A case of systemic nodular panniculitis associated with M1 (Val213) Z phenotype of α1‐protease inhibitor

A 31‐year‐old woman presented with a 13‐year history of tender, subcutaneous nodules on her arms, abdomen, buttocks, back, and thighs. In the most acute phase the inflammation of the subcutaneous tissue was more diffuse. Subsequently the nodules ulcerated and discharged an oily fluid. The course fluctuated, with periods of intense inflammation at several fatty sites and times of low‐grade inflammation. Systemic symptoms included Raynaud's phenomenon, joint pains involving her hands, elbows, and shoulder, and morning stiffness lasting about 1–2 h. The patient was never completely free of disease in spite of almost continuous treatment, including chloroquine for 3 months which was stopped following visual problems, potassium iodide which caused asphyxic reaction and was stopped, pulse therapy with cyclophosphamide which was associated with some improvement, dapsone for 3 months which had no effect, and prednisone (up to 90 mg/day) for a few weeks which resulted in minimal improvement. The patient had previously been treated for urinary tract infections and had been investigated for primary infertility. At the time of the present examination, there were multiple depressed scars on her arms and buttocks. Some discharging sinuses with adjacent areas of inflammation were present on the buttocks. Re‐examination of biopsies taken 10 years previously and diagnosed as indicative of Weber‐Christian disease showed subcutaneous fat necrosis with dystrophic calcification. An inflammatory infiltrate consisting of polymorphonuclear leukocytes, lymphocytes, macrophages, and foam cells surrounded the necrotic tissue. Some of the lesions formed sinuses lined by granulation tissue extending from the subcutaneous necrotic tissue to the surface of the skin. The full blood count was normal, as were the sedimentation rate, electrolytes, and amylase. The liver function tests demonstrated a raised Gamma‐glutamyl transferase (GGT), but were otherwise normal. The anti‐nuclear factor (ANF) was positive, with a titre for anticentromere antibodies of > 1/640. Anti‐ds‐DNA and rheumatoid factor were negative. The phenotype (Pi) and genotype of α 1 ‐protease inhibitor (α 1 ‐PI) was determined in the patient and her family. This was performed as previously described. 1 The phenotype of the patient's mother and all her siblings was found to be (Pi) Ml (Val213)Z, while her father was (Pi) M1(Val213)M1(Val213) (Table 1). Concentrations of α 1 ‐PI were somewhat below the normal range (2–4 g/L) in the patient and other family members with a similar phenotype, but so too was the concentration in the unaffected father. In addition, there was a modest but significant reduction in plasma elastase inhibitory capacity (EIC) in subjects with the Pi M1(Val213)Z phenotype.