The following article is a reprint from the Alpha-1 Foundation Research Registry Update Spring/Summer Issue 2007 and represents the most comprehensive information on Alpha-1 associated Panniculitis.
Panniculitis in Alpha-1 Antitrypsin Deficiency
Panniculitis is an uncommon manifestation of alpha-1 antitrypsin deficiency. This brief paper will discuss the definition of panniculitis, the variety of potential causes, current understanding of the mechanism of panniculitis, its signs and symptoms, and available experience with treatment.
Panniculitis is an inflammation of the panniculus, which is the fibro-fatty tissue layer that lies underneath the outermost or superficial layers of our skin. This layer of the skin resembles a honeycomb, with globules of fat separated by walls, or septae. In anatomic terms, panniculitis is categorized as either being septal (involving the walls separating the fatty sections of the panniculus) or lobular (affecting the fat globules or collections themselves).
Like most medical conditions, panniculitis can arise from many underlying causes. Alpha-1 Antitrypsin Deficiency is one of those causes. Among the other potential causes are a group of diseases known as connective tissue disease (which include conditions causing diffuse body inflammation, such as systemic lupus erythematosus and rheumatoid arthritis), underlying so-called lymphoproliferative diseases (like lymphoma), pancreatic disease, gout, kidney dysfunction, so-called atheroembolism (in which clots from blood vessels find their way to the fibro-fatty layer of the skin), and even adverse reactions to some drugs, including corticosteroids.
Panniculitis manifests as characteristically red nodular spots on the skin which may break down and ulcerate, causing an oily discharge. While these nodular blotches may occur anywhere on the body, common sites include the thighs and buttocks and areas subject to trauma.
Conditions that may precipitate the development of such nodules include trauma (including rigorous exercise), intravenous injections, cryosurgery on the skin (which is surgery involving freezing the skin). The lesions of panniculitis may go on to develop deep ulceration with tissue breakdown, called necrosis. Such necrotic nodules are usually painful to the touch.
Panniculitis is felt to be due to inflammation of the fibro-fatty layer of the skin, presumably mediated by unopposed protein breakdown. In Alpha-1-related panniculitis, the mechanism of panniculitis resembles that believed to cause the development 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 (in the case of panniculitis) or the support matrix of the lung (in the case of emphysema).
Panniculitis is an uncommon complication of Alpha-1 Antitrypsin Deficiency. It was first described in a patient in France in 1972 by Dr. Warter and colleagues. These physicians described a young woman with severe deficiency of alpha-1 antitrypsin who developed characteristic red nodular, painful skin ulcers. Since that original report, fewer than 50 cases of panniculitis in individuals with Alpha-1 Antitrypsin Deficiency have been reported in the medical literature, establishing that panniculitis is a very uncommon complication of Alpha-1 Antitrypsin Deficiency. For example, in the National Heart, Lung, and Blood Institute Registry of Individuals with Severe Deficiency of Alpha-1 Antitrypsin, only a single participant reported having panniculitis. In various reports specifically about panniculitis and Alpha-1, only 28 patients had been described through 1997. Tallying all reported cases through 2003 shows a total of 44 individuals with panniculitis complicating Alpha-1 Antitrypsin Deficiency described in the medical literature.
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., including PI*ZZ and PI*SNull) and others with only mild deficiency (e.g., PI*MZ and PI*MS). In one series by Humbert and colleagues, of the 26 patients with panniculitis and Alpha-1 Antitrypsin Deficiency described, 62% were PI*ZZ, 15% were PI*MZ, 8% were PI*MS, and 4% were PI*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.
Various therapies have been tried and evaluated to treat panniculitis, including corticosteroids, antibiotics (including doxycycline and dapsone), full plasma exchange, and intravenous pooled human plasma alpha-1 antitrypsin (more popularly called augmentation therapy). 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 both an annoying and also potentially disabling complication of Alpha-1 Antitrypsin Deficiency. Panniculitis is thankfully very uncommon and is amenable to effective treatment with existing approaches for Alpha-1, including augmentation therapy. Undoubtedly, the spectrum of treatment choices for panniculitis will grow along with ongoing research regarding optimal therapy of individuals with Alpha-1 Antitrypsin Deficiency and with the development of new treatment options.