Recurrent panniculitis: Weber-Christian disease

Abstract

Weber-Christian disease is characterized by recurrent inflammation in the fat layer of the skin. We report a boy, aged 2 years and 9 months, with Weber-Christian disease who presented with tender rounded swelling on the dorsum of both hands and chest wall with mild erythema in overlying skin associated with high grade continuous fever.

Introduction

Panniculitis refers to a broad spectrum of diseases that involve inflammation of the subcutaneous fat layer of the skin. Weber-Christian disease is a form of panniculitis called idiopathic nodular panniculitis ¹

Weber-Christian disease is characterized by subcutaneous nodules, recurrent inflammation in the fat layer of the skin, and systemic symptoms. The involved areas of the skin manifests as recurrent crops of erythematous, sometimes tender edematous subcutaneous nodules. ¹ Lesion distribution is symmetric, and the thighs and lower legs are affected most frequently. Malaise, fever, and arthralgia often occur. Nausea, vomiting, abdominal pain, weight loss, hepatomegaly, and additional systemic features may also occur. ¹ Weber-Christian disease may involve the lungs, heart, intestines, spleen, kidney, adrenal glands, and even orbits. ²

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. ³

The diagnosis of Weber-Christian disease is a diagnosis of exclusion. ⁴ It must be differentiated from systemic lupus, factitious, pancreatic associated,hostiocytic cytophagic and alpha 1 antitrypsin deficiency panniculitis. ⁵

Weber-Christian disease is an extremely rare condition in children. ⁶ 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. ⁷

As Weber-Christian disease is an extremely rare condition in children, we report this case of young boy, aged 2 years and 9 months, who presented to us with recurrent appearance of multiple painful swellings on legs, hands, face, and trunk associated with fever and generalized weakness and was diagnosed after extensive investigations and treated as Weber-Christian disease with marvelous improvement.

Case report

This case presentation was done after approval from ethical committee of research center of Tanta University and informed, signed consent from the parents of the child to participate in this case presentation.

Clinical history

A young boy, aged 2 years and 9 months, was admitted to the Pediatric Hematology Unit, Tanta University Hospital complaining of recurrent appearance of multiple painful swellings on the legs, hands, face, and trunk associated with fever and generalized weakness.

The condition started 8 months ago when the parents noticed tender rounded swelling on the dorsum of the left hand of their child with mild erythema in overlying skin associated with high-grade continuous fever not relieved by antipyretics, continuous crying, malaise, and refusal of feeding. They sought medical advice and the doctor prescribed medical treatment in the form of anti-inflammatory, local anti-edematous, ceftriaxone injection with no improvement after 3 days; the swelling increased in size and the pain increased with rise of fever up to 40°C, so they sought medical advice again and the doctor recommended incision with drainage and antibiotics for another week. The condition improved 3 days after drainage and the swelling subsided, but another painful swelling appeared on the dorsum of the other hand while the patient was under antibiotic therapy and drainage was done for the second swelling.

One month later, two other symmetrical swellings appeared on both feet and the child was admitted to another hospital. After full investigation and biopsy from the two swellings, the doctors recommended intravenous immunoglobulin (IVIG) but IVIG hypersensitivity occurred after two doses, and the child was admitted to the Intensive Care Unit for 1 week with clinical improvement.

Two days after discharge, the patient developed multiple symmetrical swellings on the leg, knee, and sub-mental region; the patient was admitted in Pediatrics Immunology Unit for 65 days for whom full investigations for immunological, rheumatological causes, pancreatitis, and Alpha one anti-trypsin deficiency were done and revealed no abnormal data. The patient was given medical treatment in the form of Maxipime, Vancomycin, and Diflucan.

Follow-up of the patient after that was done with dermatologist who treated him as chronic dermatitis with corticosteroid (2 mg/kg/day) and azathioprine (3 mg/kg/day) for 2 months. The condition improved with no appearance of any swellings during treatment, but relapse occurred after withdrawal of the treatment with the appearance of two new swellings in the dorsum of the right hand and the left cheek and the patient was admitted to the Pediatric Hematology Unit. The patient received Vancomycin, Diflucan, and Dapsone for 3 weeks with partial improvement and a few days later new crops of erythematous, edematous, tender nodules appeared again on the anterior chest wall and on the back.

Clinical examinations

General examination

The patient is conscious, alert, no abnormal facies, no special attitude in bed, and no abnormal gait. His pulse was 110 bpm, regular, average force, volume; equal in both sides, no special character, pulsations is felt in both lower limbs. Oral temperature was 37.5°C at the time of examination. The fever chart shows a fever up to 38.5°C once or twice daily on regular antipyretic drugs. Respiratory rate was 25 cycle/ minute and regular. Blood pressure was measured in four limbs with an average of 85/50 mmHg. The patient’s weight is 18 kg (90th percentile), his height is 95 cm (75th percentile), head circumference is 50 cm (50th percentile), and body mass index is 17.3 (75th percentile).

Head and neck examination

There was no pallor, no jaundice, no rash; there was a small rounded ill-defined swelling about 1 × 1 cm on the left cheek just below the zygoma, firm in consistency with normal skin color over the swelling and no signs of acute inflammation. No abnormal data were detected in the eye, ear, nose and tonsils, neck veins, no neck rigidity, and no palpable lymph nodes.

Extremities

There were scars of old incisions over the dorsum of both hands and feet; some of which are depressed and atrophied; and the others are hyper pigmented.

Chest wall examination

Chest wall examination revealed two well circumscribed masses in the anterior chest wall and three masses on the back of the chest, ovoid in shape, firm, mobile; tender with mild erythema in overlaying skin, no fluctuation, with a dimple in the center. The largest mass is about 10 × 8 cm. There were no abnormal finding in palpation, percussion, and auscultation of the chest.

Abdominal examination

Abdominal examination revealed: slight abdominal distension, right subcostal angle, inverted umbilicus, with no umbilical shift, no pigmentations, no dilated veins, no abdominal tenderness, lower border of the liver is palpable 1 cm below costal margin soft, not tender, upper border at right 5th intercostal space at mid-clavicular line, liver span is 10 cm, lower pole of spleen is just palpable below costal margin, firm in consistency, not tender, upper pole at 8th intercostal space at left mid axillary line. No ascites was detected clinically.

Heart and neurological examination

No abnormal data were found in the cardiovascular and neurological systems.

Investigations

Laboratory investigations

Complete blood count revealed microcytic hypochromic anemia with Hb 9.6 gm/dl, MCV 68 fl, MCH 24 pg, WBCs 4.8 ×10 ⁹/L, platelets 410 × 10⁹ with normal differential count on peripheral smear. ESR was 21/44 mm, CRP was 12 mg/L, ASOT was 165 IU/mL, negative antinuclear antibody and anti-double strand DNA, normal immunoglobulin assay including IgM 112 mg/dl (normal range, 40–230 mg/dl), IgA 91 mg/dl (normal range, 22–159 mg/dl), IgG 914 mg/dl (normal range, 441–1135 mg/dl), IgE 33.4 IU/mL (normal range <60 IU/mL), IgD 50 u/mL (normal <100 u/mL). Complement 3 was 154.9 md/dl (normal range, 77–195 mg/dl) and Complement 4 was 23 mg/dl (normal range, 9–40 mg/dl), serum amylase was 5.9 u/L (20 u/L), Alpha 1 antitrypsin was 142 mg/dl (normal range, 20–200 mg/dl). Nitro Blue Tetrazolium test was 53%, Anti-thrombin 3 was 62%, Protein C was 90%, Protein S was 84%, morning serum cortisol was 18.2 ug/dl, evening serum cortisol was 9.1 ug/dl, TORCH screening was negative. Serum creatinine was 0.4 mg/dl and blood urea was 18 mg/dl, serum protein was 7.79 g/dl and albumin was 4.9 g/dl, SGPT 26 unit/L and SGOT 16 unit/L, alkaline phosphatase 187 u/L, calcium 4.5 mg/dl, magnesium 2.3 mg/dl, sodium 139 m Eq/dl, potassium 3.5 mg/dl, and iron 32.3 ng/mL. Fungal and bacterial cultures from the swelling in both hands and feet revealed no growth. Histopathology: gross pathology of skin biopsy from dorsum of hand and foot showed panniculitis on acral part with oily discharge. Microscopic pathology of skin biopsy stained with (Hematoxylin and Eosin (H&E) ×100–200) showed neutrophilic panniculitis with basophilic degeneration of collagen with hemorrhage and necrosis of subcutaneous tissue, inflammatory cellular infiltrate (5 of 8 /HPF) which is mainly lymphocytes infiltrating all layers of skin and band of fibroblasts and inflammatory cells in bloody stroma with no vasculitis or malignant cells (Figure 1). Conclusion: histopathology of the examined skin biopsy favors the diagnosis of panniculitis with no vasculitis for differential diagnosis.

Figure 1.

Histopathology sections of skin biopsy stained with H&E (×100) (top) and fine needle aspiration biopsy stained with H&E (×200) (bottom) showing inflammatory cellular infiltrate (5 of 8 /HPF) which is mainly lymphocytes infiltrating all layers in the top figure and band of fibroblasts and inflammatory cells in bloody stroma in the bottom figure (arrows).

Pelvi-abdominal US

Apart from mild hepatosplenomegaly; no abnormal pelvic or abdominal sonographic findings were found.

Provisional diagnosis of our case is panniculitis for differential diagnosis with other causes of panniculitis including

• Polyarteritis Nodosa

• Sarcoidosis

• Systemic Lupus Erythematosus

• Vasculitis and thrombophlebitis

• Alpha 1 antitrypsin deficiency

• Weber-Christian disease.

Discussion

Panniculitis refers to a broad spectrum of diseases that involve inflammation of the subcutaneous fat layer of the skin. Weber-Christian disease is a form of panniculitis characterized by subcutaneous nodules, inflammatory cells in the fat lobules, and systemic symptoms. ⁸ The history of disease began in 1892 when Pfeifer first described it. In 1925, Weber further depicted the syndrome, ⁹ and Christian emphasized the significance of fever as part of the syndrome. The syndrome became known as Weber-Christian disease in 1928.^10,11

Weber-Christian disease is called idiopathic lobular panniculitis because its etiology is unknown; however, elevated levels of circulating immune complexes in some patients with Weber-Christian disease may suggest an immunologically mediated reaction, ¹² similarities between Weber-Christian disease and alpha 1-antitrypsin deficiency may suggest altered regulation of normal inflammatory process^11,13 and response to cyclosporine may support T-cell mediated inflammatory process. ¹⁴

Increasing study and diagnostic sophistication have differentiated Weber-Christian disease from lupus panniculitis, factitial panniculitis, panniculitis associated with pancreatic disease, histiocytic cytophagic panniculitis, and alpha 1-antitrypsin deficiency panniculitis. ¹⁵

• In our case, the absence of upper abdominal pain that radiates to the back, absence of abdominal tenderness, normal pancreas in abdominal sonar, and normal serum amylase level can differentiate Weber-Christian disease from panniculitis associated with pancreatic disease.

• The absence of jaundice and normal alpha 1-antitrypsin level can differentiate Weber-Christian disease from alpha 1-antitrypsin panniculitis.

• The absence of the characteristic clinical manifestations of systemic lupus erythematosis, normal erythrocyte sedimentation rate and C-reactive protein, negative anti-nuclear antibodies and anti double strand–DNA antibodies and normal C3 and C4 can differentiate Weber-Christian disease from lupus panniculitis.

• Biopsy of nodule demonstrated lobular panniculitis without vasculitis which differentiated Weber-Christian disease from panniculitis caused by vasculitis and thrombophlebitis.

• Normal immunoglobulin assay and Nitroblue Tetrazoluim test can differentiate Weber-Christian disease from immunodeficiency including chronic granulomatous disease.

• The diagnosis of Weber-Christian disease is a diagnosis of exclusion ⁴ with a lobular panniculitis without vasculitis in histopathology as demonstrated in our case.

Several treatment options were reported in the treatment of Weber-Christian disease. However, the best evidence exists for cyclosporine A and corticosteroids.^16–18 Cyclosporine A inhibits IL-2 production and transduction of antigen-recognition signals in activated T cells. Although the pathogenesis of Weber-Christian disease is not finally resolved, the response to cyclosporine A points towards a predominant involvement of T-cells in the disease process. ¹⁸

Our patient improved following corticosteroid treatment in dose of 2 mg/kg/day for 3 weeks and cyclosporine A (5 mg/kg/day) for 6 months with no activity reported and no appearance of any new swellings.

The prognosis Weber-Christian disease depends on which organs are affected, the severity of organ involvement, and the response to therapy. ² 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. ²