In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.
Alpha-1 antitrypsin deficiency – Genetics Home Reference
Panniculitis – Alpha-1 Foundation
Panniculitis is an inflammation of the panniculus, the layer of fatty and fibrous tissue just beneath the outer layers of our skin. This layer of the skin looks like a honeycomb, with globules of fat separated by walls, or septae.
Like most medical conditions, panniculitis can have many underlying causes. Alpha-1 Antitrypsin Deficiency (Alpha-1) is one of those causes. There are many other causes, including diseases that involve widespread inflammation of the body such as lupus (systemic lupus erythematosus) and rheumatoid arthritis, and reactions to some drugs, including corticosteroids.
What panniculitis looks like
Panniculitis typically appears as raised red spots on the skin, which may break down and give off an oily discharge. While panniculitis spots (called nodules) may appear anywhere on the body, the most common places are the thighs, buttocks, and areas subject to injury or pressure.
Panniculitis nodules sometimes appear after some injury. This includes injuries that would be minor in most people – vigorous exercise, intravenous injections, and cryosurgery (surgery involving freezing the skin).
Panniculitis spots may develop into deep ulcers in the skin, with tissue breakdown, called necrosis. Such spots are usually painful to the touch. The medical term for this is “necrotizing panniculitis.”
Panniculitis can be annoying and painful, even disabling. Fortunately, it is the rarest of the well-known complications of Alpha-1 Antitrypsin Deficiency.
In Alphas (people with Alpha-1), the inflammation and development of panniculitis has a clear similarity to the development of emphysemaObstructive airway disease in which the walls of the alveoli (air sacs) are damaged or destroyed.:
In both the skin and the lungs of Alphas, there is a lack of alpha-1 antitrypsin (AATalpha-1 antitrypsin), which normally balances the action of proteases – enzymes that break down proteins as part of normal body functioning. When the alpha-1 protein is missing or abnormal and not functioning, this balance breaks down. Proteases within the body can then damage the structures underlying the skin (in panniculitis) or the support matrix of the lung (in emphysemaObstructive airway disease in which the walls of the alveoli (air sacs) are damaged or destroyed.).
Panniculitis due to Alpha-1 was first described by physicians in France in 1972. They described a young woman with severe Alpha-1 who developed the characteristic red nodules and painful skin ulcers.
Panniculitis is defined as inflammation of the subcutis. Alpha-1 antitrypsin deficiency (AATD) is clearly, although uncommonly, associated with panniculitis. Clinical manifestations of panniculitis associated with AATD include red, painful nodular lesions that often weep with an oily discharge and commonly occur on the thighs, buttocks, and areas of physical trauma. Some distinctive clinical features of the panniculitis associated with AATD include neutrophilic inflammation, mainly lobular involvement, and frequent ulceration with oily drainage. The pathophysiology of panniculitis in AATD presumably relates to unopposed elastase activity.
Clinical experience with panniculitis in AATD is limited. Since the first reported case in 1972 in a young woman, literature review indicates that through 2004, a total of 41 patients had been reported. A MEDLINE search to the present time indicates 3 additional patients reported, for a total of 44 reported individuals. With regard to prevalence, only 1 of the 1129 participants in the National Heart, Lung, and Blood Institute Registry reported panniculitis. Among patients with panniculitis, available series suggest that PI*SS or PI*ZZ individuals comprise up to 5% of the group.
Various therapies for panniculitis associated with AATD have been tried, including corticosteroids, doxycycline, dapsone, plasma exchange, liver transplantation, and intravenous pooled human plasma alpha-1 antiprotease. Although neither a systematic comparison of available treatments or even a large observational series with any one therapy is available, the small reported experience with augmentation therapy suggests that this can confer rapid and dramatic improvements in panniculitis in alpha-1 antitrypsin deficient individuals.
Panniculitis in Alpha-1 Antitrypsin Deficiency: A Review – Clinical PulmonaryMedical term referring to the lungs. Medicine
Ten patients with AATD panniculitis were included. Seven of ten were women. Clinical lesions were most commonly nodular (100%), erythematous (90%), ulcerated (90%), and painful (90%) subcutaneous nodules and plaques. Extracutaneous associations were rare. PiZZ phenotype was most commonly identified (50%).
Alpha-1 antitrypsin deficiency panniculitis: clinical and pathologic characteristics of 10 cases – NCBI
Panniculitis caused by homozygosity of ZZ alpha 1-antitrypsin (A1AT) deficiency is extremely rare despite the relatively common presence of ZZ phenotype affecting approximately 1 in 3500 people among whites in Western Europe…
Severe ulcerative panniculitis caused by alpha 1-antitrypsin deficiency: Remission induced and maintained with intravenous alpha 1-antitrypsin – Journal of American Academy of DermatologyA1AT is a potent serine protease inhibitor synthesized in the liver and acts through regulation of proteolytic enzymes which include trypsin, elastase, factor VIII, chymotrypsin, collagenase, and kallikrein. Its deficiency therefore results in the inadequate inhibition of proteases released by neutrophils and monocytes, leading to inflammation and tissue necrosis. Panniculitis is such an inflammation and may be the first sign of the disease. It is characterized histologically by an intense neutrophilic infiltration in the fat lobules, often associated with collagenolysis and degeneration of elastic tissue and septa leading to the classic “oily discharge” from the ulcerated areas representing necrotic adipocytes, often resolving with atrophic scarring. Another characteristic feature is the presence of normal fat tissue adjacent to necrotic and inflamed adipocytes. Vasculitis is typically absent. Trauma has been known to trigger panniculitis in patients with A1AT deficiency, possibly because of the rise of protease activation triggering a cascade of inflammatory events. The rarity of panniculitis in relation to the A1AT deficiency prevalence suggests that triggering factors like trauma and infections must be present in order to initiate an inflammatory cascade resulting in tissue damage when A1AT levels are deficient.