Alpha-1 antitrypsin deficiency panniculitis

Introduction

Nodular panniculitis refers to inflammatory nodules in the subcutaneous fat. Nodules may be, single or multiple, localezed or generalized, and vary in size from a few milimeters to several centimeters in diameters. They are generally firm, red and tenderm but occasionally they become soft and may liquefy, or even ulcerate. They may resolve with or without scarring.[1] The definitive diagnosis is often difficult, since there are many causes and in many patients the caused cannot be found.[2] However, in some cases, there may be an underlying cause such as proteinase inhibitor deficiency. Herein a case of alpha-1 antitrypsin deficiency leading to panniculitis is described.

Case Report

A 48-year-old housewife complained of recurrent painful nodular eruptions on the abdomen of 8 months duration. Onset was insidious and gradual with a few papulonodular lesions appearing on the periumbilical area, which gradually became enlarged and tender. On several occasions the area around the umbilicus used to become reddish and warm, associated with increase in pain and low grade fever. After about a week there was spontaneous rupture of the nodules with discharge of an oily fluid, following which the redness and the pain used to subside partially. This cycle was repeated often during the preceding 8 months. The eruptions were localized only to the abdomen. She denied any history of similar eruptions over the legs or upper limbs. There was no family history of similar complaints. The patient had undergone laparoscopic cholecystectomy for gall bladder calculi a year ago. There was no antecedent history of hepatitis, pancretitis, cirrhosis, pleural effusion, or emphysema in the past. She denied history of taking any drugs for any chronic illnesses in the past.

Dermatological examination showed multiple erythematous nodular lesions on the periumbilical area with surrounding brawny warm induration of the subcutaneous fat. The entire are a was on palpation. Some of the erstwhile lesions had resolved leaving post inflammatory pigmentation. A few of the subcutaneous nodules had coalesced to form plaques. Some areas of the fluctuation were present from which a few nodules had ruptured to exude an oily [Figure - 1]. No discharge of pus, serosanguinous fluid or grains was noticed. There were no similar lesions anywhere else on the body. Systemic examination did not reveal any abnormality in the lungs, or abdomen.

Investigations revealed normal hematological and biochemical reports. Pancreatic function was normal as revealed by normal serum amylase. The oily fluid revealed lipid droplets under microscopy and stained orange red with Sudan red. An estimation of alpha-1 antitrypsin level in the blood revealed a level of 50mg/dl, as against a normal range of 93-224 mg/dl. Enzyme genotyping was however not done due to lack of appropriate facilities. A biopsy deep enough to include the subcutaneous tissue revealed splaying of neutrophils between collagen bundles in the reticular dermis in few areas, while other areas showed oedema and fragmentation of the dermal collagen and intense infiltration by neutrophils, lymphocytes and few macrophages around mature adipocytes in the subcutis. Some areas of elastolysis was also present. An area of necrotic ulceration was seen around which there were essentially normal adipocytes.

The features were tenable with a diagnosis of alpha-1 antitrypsin panniculitis and the patient was treated with dapsone 100 to 200 mg daily with partial relief in the inflammatory condition.

Discussion

Alpja-1 antitrypsin is the principal serum protease inhibitor. Severe deficiency of this important inhibitor is inherited as the ZZ phenotype, which occurs in about 1 in 2500 people.[3] In addition to the well-recongnized association with early-onset emphysema and cirrhosis, alpha 1 -antitrypsin deficiency may be associated with panniculitis. Most of the cases with manifestations of cirrhosis and empysema have the severe type of deficiency (ZZ phenotype), whereas the partial deficiency (MZ phenotype) with less severe symptoms confined to cutaneous lesions, is more common. There are five possible mechanisms outlined for the pathogenesis of panniculitis due to the deficiency of alpha-1 antitrypsin.[4] Trauma is known to precipitate panniculitis in an individual with an inhibitor deficiency. In this case too, trauma during laproscopic pall bladder surgery in the periumbilical area could have precipitated the panniculitis.

An early histopathological clue to the diagnosis of alpha-1 antitrypsin panniculitis is the splaying of neutrophils between collagen bundles in the reticular dermis.[5] In the present case too, in areas of early involvement, the same histopathological finding was present. Differentiating histopathological features, from other forms of panniculitis, are presence of large areas of normal fat adjacent to necrotic lobular and septa) areas, that contain intense polymorphonuclear and macrophage infiltration. Elastolysis is also characteristic of alpha-1 antitrypsin panniculitis.[6] These two features were also present in the case illustrated.

This case highlights the importance of testing for serum levels of alpha-1 antitrypsin in case of panniculitis, especially if the condition is chronic and indolent with spontaneous areas of ulceration and drainage of oily yellow fluid. Dapsone works effectively in most cases, as in the-present case. Severe cases with life threatening complications like cirrhosis, emphysema and pleural effusions may require, in addition, oral steroids and alpha-1 proteinase inhibitor infusions.[4] No conclusion can be drawn, to recommend preoperative screening for alpha-1 antitrypsin deficiency in patients undergoing any abdominal surgery, laparoscopic or otherwise, based on this case. This will require establishing a more direct evidence of surgical trauma in precipitating alpha--1 antitrypsin panniculitis.