A patient with Pfeifer-Weber-Christian disease--successful therapy with cyclosporin A: case report.

BACKGROUND: Pfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article. CASE PRESENTATION: We here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patient's symptoms resolved. CONCLUSION: Our observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.

Small vessel vasculitis and relapsing panniculitis in tumour necrosis factor receptor associated periodic syndrome (TRAPS).

CASE REPORTS: A 66 year old female patient had relapsing fever and non-suppurative panniculitis suggestive of enigmatic "Weber-Christian disease" (WCD). Antineutrophil cytoplasmic antibodies with specificity for human leucocyte elastase (HLE-ANCA) were detected. A biopsy showed small vessel vasculitis and panniculitis. A 53 year old man had recurrent episodes of abdominal pain, erythematous rash, and myalgia. Fever attacks had stopped a few years ago. A biopsy showed panniculitis and fasciitis. In both patients mutations (R92Q, T50M) of the tumour necrosis factor receptor super family (TNFRSF) 1A gene were disclosed. Mutations of the TNFRSF 1A gene are the cause of tumour necrosis factor receptor associated periodic syndrome (TRAPS). Both patients responded favourably to treatment with the human soluble p75 TNF alpha receptor fusion protein etanercept (2 x 25 mg subcutaneously/week). DISCUSSION: Small vessel vasculitis and panniculitis have not been reported in TRAPS so far. The cases underline the importance of TNF alpha regulation in inflammatory processes including vasculitis. Genetically determined causes of fever may account for some cases of WCD.

Systemic Weber-Christian disease complicated by partial transverse myelopathy.

Weber-Christian disease is an inflammatory disorder of fatty tissue which usually presents with raised red tender nodules in the skin. Although there may be additional systemic upset, there are very few reports of neurological features associated with this condition. We report a patient with biopsy-confirmed systemic Weber-Christian disease in whom a transient partial myelopathy, of probable inflammatory origin, was the most prominent feature. Based on recent reports of the effects of immune mediators on neuronal function, a possible pathogenetic explanation for this syndrome is suggested.

Successful treatment of a patient with febrile, lobular panniculitis (Weber-Christian disease) with oral cyclosporin A: implications for pathogenesis and therapy.

We report a 15-year-old Japanese girl with severe systemic Weber-Christian disease (WCD) who presented with acute onset of high fever associated with tender subcutaneous nodules. Laboratory tests showed an elevated serum concentration of lactate dehydrogenase (LDH), leukopenia, and coagulation abnormalities. The anti-nuclear and anti-DNA antibodies were negative, and the serum pancreatic enzymes and alpha 1-antitrypsin levels were normal. Pulse steroid therapy was not effective, and eventually cerebellar hemorrhage occurred. After initiation of oral cyclosporin A (CyA) therapy, fever came down and her clinical condition improved markedly. Extremely high serum concentrations of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R) in this patient returned to normal with CyA therapy. These findings suggest that T-cell immune responses are involved in the pathogenesis of WCD, and that CyA is effective against the disease via suppression of T-cell reactions.

Systemic Weber-Christian disease with reversible bilateral ureteric obstruction.

It has been proposed that idiopathic retroperitoneal fibrosis may be a consequence of 'healed' retroperitoneal lesions of systemic Weber-Christian disease. However ureteric obstruction which is the hallmark of idiopathic retroperitoneal fibrosis, has not been described in systemic Weber-Christian disease. We report a patient with systemic Weber-Christian disease who, during a relapse, developed bilateral ureteric obstruction which resolved when the Weber-Christian disease remitted. The radiological appearances were consistent with a diagnosis of idiopathic retroperitoneal fibrosis, but the clinical course was slightly atypical in that the ureteric obstruction resolved completely and rapidly. Ureteric obstruction can complicate systemic Weber-Christian disease and this observation gives support to the hypothesis that idiopathic retroperitoneal fibrosis is related to systemic Weber-Christian disease.

Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia.

Repeated episodes of febrile panniculitis and hepatitis were the main clinical features in two patients with an IgG1 kappa paraproteinemia and severe depletion of the early components of the classical pathway of complement (acquired C1 inhibitor deficiency). They did not have episodes of cutaneous angioedema or evidence of immune complex disease. In the more severely affected patient, the episodes responded to steroids. These features have not been described with acquired C1 inhibitor deficiency and may be related to complement activation.

Suppressor-cytotoxic T-lymphocyte panniculitis.

A 3 1/2-year-old girl had fever and nonsuppurative panniculitis. Biopsies revealed lobular lymphocytic panniculitis. An extensive evaluation of the patient for infectious and other systemic diseases yielded negative results. Although the number of peripheral T lymphocytes was normal, suppressor-cytotoxic (OKT8) lymphocytes predominated in the subcutis of the lesions. Suppressor-cytotoxic T-lymphocyte panniculitis may represent a unique type of panniculitis.

Weber-Christian panniculitis and chronic active hepatitis.

We report a 4-year-old child with Weber-Christian panniculitis who subsequently developed histologically proven chronic active hepatitis, pancreatitis and extensive lipoatrophy. An "LKM" variant autoantibody was detected in the serum and a favourable response has been seen with immunosuppressive therapy. These findings lend support to the concept of Weber-Christian being an "auto-immune" disease.

Lupus erythematosus panniculitis with partial genetic deficiency of C2 and C4 in a child.

A 7-year-old girl developed recurrent febrile nodules and subcutaneous plaques on her arm, shoulder, and face. Primary acquired toxoplasmosis was diagnosed at onset, because of associated lymphadenopathy and detection of specific IgM. Skin lesions were responsive to therapy with systemic steroids but progressed to atrophy and poikiloderma within a few months. Subsequently, chloroquine therapy has been instituted and no relapse has occurred. Histopathologic findings and direct immunofluorescence studies were diagnostic of lupus erythematosus panniculitis. Electron microscopy showed lamellar inclusions within mast cells. Results of laboratory investigations disclosed leukopenia and hypocomplementemia with low C2 serum levels. A family study of the complement system, including C4 and Bf phenotyping and HLA A, B, and DR haplotyping, revealed the carriage of both C2 and C4A null alleles in the propositus. This observation suggests an additional link between lupus erythematosus panniculitis and the remainder of the lupus erythematosus clinical spectrum.

Weber-Christian disease. Analysis of 15 cases and review of the literature.

We report 15 patients encountered over 13 years who presented with inflammation of subcutaneous fat and were given clinical and pathologic diagnoses of Weber--Christian disease (WCD). Prominent clinical features included female predominance, lower extremity nodules, fevers, arthritis/arthralgias, and myalgias. Notable laboratory features were elevated erythrocyte sedimentation rate, anemia, leukopenia, and hypocomplementemia, frequently with circulating 7S IgM or immune complexes at times of active symptoms. Histologic findings were lobular--together with frequent septal--panniculitis, fat-laden macrophages, variable cellular infiltrates, necrosis, and occasional vasculitis. Follow-up revealed the death of 2 patients and disease stabilization or improvement in 13 patients. Six patients developed features of other diseases (factitial disease, erythema nodosum, acute myelogenous leukemia, rheumatoid arthritis, systemic lupus erythematosus, and sarcoid) and a seventh may have had erythema induratum. We suggest that classic WCD, as originally described, reflects an increasingly recognized spectrum of panniculitides. These are syndromes of diverse etiology that share many clinical, inflammatory, and immunologic features.