Skin Manifestations Associated with Autoimmune Liver Diseases: a Systematic Review

Abstract

Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often associated with extrahepatic autoimmune diseases. However, the association with cutaneous diseases is less well described. In the present article, we provide a systematic literature review on skin manifestations linked to each of these four autoimmune liver diseases, excluding skin manifestations of systemic diseases. The association of autoimmune hepatitis with vitiligo is well known, with a particular striking association with type 2 autoimmune hepatitis, a condition occurring almost entirely in children and adolescents, much rarer and more aggressive than type 1 autoimmune hepatitis; probable associations are also identified with alopecia areata, psoriasis, and pyoderma gangrenosum. Primary biliary cholangitis is not linked to lichen planus as previously assumed, but to vitiligo, psoriasis and the very rare amicrobial pustulosis of the folds. The proposed diagnostic criteria for this latter condition include the presence of anti-mitochondrial autoantibodies, the serological hallmark of primary biliary cholangitis. The very strong association of primary sclerosing cholangitis with inflammatory bowel diseases hampers the search for an association with skin diseases, since inflammatory bowel diseases have a strong association with various dermatological condition, including neutrophilic dermatoses and erythema nodosum. Nevertheless, a probable association of primary sclerosing cholangitis with psoriasis is identified in this review. Variant syndromes, also called overlap syndromes, are likely associated with vitiligo as well, which is not surprising, since autoimmune hepatitis is a feature of these conditions and they may share regions of the MHC.

Gastrointestinal involvement of primary skin diseases

“…Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis, are often associated with extrahepatic autoimmune manifestations. 97,98 The association of autoimmune hepatitis with vitiligo is well known, 99 while the presence of autoimmune thyroid diseases seems to play a role. Associations with alopecia areata, psoriasis and pyoderma gangrenosum have also been described.…”

“…97,98 In addition to pruritus, butterfly sign on the upper back, xanthomatoses and skin hyperpigmentation, a possible association with vitiligo, psoriasis and amicrobial pustulosis of the folds remains to be confirmed. 98 Primary sclerosing cholangitis is a rare chronic progressive inflammation and fibrosis of medium to large intra-and extrahepatic bile ducts, affecting more men than women in the middle ages. 97,98 Due to a strong association with inflammatory bowel disease, the attribution of the concurrence with pyoderma gangrenosum, erythema nodosum and psoriasis is difficult to determine.…”

“…98 Primary sclerosing cholangitis is a rare chronic progressive inflammation and fibrosis of medium to large intra-and extrahepatic bile ducts, affecting more men than women in the middle ages. 97,98 Due to a strong association with inflammatory bowel disease, the attribution of the concurrence with pyoderma gangrenosum, erythema nodosum and psoriasis is difficult to determine. 98 Further studies are required to understand the associations between vitiligo and autoimmune atrophic gastritis or coeliac disease in terms of autoimmune pathogenesis.…”

Unmet needs in autoimmune liver diseases

“…Autoimmune liver diseases consist of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis, juvenile autoimmune hepatitis and variant syndromes . Although a growing body of evidence indicates that individuals with particular genetic backgrounds may develop autoimmune liver diseases with accumulating environmental triggers, the pathogenesis behind these conditions is still incompletely elucidated .…”

The challenges of primary biliary cholangitis: What is new and what needs to be done

“…Autoimmune liver serology, which would be very helpful in the characterization of patients, is hampered by insufficiently standardized methods of testing. It should be emphasized that in PBC there is an increased prevalence also of extrahepatic autoimmune manifestations including scleroderma, sicca syndrome and related rheumatic diseases(247).…”