Panniculitis alpha-1-antitrypsin deficiency associated M35.6

Very rare (about 60 cases have been described so far), clinically difficult (lethal outcome possible), very painful, often recurrent, nodular and necrotizing panniculitis syndrome, which is due to a congenital alpha-1-antitrypsin deficiency.

Mostly hereditary (autosomal recessive inheritance; chromosome 14q32.1 associated; protein polymorphism). Alpha-1-antitrypsin is a protease inhibitor, especially for neutrophil elastase and also performs important anti-inflammatory functions(acute phase protein).

Predominantly located on the extensor sides of the extremities, buttocks, trunk.

Single or disseminated, painful, indurated, subcutaneous fat tissue nodes with a tendency to ulceration(lobular neutrophilic panniculitis). Frequently spontaneous emptying of the nodules with secretion of oily, bloody, tinged fluid.

The main clinical and dermatological symptoms are: haemorrhagic nodules and tolerated deep ulcers of the lower legs.

Not infrequently arthralgias and fever. Common accompanying symptoms:

• Icterus prolongatus of the newborn
• Hepatitis of unknown origin in infancy or childhood
• Pulmonary emphysema in adults (reduction of elastin in the lung skeleton due to unhindered elastase activities)
• Hepatitis or cirrhosis of the liver of unknown origin in adults (probably accumulation of structurally altered, defective alpha-1-antitrypsin in the hepatocytes.

Alcohol and nicotine withdrawal!

Initially, or for less severe courses, dapsone (e.g. sulfone tablets) 50-150 mg/day p.o. can be tried.

Substitution of α-1-antitrypsin (e.g. Prolastin HS) with at least 60 mg/week to maintain the minimum reference value in the blood.

• 21-year-old patient with painful, reddened lumps on the proximal extremities and on the back that have been present for one month. Known AAT deficiency since the neonatal period in Z.n. neonatal hepatitis.
• Findings: Ulcerated nodules in the area of the right hip and left shoulder with discharge of yellowish oily fluid. In the further course of the disease corresponding lesions at a different localization with inhomogeneous pigmented healing.
• Laboratory: Serum AT concentration at presentation: 0.3 g/l (normal 0.9-2.0 g/l); phenotype Pi ZZ. All other values (incl. Diff. BB, CRP, ANA, c-ANCA, p-ANCA, anti-PR3 and anti-MPO) in the normal range.
• Bacteriology: No detection of aerobic or anaerobic germs.
• X-ray thorax: Unobtrusive.
• Histology: Septal panniculitis with strong infiltration of polymorphonuclear leukocytes.
• Therapy: Initial prednisolone 50 mg/day p.o. for several days, no improvement of findings, then gradual reduction. Supplementation with dapsone 100 mg/day p.o. with dose adaptation to 150 mg/day in case of therapy failure. After 3 months no improvement in findings. Switch to alpha-1-protease inhibitor with weekly intravenous administration of 60 mg/kg bw. The lesions heal within 2 days after initial administration. After 8 weeks, first therapy break with administration of alpha-1-protease inhibitor only if the changes recur (initially after 2-4 weeks, later after 6 weeks).

1. Blanco I et al (2015) Neutrophilic Panniculitis Associated with Alpha-1 Antitrypsin Deficiency: an Update. Br J Dermatol doi: 10.1111/bjd.14309
2. Chowdhury MM et al (2002) Severe panniculitis caused by homozygous ZZ alpha1-antitrypsin deficiency treated successfully with human purified enzymes (Prolastin). Br J Dermatol 147: 1258-1261
3. Laureano A et al (2014) Alpha-1-antitrypsin deficiency-associated panniculitis: a case report. Dermatol Online J 20: 2124
4. Requena L et al (2001) Panniculitis. Part II. Mostly lobular panniculitis. J Am Acad Dermatol 45: 325-361
5. Ural I et al (2002) Nodular vasculitis associated with chronic hepatitis C. J Eur Acad Dermatol Venereol 16: 298-289
6. Vigl K (2015) Alpha-1-antitrypsin deficiency, Pyoderma gangraenosum-like necrotising panniculitis: lethal course. JDDG 13: 1180-1182
7. Warter J et al (1972) Syndrome de Weber-Christian associe a un deficit en alpha-1-antitrypsine; enquete familiale. Ann Med Interne (Paris) 123: 877-882