condition, and disturbances in the functioning of the kidneys and liver are often observed. Despite treatment, relapses follow one after another, each time the patient’s condition worsens. The prognosis for acute panniculitis is extremely unfavorable.
Fatty granuloma, occurring in a subacute form, is characterized by more mild symptoms. Timely treatment, as a rule, has good effect.
The most favorable form of the disease is considered chronic or recurrent panniculitis. In this case, exacerbations are not too severe, and long remissions are observed between attacks.

The symptomatic picture of panniculitis depends on the form.

Primary (idiopathic) form

The main symptoms of spontaneous (primary) fat granuloma are the appearance of nodes located in the subcutaneous fat. Nodes can be located at different depths. In most cases, nodes appear on the legs or arms, less often on the stomach, chest or face. After the destruction of the node, areas of atrophy of adipose tissue are observed in its place, which outwardly look like retraction of the skin.

In some cases, before the appearance of nodes, patients experience symptoms characteristic of the flu - weakness, muscle pain, headache, etc.

Plaque form

Plaque panniculitis is manifested by the formation of multiple nodes, which quickly grow together to form large conglomerates. In severe cases, the conglomerate spreads to the entire area of the subcutaneous tissue of the affected area - shoulder, thigh, lower leg. In this case, the compaction causes compression of the vascular and nerve bundles, which causes swelling. Over time, lymphostasis may develop due to impaired lymph flow.

Nodal form

With nodular panniculitis, nodes with a diameter of 3 to 50 mm are formed. The skin over the nodes takes on a red or burgundy hue. The nodes are not prone to fusion in this variant of the disease.

Infiltrative form

In this variant of the development of panniculitis, melting of the resulting conglomerates with the formation of fluctuations is observed. Externally, the lesion looks like phlegmon or an abscess. The difference is that when the nodes are opened, there is no discharge of pus. The discharge from the node is a yellowish liquid with an oily consistency. After opening the node, an ulceration forms in its place, which does not heal for a long time.

Visceral form

This option Panniculitis is characterized by damage to the fatty tissues of internal organs. Such patients develop pancreatitis, hepatitis, nephritis, and characteristic nodes may form in the retroperitoneal tissue.

Diagnostic methods

Ultrasound of internal organs is also prescribed for diagnosis.

Diagnosis of panniculitis is based on studying the clinical picture and conducting tests. The patient should be referred for examination to specialists - nephrologist, gastroenterologist, rheumatologist.

The patient will need to donate blood for biochemistry, liver tests, and conduct a study of enzymes produced by the pancreas. As a rule, an ultrasound scan of internal organs is prescribed.

To exclude the septic nature of the lesion, the blood is checked for sterility. For staging accurate diagnosis a biopsy of the node is performed.

Treatment regimen

Treatment of panniculitis is selected individually, depending on the course and form of the disease. Treatment must be comprehensive.

As a rule, patients with nodular panniculitis occurring in chronic form, appoint:

Nonsteroidal drugs anti-inflammatory action.
Vitamins.
Injection of nodes with drugs containing glucocorticosteroids.

For infiltrative and plaque forms, glucocorticosteroids and cytostatics are prescribed. To support the liver, taking hepaprotectors is indicated.

For all forms, physical treatment is indicated - phonophoresis, UHF, laser therapy. Ointments with corticosteroids are used locally.

With secondary fatty granuloma, it is necessary to treat the underlying disease.

Treatment with traditional methods

Additionally, herbal medicine can be used. Useful for panniculitis:

Compresses from raw beets to the affected area.
Compresses from crushed hawthorn fruits.
Compresses made from crushed plantain leaves.

Good to drink herbal teas, prepared on the basis of echinacea, rose hips, eleutherococcus for general strengthening of the body.

Prognosis and prevention

Since the mechanism of development of primary panniculitis is unclear, there is no specific prevention of this disease. To prevent a secondary form of the disease, it is necessary to actively and persistently treat the underlying disease.

In chronic and subacute forms of the disease, the prognosis is favorable. In the acute version of the disease, it is extremely doubtful.

Panniculitis is a progressive inflammation of the subcutaneous fatty tissue, which leads to the destruction of fat cells, their replacement with connective tissue with the formation of plaques, infiltrates and nodes. In the visceral form of the disease, damage occurs to the fat cells of the pancreas, liver, kidneys, fatty tissue of the retroperitoneal region or omentum.

Approximately 50% of cases of panniculitis occur in the idiopathic form of the disease, which is more common in women between 20 and 50 years of age. The remaining 50% are cases of secondary panniculitis, which develop against the background of skin and systemic diseases, immunological disorders, and the action of various provoking factors (certain medications, cold). The development of panniculitis is based on a violation of lipid peroxidation.

Causes

Panniculitis can be caused by various bacteria (usually streptococci, staphylococci).

Panniculitis in most cases develops on the legs. The disease can occur after injury, fungal infection, dermatitis, or ulcer formation. The most vulnerable areas of the skin are those with excess fluid (for example, swelling). Panniculitis can occur in the area of postoperative scars.

Symptoms of panniculitis

The main symptom of spontaneous panniculitis is nodular formations that are located in the subcutaneous fat at different depths. They usually appear on the arms, legs, and less often on the face, chest, and abdomen. After the nodes resolve, areas of fatty tissue atrophy remain, looking like round areas of skin retraction.

The nodular variant is characterized by the appearance of typical nodes ranging in size from 3 mm to 5 cm in the subcutaneous tissue. The skin over the nodes can have a color from normal to bright pink.

The plaque version of panniculitis is characterized by the appearance of separate clusters of nodes that grow together and form bumpy conglomerates. The skin over such formations may be pink, burgundy or burgundy-bluish. In some cases, clusters of nodes spread to the entire tissue of the thigh, leg or shoulder, compressing nerve and vascular bundles. This causes severe pain, swelling of the limb, and the development of lymphostasis.

The infiltrative variant of the disease occurs with the melting of nodes and their conglomerates. The skin in the area of the plaque or node is burgundy or bright red. Next, a fluctuation appears, characteristic of phlegmons and abscesses, but when the nodes are opened, it is not pus that is released, but an oily yellow mass. A long-term non-healing ulcer remains at the site of the opened node.

The mixed version of panniculitis is a transition from a nodular form to a plaque form, and then to an infiltrative one. This option is rare.

At the onset of the disease, headaches, fever, general weakness, pain in muscles and joints, and nausea are possible.

The visceral form of the disease is characterized by systemic damage to fatty tissue throughout the body with the development of nephritis, hepatitis, pancreatitis, and the formation of characteristic nodes in the omentum and retroperitoneal tissue.

Panniculitis can last from 2-3 weeks to several years.

Diagnostics

Diagnosis of panniculitis includes examination by a dermatologist together with a nephrologist, gastroenterologist, and rheumatologist.

Blood and urine tests, pancreatic enzyme tests, liver tests, and the Rehberg test are used.

Detection of nodes in visceral panniculitis is carried out using ultrasound examination of the abdominal organs and kidneys.

Blood culture for sterility helps to exclude the septic nature of the disease.

An accurate diagnosis is established based on the results of a biopsy of the node with histological examination.

Classification

There are spontaneous, primary and secondary forms.

Secondary panniculitis includes:

Immunological panniculitis - often occurs against the background of systemic vasculitis;

Lupus panniculitis (lupus panniculitis) - with a deep form of systemic lupus erythematosus;

Enzymatic panniculitis - associated with the effects of pancreatic enzymes in pancreatitis;

Proliferative cell panniculitis - with leukemia, histiocytosis, lymphoma, etc.

Cold panniculitis - local form, developing in response to cold exposure;

Steroid panniculitis - occurs in children after completion of corticosteroid treatment;

Artificial panniculitis - associated with the administration of medications;

Crystalline panniculitis - develops with gout, renal failure as a result of deposition of urates, calcifications in the subcutaneous tissue, as well as after injections of pentazocine, meneridine;

Panniculitis associated with α1-antitrypsin deficiency (hereditary disease).

Based on the shape of the nodes formed during panniculitis, infiltrative, plaque and nodular variants of the disease are distinguished.

Patient Actions

At the first symptoms of panniculitis, you should consult a doctor. In addition, you should seek medical help if, during the treatment of the disease, new symptoms are unexpectedly discovered (constant fever, increased fatigue, drowsiness, blisters, increased redness).

Treatment panniculitis

Treatment of panniculitis depends on its form and course.

For nodular panniculitis with a chronic course, non-steroidal anti-inflammatory drugs (diclofenac sodium, ibuprofen, etc.), antioxidants (vitamins C, E) are used, and nodular formations are injected with glucocorticoids. Physiotherapeutic procedures are also effective: ultrasound, hydrocortisone phonophoresis, laser therapy, UHF, magnetic therapy, ozokerite.

For infiltrative and plaque forms, subacute panniculitis, glucocorticosteroids (prednisolone, hydrocortisone) and cytostatics (methotrexate) are used.

Treatment of secondary forms of the disease includes therapy for the underlying disease: systemic lupus erythematosus, pancreatitis, gout, vasculitis.

Complications

Abscess;

Phlegmon;

Gangrene and skin necrosis;

Bacteremia, sepsis;

Lymphangitis;

Meningitis (if the facial area is affected).

Prevention panniculitis

Prevention of panniculitis consists in timely diagnosis and treatment of primary diseases - fungal and bacterial infection, vitamin E deficiency.

Federal State state-financed organization"Research Institute

Rheumatology" RAMS, Moscow

Federal State Budgetary Institution "Scientific Research Institute for Rheumatology" RAMS, Moscow

Contacts: Olga Nikolaevna Egorova [email protected]

Contact: Olga Nikolayevna Egorova [email protected]

Received 11/28/11

Spontaneous panniculitis: modern approaches to treatment

HE. Egorova, B.S. Belov, Yu.A. Karpova

Spontaneous panniculitis (SP; synonym: idiopathic lobular panniculitis, idiopathic Weber-Christian panniculitis, febrile recurrent non-suppurating panniculitis, lipodystrophy, nodular panniculitis, etc.) is a rare and poorly understood disease that is characterized by recurrent necrotic changes subcutaneous fatty tissue (SFA), as well as damage to internal organs.

Women aged 20-50 years are most often affected. According to International classification diseases of the 10th revision of the SP refers to systemic lesions of connective tissue (M 35.6)

The term “panniculitis” was first proposed by J. Salin in 1911. However, somewhat earlier, in 1892, V. Pfeifer first described the “syndrome focal dystrophy» PZhK with localization of nodes on the cheeks, mammary glands, upper and lower limbs, which was accompanied by progressive weakness. N. Christian (1928) drew attention to the presence of fever in this disease. In 1936, I. Brill proposed a new term - “Pfeiffer-Weber-Christian disease.” In the domestic literature, SP was first described by Yu. V. Postnov and L. N. Nikolaeva (1961). Largest number observations (60 patients) in our country belongs to E.V. Verbenko, who highlighted the main clinical forms diseases. IN last years About 200 cases of SP have been described in the world literature and 50 in the domestic literature.

Despite a long period study, currently there is no single concept of the etiology and pathogenesis of this disease. The immunopathological nature of the disease is assumed, the provoking factors of which may be trauma, disorders of fat metabolism and endocrine system, damage to the liver and pancreas, the influence of bromine and iodine preparations.

The most important role in the pathogenesis of SP belongs to disturbances in the processes of lipid peroxidation. Highly toxic intermediate oxidation products that accumulate in organs and tissues inhibit the activity of a number of enzymes and change permeability cell membranes, thereby causing degeneration of cellular structures, and then cytolysis, which correlates with the severity of the clinical manifestations of SP. They also report high levels of circulating

ruining immune complexes, causing damage PZHK. The role of pro-inflammatory cytokines in the genesis of SP is discussed. It has been shown that in SP, activated macrophages and lymphocytes produce increased amount interleukin 2 (IL2) and tumor necrosis factor a (TNFa). The latter is considered a key cytokine involved in the development of the disease. German researchers have identified a mutation in the THK81A gene (R92Q, T50M) in association with increased serum TNF titers in SP.

The disease is characterized by the rapid development of limited subcutaneous nodes located in the pancreas at different depths, usually multiple, with predominant localization on the lower and upper limbs, less often on the chest, abdomen and face. Usually, within a few weeks, the nodes resolve, leaving “saucer-shaped” recesses of the skin due to the development of atrophy of the pancreas, in which calcium salts are sometimes deposited.

Depending on the shape of the node, SP is divided into nodular, plaque and infiltrative. At knotty shape the nodes are clearly demarcated from the surrounding tissue, their color, depending on the depth of occurrence, varies from the color of normal skin to bright pink, and the diameter of the compaction ranges from a few millimeters to 5 cm or more (Fig. 1). The plaque variety is the result of the fusion of individual nodes into a dense elastic lumpy conglomerate, the color of the skin over it varies from pink to bluish-purple (Fig. 2). The infiltrative variant is characterized by the occurrence of fluctuations in the zone of individual nodes or conglomerates of a bright red or purple color; the opening of the lesion occurs with the release of a yellow oily mass (Fig. 3).

The duration of the disease varies from several weeks to several years. The course can be benign and is limited only to skin manifestations. In the systemic variant of the disease, the pancreas of the retroperitoneal region and omentum is involved in the pathological process (mesenteric panniculitis), hepatosplenomegaly, pancreatitis, nephropathy are detected, which is not always accompanied by skin symptoms. In some cases, the development of SP is preceded by fever (up to 41 °C), mild

pain, nausea, vomiting, loss of appetite, polyarthralgia, arthritis and myalgia.

There are acute, subacute and recurrent variants of the course. Acute SP is rare, with general symptoms ( prolonged fever hectic type, progressive weakness) increase rapidly, body temperature does not decrease, despite the use of antibiotics, glucocorticoids (GC), cytotoxic drugs and symptomatic remedies. This variant is characterized by severe myalgia, polyarthralgia and arthritis, changes in blood tests (including biochemical indicators of liver and kidney function) and urine. In the terminal stage, disorders of the blood coagulation system develop. Remissions occur rarely and their duration is short (1-3 months). With each new relapse, the patient’s condition progressively worsens, the disease ends in death within a period of 3 months to 1 year.

The subacute course is characterized by pronounced general symptoms of the disease, leukopenia, increased ESR, and changes in the enzymatic activity of the liver. This variant is characterized by torpidity and resistance to therapy.

Rice. 1. Knotty form of the joint venture (here and in Fig. 2, 3 - own observations)

The chronic (recurrent) process is characterized by a favorable prognosis, regardless of the severity of the onset, as well as long-term remissions and mild relapses. General state usually does not change. Physical pathological symptoms from the internal organs are absent in most cases, only in biochemical analyzes blood signs are revealed functional failure liver.

For visceral forms with severe course death noted in 10% of cases.

Atypical variants of SP include a febrile form of skin lesions (in the absence of visceral pathology) with long-term non-healing ulcers, resistant to therapy, developing mainly in adolescents. This variant of SP was described by M. Yaostapp and E. Makai in 1894 (Rothman-Makai syndrome). Less common is Dercum's disease, which is characterized by painful, slowly developing infiltrates in the pancreas in the form of limited nodes or diffuse thickenings, observed in persons with metabolic or endocrine system disorders (obesity, menopause, disorders menstrual cycle, hypothyroidism, etc.).

Rice. 2. Plaque form of SP

Rice. 3. Infiltrative form of SP (a, b) Nauch-practical rheumatol 2012; 54(5): 110-114

Thus, we can identify a triad of characteristics characteristic of SP:

Fever,

The presence of painful subcutaneous nodes on the trunk and limbs,

Tendency to relapse.

The diagnosis of SP is based on the characteristic clinical picture and data from histological examination of the node biopsy (signs of lobular panniculitis).

Treatment for SP has not been fully developed and is carried out mainly empirically. Nonsteroidal anti-inflammatory drugs (NSAIDs), small doses of GCs and aminoquinoline drugs help reduce the severity of inflammatory changes, in particular in the nodular form and chronic course of the disease. In case of single nodes, a good therapeutic effect is observed from the administration of GC by puncturing the lesions without the development of atrophy of the pancreas. At the same time, course doses of GC are significantly lower than when taken orally.

For the treatment of various forms of SP in the twentieth century. antibiotics were used, mainly penicillin and tetracycline. Subsequently, it was found that the use of these drugs does not affect the course of SP. During bacteriological and morphological examination of discharge from nodes, the pathogen, as a rule, is not detected. However, for Rothman-Makai syndrome, the possibility of using tetracyclines (minocycline hydrochloride 200 mg/day) is being considered, given their in vitro inhibitory effect on pancreatic lipase activity.

Physiotherapeutic procedures are also used on the area of the nodes: phonophoresis with 2.5-5% hydrocortisone, lidase, ozokerite applications, 50-60% dimexide, ultrasound, magnetic and UHF therapy, as well as exposure to laser beams directly on the lesions.

In the nodular or plaque form of acute or subacute course It is advisable to prescribe GC in medium doses and various cytostatic drugs (CP) - cyclophosphamide, methotrexate (MTX), azathioprine. There are a number of publications devoted to the successful use of the listed CPs in individual patients, but clear indications, doses and treatment regimens are currently lacking.

Big problems arise during the treatment of the infiltrative form of systemic SP. In these cases, even therapy with megadoses of GC in combination with CP does not always lead to success.

One of the most promising drugs for the treatment of SP appears to be cyclosporine A (CsA). It is known that this drug has the ability to selectively inhibit the expression of genes involved in the early activation of T lymphocytes and the transcription of mRNA of certain cytokines, including IL2, IL3, IL4, interferon γ (IFU). Important point applications of CsA - partial blocking of the expression of membrane IL2 receptors on T lymphocytes. Compared with other immunosuppressive drugs, CsA is generally less likely to cause serious adverse events such as infectious complications and malignant neoplasms.

The successful use of CsA in SP was first reported by P. Entzian et al. in 1987. Subsequently, the effectiveness of this drug was demonstrated in case reports of SP by other researchers.

G. Pongratz et al. provide a description of a case of the development of acute nodular SP in a 14-year-old patient who was seropositive rheumatoid arthritis, against the background of treatment with MT in combination with leflunomide and then sulfasalazine. Prescription of prednisolone (80 mg/day) and CsA (3.0 mg/kg/day) for 1 month led to regression of skin pathology.

b. SaPapt et al. We observed an 8-year-old child suffering from a plaque form of SP in combination with vasculitis of small vessels. During the examination we excluded infectious diseases bacterial and viral etiology, as well as systemic diseases connective tissue. Therapy with prednisolone at a dose of 1 mg/kg per day led to a decrease in the severity of pain and skin changes, but did not affect the progression of the disease. The administration of CsA at a dose of 5 mg/kg per day made it possible to stabilize the inflammatory process.

M. Hinata et al. reported the successful use of CsA in a 37-year-old man who suffered from systemic liver disease, manifested by recurrent nodes in the pancreas of the lower extremities, fever, pleurisy, liver damage with the development of ascites and a marked increase in transaminases and alkaline phosphatase in blood serum. The diagnosis of SP was confirmed when histological examination biopsy samples of the subcutaneous node and liver. Pulse therapy with methylprednisolone at a total dose of 3 g was unsuccessful. The condition progressively worsened with the development of severe jaundice, gastrointestinal bleeding, high levels of total bilirubin and the soluble form of the IL2 receptor in the blood. Plasma transfusion was prescribed and parenteral administration CsA (100 mg/day intravenously) with a further (after 3 weeks) transition to oral administration of the drug at a dose of 225 mg/day. As a result of the therapy, a pronounced clinical improvement was noted, accompanied by obvious positive dynamics in the liver, which was confirmed by repeated histological examination of its biopsy (reduction of inflammatory cell infiltration and signs of periportal steatohepatitis, as well as repair of small bile ducts). During the 5-year observation period, no exacerbations of SP were observed.

TN. Suchkova et al. observed a 16-year-old patient who skin manifestations were of a widespread recurrent nature with ulcerations and the release of caseous oily masses, which was accompanied by fever (37-40 ° C) and headaches. The morphological picture of the skin biopsy was consistent with the diagnosis of Weber-Christian panniculitis. As a result of the examination, the following were excluded: panniculitis associated with α1-antitrypsin deficiency, enzymatic panniculitis, indurative erythema, systemic vasculitis. Antibacterial and anti-inflammatory therapy led to short-term improvement. CsA was prescribed at a dose of 200 mg/day for 18 days in combination with ceftriaxone, suprastin, diclofenac. The patient was discharged with improvement under the supervision of a dermatologist.

Other Russian authors have reported the successful use of CsA in the generalized form of SP in a child early age against the background of residual encephalopathy with hypertensive-hydrocephalic syndrome, combined with hepatosplenomegaly, diffuse parenchymal and ductal changes in the liver

nor, multicystic kidney disease, endomyocarditis, left ventricular fibrosis.

Work on studying the effectiveness and tolerability of mycophenolate mofetil (MMF) in patients with SP deserves undoubted attention. MMF is a drug with selective immunosuppressive activity and causes reversible inhibition of DNA synthesis and proliferation of stimulated T and B lymphocytes, without affecting most dividing cells of other types. It has been shown that mycophenolic acid (a product formed under the influence of hepatic esterases after taking MMF) inhibits the formation of antibodies, activation of monoclonal cells, excess production of collagen and other matrix proteins, and reduces the production of TNFa and IL1.

One of the first publications devoted to the use of MMF in this pathology is the work of German authors who observed three patients with the infiltrative form of SP. At the same time, two patients had signs of mesenteric panniculitis, confirmed by magnetic resonance imaging (MRI). Initial therapy with prednisolone (1.5 mg/kg body weight per day) led to an improvement in the condition in two patients, but when trying to reduce daily dose GC observed a relapse of the disease in both cases. In one patient, no effect from the GC therapy was noted. At the next stage, along with increasing the daily dose of prednisolone to 2 mg/kg body weight, azathioprine 1.5 mg/kg per day (two patients who responded to initial therapy) or MT 50 mg per week (one patient who did not respond) was added to treatment for treatment). During the therapy, an improvement in the condition was noted, but repeated attempts to reduce the daily dose of GC led to a relapse of the disease in all cases. Treatment with azathioprine and MTX was stopped and MMF was prescribed at a dose of 2 g/day. After 2 weeks, normalization of ESR and CRP levels was observed, after which they began gradual decline daily dose of GC until complete withdrawal. A repeat MRI revealed complete reverse development re-troperitoneal changes. Over a 6-10 month period, the dose of MMF was reduced to 1 g/day in two patients. Signs of activation of the process were not observed in any case.

E.V. Vawkap et al. reported the successful use of MMF as monotherapy in the infiltrative form of SP. A 45-year-old woman suffered from widespread non-healing ulcers with oily discharge on the upper and lower extremities for 7 months, which was accompanied by fever, arthritis and general weakness. The diagnosis of SP was confirmed by morphological examination of the node. Considering the recurrent nature of the disease, she was prescribed prednisolone at a dose of 15 mg/kg per day for 3 months, but an ulcer developed duodenum, skin changes recurred against the background of fever and continued high laboratory activity (ESR 42 mm/h, CRP 4.66 mg/dl). Torpidity of the disease and development adverse reactions during GC therapy served as justification for prescribing MMF at a dose of 2.0 g/day. During the 1st month of treatment, the ulcerations gradually regressed with the formation of scars, repeated skin formations not noted ESR indicators and CRP returned to normal. By the end of the 2nd month of therapy, the dose of MMF was reduced to 1.5 g/day. At the moment

A second examination after 3 months of observation revealed remission of the disease.

Considering the supposed key pathogenetic role of pro-inflammatory cytokines, primarily TNF-α, there are quite good reasons to believe that inhibition of the latter using monoclonal antibodies could have a significantly greater impact on the course of the immunopathological process in SP compared to therapy with GC and CP.

R. BashresM et al. We observed two patients with SP associated with a mutation in the TNFRSF1A gene. A 66-year-old woman with recurrent fever, multiple skin indurations, oligoarthritis and high laboratory values of inflammatory activity was diagnosed with SP, confirmed by morphological examination. The patient’s two sisters had a similar symptom complex. Additional examination revealed antineutrophil cytoplasmic antibodies, but there were no clinical manifestations of systemic vasculitis. Therapy with colchicine, gold salts, MT, leflunomide and azathioprine was unsuccessful. The administration of etanercept at a dose of 25 mg subcutaneously 2 times a week allowed to stabilize the patient’s condition. A 53-year-old patient had a similar clinical symptoms with severe abdominal syndrome and myalgia, accompanied by high levels of inflammatory activity. Histological examination confirmed the diagnosis of mesenteric SP. Attempts to reduce the daily dose of GC, which was 50 mg, were accompanied by exacerbations of the process. The therapy undertaken with a genetically engineered biological drug from the group of TNF-α inhibitors etanercept at a dose of 50 mg/week allowed to achieve remission of the disease.

Greek researchers presented a case of SP that developed in a 29-year-old woman and occurred with ptosis, edema of the periorbital region and a progressive decrease in visual acuity in both eyes. Considering the lack of effect from the therapy with GC (16 mg/day) and MT (12.5 mg/week), the authors used infliximab (INF) at a dose of 5 mg/kg per administration. This resulted in improved visual acuity and a significant reduction in ptosis and swelling in the right eye. However, after the fourth injection of the drug, an allergic reaction developed, and therefore INF was replaced with adalimumab. The administration of the latter at a dose of 40 mg once every 2 weeks for 2 years made it possible to reduce the dose of GC to 8 mg/day and achieve normalization of body temperature, as well as stabilization of skin symptoms. However, left-sided enophthalmos persisted throughout the observation period.

A case of successful use of INF in a 54-year-old patient with systemic SP was demonstrated by E A1-Nat et al. . For several years, the patient noted recurrent widespread lumps on the thighs and abdomen, fever, myalgia, arthralgia, nausea and abdominal pain. These symptoms were regarded as manifestations of cellulite, for which antibacterial therapy which was ineffective. Histological examination of skin biopsies revealed typical signs of lobular panniculitis. The use of GCs either orally or in the form of pulse therapy with cyclophosphamide was not successful. The administration of Imur-na was accompanied by the development of nausea and an increase in

transaminase levels. Three-time use of INF at a dose of 5 mg/kg (0, 2 and 6 weeks) in combination with GC (10 mg/day) significantly reduced the clinical manifestations of the disease and normalized laboratory activity parameters. During the 14-month follow-up period, there was stable remission diseases.

As follows from the above, the use of TNF-α inhibitors in the infiltrative form of SP, resistant to initial therapy with GCs and cytostatics, seems justified and can significantly improve the prognosis of the disease.

It is recommended to include the active antioxidant vitamin E in the complex treatment of all forms of joint venture throughout the year. Carrying out surgical interventions In any form of SP, it is considered inappropriate and contributes to the progression of the disease.

Thus, based on the analysis of the still sparse literature data, the leading principles of treatment for patients with SP appear to be the following:

Achieving remission or at least reducing the duration and severity of the inflammatory process;

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In the nodular form of the chronic course, it is advisable to use NSAIDs in combination with aminoquinoline drugs and physiotherapeutic procedures;

Nodular and plaque forms, occurring acutely or subacutely, require early administration of GC and cytotoxic drugs (cyclophosphamide, azathioprine);

In the infiltrative form of SP, “selective” cytostatics (CsA, MMF), prescribed for a 6-month period in combination with GCs, can be considered as the drugs of choice; if this regimen is ineffective, the issue of prescribing genetically engineered biological drugs - TNF inhibitors should be resolved

It must be emphasized that great importance in the management of patients with SP is the prevention of relapses, which consists of sanitizing foci of infection, preventing injuries, including post-injection injuries, bruises, colds, excessive insolation, as well as compliance hypoallergenic diet with limited fats and carbohydrates.

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24. Prokhorenkov V.I., Guzey T.N., Gasich N.A. and others. A case of Weber-Christian panniculitis in a young child.

Vestn Dermatol Venerol 2004;2:34-7.

25. Zollinger H.W. Mycophenolate in transplantation. Clin Transplant 2004;18:485-92.

26. Enk A.H., Knop J. Treatment of relapsing idiopathic nodular panniculitis (Pfeifer-Weber-Christian disease) with mycophenolate mofetil. J Am Acad Dermat 1998;39(3):508-9.

27. Baskan E.B., Saricaoglu H., Tunali S., Tolunay S. Effective treatment of relapsing idiopathic nodular panniculitis (Pfeifer-Weber-Christian disease) with mycophenolate mofetil.

J Dermatol Treat 2003;14:57-60.

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29. Al-Niaimi F., Clark C., Thorrat A., Burden A.D. Idiopathic lobular panniculitis: remission induced and maintained with infliximab. Br J Dermatol 2009;161:691-2.