Weber-Christian Disease

Panniculitis refers to a broad spectrum of diseases that involve inflammation of the subcutaneous fat layer of the skin. Weber-Christian disease is an eponym for a form of panniculitis, idiopathic nodular panniculitis, which is characterized by subcutaneous nodules, inflammatory cells in the fat lobules, and systemic symptoms.[1, 2] The nomenclature of this and other related diseases is confusing, and some authors believe that the eponym should be abandoned and that more specific diagnoses should be made on the basis of pathogenesis, cause, or additional diagnostic testing. The history of the eponym began in 1892 when Pfeifer first described the skin condition now known as Weber-Christian disease, or idiopathic lobular panniculitis. In 1925, Weber further depicted the syndrome[3] , and Christian emphasized the significance of fever as part of the syndrome. The syndrome became known as Weber-Christian disease in 1928.[4, 5]

Increasing study and diagnostic sophistication have differentiated Weber-Christian disease from diseases such as lupus panniculitis, factitial panniculitis, panniculitis associated with pancreatic disease, histiocytic cytophagic panniculitis, and alpha1-antitrypsin deficiency panniculitis.[6] With further differentiation, additional diseases will be distinguished from Weber-Christian disease. A review of 30 Mayo Clinic patients diagnosed with Weber-Christian disease stated that: "Because separate and distinct forms of fat lesions have been described, we believe that the eponym should be abandoned and the more specific diagnoses should be made on the basis of pathogenesis or cause."[7] At this time, the eponym Weber-Christian disease still refers to cases of nodular panniculitis with systemic signs and symptoms that remain idiopathic.

Weber-Christian disease is a classic skin condition that features recurring inflammation in the subcutaneous fat layer of the skin. The involved skin areas manifest as recurrent crops of erythematous, sometimes tender, edematous, subcutaneous nodules. Lesions distribution is symmetric, and the thighs and lower legs are affected most frequently. Malaise, fever, and arthralgias often occur. Nausea, vomiting, abdominal pain, weight loss, hepatomegaly, and additional systemic features may also occur. The key pathologic finding on microscopy is a nodular inflammatory pattern of the fat lobules. Because the etiology is unknown, Weber-Christian disease is often referred to as idiopathic lobular panniculitis.[8, 9]

Because its etiology is unknown, Weber-Christian disease is called idiopathic lobular panniculitis. Patients with Weber-Christian disease do not report a history of physical trauma.

In some patients with Weber-Christian disease, elevated levels of circulating immune complexes have been noted, suggesting an immunologically mediated reaction.[10]

Similarities between Weber-Christian disease and alpha1-antitrypsin deficiency suggest that an altered regulation of a normal inflammatory process may be involved.[5, 11] Responses to cyclosporine support a T-cell mediated inflammatory or autoinflammatory process.[12]

Infections and postviral infectious responses have been explored, and no connection has yet been established.[8, 13]

Frequency

United States

Ambiguity surrounding Weber-Christian disease versus other closely related conditions makes it difficult to determine the frequency of the diagnosis. It is recognized as a rare condition in adults and even more rare in pediatrics. White and Winkelmann's 1998 case record review of Weber-Christian disease at the Mayo Clinic found only 30 cases in a 28 year span between 1960 and 1998. They observed that cases of primary panniculitis are rare and that physicians may see only one or a few cases in a lifetime.[7]

International

The incidence and prevalence of Weber-Christian disease is unknown both in the United States and internationally. Weber-Christian disease is rare in adults and even rarer in children. For example, a chart review of children and adolescents in Brazil over a 20-year period (1983-2002) found 35 pediatric and adolescent cases of panniculitis, with only 6 cases meeting criteria for Weber-Christian disease.

Race

No racial predilection is reported.

Sex

Weber-Christian disease occurs more often in women, who comprise approximately 75% of reported cases. The disease is rare in the pediatric population, with a slight predilection for females over males. In the Moraes and colleagues Brazilian study, 4 of the 6 cases of Weber-Christian disease were girls.

Age

Weber-Christian disease may occur in children but is rare. It has been reported most frequently in people in the fourth to seventh decades of life, and 75% of cases occur in women after the second decade of life.[14]

Weber-Christian disease is a more serious form of panniculitis because of its systemic manifestations. The disease course varies, and prognosis depends on which organs are affected, the severity of organ involvement, and the response to therapy.

Weber-Christian disease may involve the lungs,[15] heart, intestines, spleen, kidney, adrenal glands, and even orbits.[16] Significant morbidity and mortality may occur in patients with inflammation involving visceral organs.

The clinical course in patients with only cutaneous manifestations may be characterized by exacerbations and remissions of the cutaneous lesions for several years before the disorder subsides.

Inform patients of the risks and adverse effects of various treatment options. Select different treatment modalities on an individual basis.

Patients with Weber-Christian disease present with cutaneous and systemic complaints. It is described as a relatively severe relapsing chronic condition.

Patients with Weber-Christian disease describe crops of lesions that appear and resolve during a period of weeks to months. The lesions are often symmetric in distribution, and the thighs and legs are most commonly involved. Individual nodules regress over the course of a few weeks.

Systemic symptoms of Weber-Christian disease include fever, malaise, nausea, vomiting, abdominal pain, weight loss, bone pain, myalgia, and arthralgia.

The etiology of Weber-Christian disease is unknown. Patients do not report a history of thermal, mechanical, or chemical trauma.

Physical examination reveals erythematous, edematous, and tender subcutaneous nodules. See the images below.

The nodules are usually symmetric and measure approximately 1-2 cm; however, nodules may be much larger. The lesions commonly occur on the thighs and lower legs, and may also involve the arms, trunk, and face.

Individual nodules resolve over a 2-week period, leaving an atrophic depressed scar.

Occasionally, the epidermis overlying the nodules breaks down, and the lesion discharges a brown liquid oil (ie, liquefying panniculitis).

Hepatomegaly or splenomegaly may be present in Weber-Christian disease in individuals with visceral involvement.

Although orbital Weber-Christian disease is rare, ophthalmologists need to be aware that patients with Weber-Christian disease can develop severe ocular inflammation.[17, 18]

Weber-Christian disease may involve the lungs, heart, intestines, spleen, kidney, and adrenal glands. Death may occur in patients with inflammation involving these critical visceral organs.

In patients with primarily cutaneous manifestations, the clinical course may be characterized by exacerbations and remissions of the cutaneous lesions for several years before the disorder subsides.

Changes in liver function test results, CBC count, and electrolyte levels reflect visceral involvement of organs, including the lungs, heart, intestines, spleen, kidneys, and adrenal glands in patients with Weber-Christian disease.

Patients may present with a leukocytosis or leukopenia, anemia, or hypocomplementemia.

The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) is usually elevated, although the degree of elevation varies.

Serum and urine amylase and lipase levels are within the reference range, differentiating Weber-Christian disease from a panniculitis associated with pancreatic disease.

The alpha1-antitrypsin level is within the reference range, differentiating Weber-Christian disease from alpha1-antitrypsin panniculitis.

A chest radiograph is used to exclude systemic inflammatory or infectious granulomatous diseases (eg, sarcoidosis or tuberculosis).

Skin biopsy is necessary to confirm the diagnosis of panniculitis.[19]

Lobular panniculitis

Idiopathic lobular panniculitis (Weber-Christian disease) presents without vasculitis and is shown in the images below.

Other conditions without vasculitis include the following:

• Histiocytic cytophagic panniculitis

• Alpha1-antitrpysin deficiency panniculitis

  Histopathologic features of alpha-1-antitrypsin deficiency panniculitis. (A) Scanning power shows a mostly lobular panniculitis. (B) Aggregations of neutrophils within the fat lobule are seen. (C) Neutrophils are interstitially arranged between collagen bundles of the deep reticular dermis. (A-C, hematoxylin-eosin stain; original magnifications: A, X 20; B, X 400; C, X 200).

• Physical panniculitis, including cold-induced, traumatic (shown in the image below), chemical-induced, and factitial (shown in the image below)

  Histopathologic features of late stage lesions of traumatic panniculitis. This lesion corresponds to the so-called nodular cystic fat necrosis or mobile encapsulated lipoma. A, Scanning power shows encapsulated and well-circumscribed lesion with no inflammatory infiltrate (arrow indicates area enlarged in B). B, At periphery of the lesion necrotic adipocytes appear as anucleated fat cells. (A and B, Hematoxylin-eosin stain; original magnifications: A, ×20; B, ×200.)

  Histopathologic features of paraffinoma. A, Scanning power shows a mostly lobular panniculitis (arrow indicates area enlarged in B). B, Higher magnification demonstrates cystic spaces within the fat lobule surrounded by foamy histiocytes. (A and B, hematoxylin-eosin stain; original magnifications: A, ×20; B, ×200.)

• Neonatal panniculitis, including sclerema neonatorum, neonatal subcutaneous fat necrosis (shown in the image below), and poststeroid panniculitis (shown in the image below)

  Histopathologic features of subcutaneous fat necrosis of the newborn. (A) Scanning power shows a mostly lobular panniculitis (arrow indicates area enlarged in B). (B) Higher magnification demonstrated narrow needle-shaped clefts radially arranged and surrounded by histiocytes. (A and B, hematoxylin-eosin stain; original magnifications: A, X 20; B, X 200).

  Histopathologic features of lipoatrophy secondary to subcutaneous injections of corticosteroids. (A) Low-power view showed small fat lobules (arrow indicates area enlarged in B). (B) Higher magnification demonstrates small adipocytes and prominent capillary proliferation, resembling embryonic fat. (A and B, hematoxylin-eosin stain; original magnifications: A, X 20; B, X 200).

• Lobular panniculitis of systemic disease, including pancreatic panniculitis, lupus erythematosus, sarcoidosis, calcifying panniculitis of renal failure, lymphoma and leukemia, and infections

Nodular vasculitis (erythema induratum) presents with vasculitis.

Septal panniculitis

Conditions without vasculitis include the following:

• Erythema nodosum

• Scleroderma panniculitis

• Lipodermatosclerosis

• Eosinophilic fasciitis

• Eosinophilic myalgia syndrome

Conditions with vasculitis include the following:

• Superficial migratory thrombophlebitis

• Polyarteritis nodosa

• Cutaneous polyarteritis nodosa

Histopathologic stages observed in Weber-Christian disease

The first stage is characterized by an acute inflammatory reaction, in which lobules of fat are replaced by neutrophils, lymphocytes, and histiocytes.

In the second stage, macrophages migrate and phagocytose degenerated fat, forming characteristic "foam cells."

In the third stage, the foam cells are replaced by fibroblasts, and the inflammatory reaction is replaced by fibrotic tissue.

No uniformly effective therapy for Weber-Christian disease is known. Clinical experience, especially in children and adolescents, has pointed to the value of corticosteroids and immunosuppressive agents.

Therapeutic responses have been reported with the use of fibrinolytic agents, hydroxychloroquine, azathioprine, thalidomide, cyclophosphamide, tetracycline, cyclosporine, mycophenolate, and clofazimine.

Systemic steroids (eg, prednisone) may be effective in suppressing acute exacerbations.

Nonsteroidal anti-inflammatory agents may reduce fever, arthralgias, and other signs of malaise.

Involvement of specific organs may require specific supportive drugs.

Inpatient hospitalization and supportive care may be necessary in severe cases of Weber-Christian disease in which inflammation involves visceral organs or for wound care, as indicated.

No surgical treatment is indicated.

Consultation with a pediatric dermatologist will help in considering differential diagnoses and possible causes of panniculitis. The dermatologist may also perform a skin biopsy for pathological review.

Consultation with a pediatric rheumatologist and infectious disease specialist will help to determine a differential diagnosis and implement a treatment regimen.

No specific dietary requirements are noted.

Activity is ad lib, and trauma to the affected areas should be avoided.

No effective methods of prevention have been discovered.

Monitor individuals with Weber-Christian disease for progression of the disease and for adverse effects of medications. Routine follow-up care is indicated.

No specific uniformly effective therapy for Weber-Christian disease is recognized. Therapeutic responses have been reported using fibrinolytic agents, hydroxychloroquine, azathioprine, thalidomide, cyclophosphamide, tetracycline, mycophenolate, and clofazimine. Systemic steroids (eg, prednisone) may be effective in suppressing acute exacerbations.[10, 20, 21, 22, 23]  Nonsteroidal anti-inflammatory agents (eg, indomethacin) may reduce fever, arthralgias, and other signs of malaise. Involvement of specific organs may require specific supportive drugs.

Class Summary

These agents are used for suppression of acute inflammatory exacerbations. These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Class Summary

These agents inhibit key factors that mediate immune reactions, which, in turn, decrease inflammatory responses. They may have potential long-term therapeutic response.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Cyclosporine (Neoral, Sandimmune)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, graft versus host disease) for a variety of organs. For children and adults, base dosing on ideal body weight. Demonstrated to be helpful in variety of skin disorders.

Cyclophosphamide (Neosar, Cytoxan)

Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Demonstrated to be helpful in various skin disorders.

Mycophenolate (CellCept)

Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

Hydroxychloroquine (Plaquenil)

Inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

Thalidomide (Thalomid)

Immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.

Class Summary

Several antibiotics (eg, tetracycline, clofazimine) are used for their anti-inflammatory activity.

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

Clofazimine (Lamprene)

Clofazimine is a lipophilic rhimophenazine dye that inhibits template function of DNA by binding to it. It is weakly bactericidal and has anti-inflammatory effects. Although the mechanism of action is unclear, it seems to exert its main effect on neutrophils and monocytes in various ways (eg, stimulating phagocytosis and release of lysosomal enzymes). Clofazimine is indicated for panniculitis of mycobacterial infections. It has been used in other inflammatory dermatoses but with unknown efficacy.

Use of clofazimine for the treatment of any disease other than leprosy is discouraged by the WHO and the manufacturer since indiscriminate use may promote emergence of resistant strains of M leprae.

Class Summary

These agents may reduce fever, arthralgia, and pain.

Indomethacin (Indocin)

Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.