Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Abstract

For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant ‘autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice.

Our Autoimmune Hepatitis Patients: Single Center Experience

“…In a study conducted in Italy, the prevalence of non-liver autoimmune disease accompanying AIH was 42%, and autoimmune thyroiditis was common (31). In some studies, the rate of extrahepatic diseases was 29-38% (20,32). Studies have shown that patients with nonliver autoimmune disease do not differ in terms of disease progression and survival (31,33).…”

Sensory neuronopathy is a specific and disabling neurological manifestation of autoimmune hepatitis

“…Neurological manifestations have also been identified in the context of AIH [4][5][6][7][8]. Most reports described central nervous system diseases, particularly multiple sclerosis [9].…”

Adequacy of scoring systems in diagnosing paediatric autoimmune hepatitis: retrospective study using a control group children with Hepatitis B infection

“…In a small proportion of patients, antibodies are not detected and hence, AIH remains unclassified. In 20-50% of patients with AIH, other autoimmune disorders are associated (AAD), making the diagnosis even more difficult by overlapping symptoms while imprinting the prognosis by adding concurrent comorbidities that need extra-treatment (for example, gluten-free diet for coeliac disease, substitute hormones for autoimmune thyroiditis, step-up therapy for inflammatory bowel disease) (2,3). The mosaic of autoimmunity or shared autoimmunity is a concept described previously (4) and implies the existence of concurrent (even multiple) extrahepatic autoimmune disease in patients with AIH, the underlining mechanism not being yet fully described; therefore, screening of AAD in cases of AIH was proposed previously in adults studies and it was recently suggested by…”