A CASE OF SYSTEMIC NODULAR PANNICULITIS ASSOCIATED WITH M1 (VAL213) Z-PHENOTYPE OF ALPHA(1)-PROTEASE INHIBITOR

A 31-year-old woman presented with a 13-year history of tender, subcut aneous nodules on her arms, abdomen, buttocks, back, and thighs. In th e most acute phase the inflammation of the subcutaneous tissue was mor e diffuse. Subsequently the nodules ulcerated and discharged an oily f luid. The course fluctuated, with periods of intense inflammation at s everal fatty sites and times of low-grade inflammation. Systemic sympt oms included Raynaud's phenomenon, joint pains involving her hands, el bows, and shoulder, and morning stiffness lasting about 1-2 h. The pat ient was never completely free of disease in spite of almost continuou s treatment, including chloroquine for 3 months which was stopped foll owing visual problems, potassium iodide which caused asphyxic reaction and was stopped, pulse therapy with cyclophosphamide which was associ ated 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 min imal 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 sc ars on her arms and buttocks. Some discharging sinuses with adjacent a reas of inflammation were present on the buttocks.Re-examination of bi opsies taken 10 years previously and diagnosed as indicative of Weber- Christian disease showed subcutaneous fat necrosis with dystrophic cal cification. An inflammatory infiltrate consisting of polymorphonuclear leukocytes, lymphocytes, macrophages, and foam cells surrounded the n ecrotic tissue. Some of the lesions formed sinuses lined by granulatio n tissue extending from the subcutaneous necrotic tissue to the surfac e of the skin. The full blood count was normal, as were the sedimentat ion rate, electrolytes, and amylase. The liver function tests demonstr ated a raised Gamma-glutamyl transferase (GGT), but were otherwise nor mal. The anti-nuclear factor (ANF) was positive, with a titre for anti centromere antibodies of > 1/640. Anti-ds-DNA and rheumatoid factor we re negative. The phenotype (Pi) and genotype of alpha(1)-protease inhi bitor (alpha(1)-PI) was determined in the patient and her family. This was performed as previously described.(1) The phenotype of the patien t's mother and all her siblings was found to be (Pi) M1 (Val213)Z, whi le her father was (Pi) M1(Val213)M1(Val213) (Table 1). Concentrations of alpha(1)-PI were somewhat below the normal range (2-4 g/L) in the p atient and other family members with a similar phenotype, but so too w as the concentration in the unaffected father. In addition, there was a modest but significant reduction in plasma elastase inhibitory capac ity (EIC) in subjects with the Pi M1(Val213)Z phenotype.