Alpha-1 antitrypsin (AAT) deficiency and panniculitis

Author: M. Sandhu, M.D., Allergist/Immunologist, Vancouver, Canada
Reviewer: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago

A 22 year old female presented with a 3 week history of painful eruptions on the inner aspect of both thighs. Lesions were constant, worsening in nature over the past 3 weeks. Initially the diagnosis of cellulitis was entertained and the patient was placed on a 2 week course of oral antibiotics. Despite treatment with antibiotics the lesions did not improve.

Past medical history (PMH)

As above.



Family medical history

There was no family history of hepatic or pulmonary disease.

Physical examination

Skin: Lesions on inner aspect of both thighs, erythematous, indurated, nodular, warm and tender to palpation.
HEENT: normal. Eyes had no conjunctival injection or swelling, ears had no fluid or inflammation behind the TMs, nose had no mucosal edema or discharge.
Chest: CTA (B).
CVS: Clear S1S2.
Abdomen: Soft, NT, ND, +BS.
Extremities: no c/c/e.

What diagnostic tests would you suggest?

A biopsy was subsequently performed, which showed panniculitis. The patient was evaluated for possible causes of panniculitis including alpha-1 antitrypsin deficiency. Alpha-1 antitrypsin level was found to be less than 25mg/dl. Phenotyping analysis demonstrated a ZZ pattern. Pulmonary function testing was normal as was the CT scan of the chest. Liver function tests were also found to be normal except for a slightly elevated alkaline phosphatase.

What treatment would you suggest?

The patient was started on intravenous augmentation therapy with pooled plasma-derived alpha 1-antiprotease (Prolastin) at a dose of 60mg/kg weekly. The panniculitis had nearly completely resolved after the second dose.

Final diagnosis

Panniculitis in alpha-1 antitrypsin (AAT) deficiency.


Panniculitis is an uncommon manifestation of alpha-1 antitrypsin deficiency, with fewer than 50 cases reported in the English-language scientific literature. It is characterized by inflammation of the panniculus, which is the fibro-fatty tissue layer that lies below the superficial layers of the skin. The architecture resembles a honeycombing pattern, with globules of fat separated by walls (septae). Panniculitis is categorized as either being septal or lobular depending on whether if affects the septae or the fat globlules respectively. In AAT panniculitis, the mechanism resembles that of emphysema, namely the unopposed breakdown of tissue by the absence of alpha-1 antitrypsin, allowing proteases within the body to affect structures underlying the skin. Panniculitis typically presents with red nodular spots on the skin which may break down and ulcerate, causing an oily discharge. The lesions may progress to deep ulceration with necrosis. Common sites include the thighs and buttocks and areas subject to trauma. The presumed mechanism in our patient was from repeated trauma/friction during sexual intercourse.

Panniculitis can arise from many underlying causes. Potential causes include AAT deficiency, connective tissue disease such as Systemic Lupus Erythematosus and Scleroderma, lymphoproliferative disorders, pancreatic disease, gout, chronic kidney disease and adverse reactions to medications.

Various therapies have been evaluated to treat panniculitis, including corticosteroids, antibiotics (doxycycline and dapsone), full plasma exchange, and augmentation therapy with intravenous pooled human plasma alpha-1 antitrypsin. Of these various treatments, augmentation therapy has been the most dramatically successful. Several reports describe resolution of panniculitis after as few as three doses of intravenous augmentation therapy. The dose of augmentation therapy for panniculitis is the same as that for established emphysema, 60 mg/kg once weekly.

In summary, panniculitis can be a potentially disabling complication of AAT deficiency. Fortunately, it is an uncommon manifestation that is amenable to various treatment options, namely augmentation therapy. Since AAT deficiency is an under recognized syndrome, we should be aware of all its potential presentations, to aid in early diagnosis and subsequent treatment.

Importantly, panniculitis in Alpha-1 can accompany various phenotypes (or genetic types of Alpha-1 Antitrypsin Deficiency), some with severe deficiency of serum levels of alpha-1 antitrypsin (e.g., ZZ and SNull) and others with only mild deficiency (e.g., MZ and MS). In one series by Humbert and colleagues, of the 26 patients with panniculitis and Alpha-1 Antitrypsin Deficiency described, 62% were ZZ, 15% were MZ, 8% were MS, and 4% were SNull; in the remaining 8%, the phenotype was not stated. The reported experience suggests that panniculitis occurs equally among men and women and that the mean age of onset is approximately 40 years old.

Related reading

Therapy with alpha-1 antitrypsin cannot be recommended, in view of the lack of evidence of clinical benefit and the high cost of treatment. The Cochrane Collaboration, 2010.

A 2012 Review of Alpha 1-Antitrypsin Deficiency - from Cleveland Clinic

Published: 03/19/2010
Updated: 01/19/2012

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