The incidence and prevalence of uveitis differ based on age, anatomic position of the inflammatory process (anterior, intermediate, posterior uveitis, pan-uveitis), gender, histopathology (granulomatous, non-granulomatous), course of an inflammatory process (acute, chronic, recurrent), and etiology (infectious, non-infectious). In the most parts of the world, the most common anatomic form is anterior uveitis.(1, 2) According to the etiology, infectious causes are common in the developing countries, and non-infectious etiologies are generally more frequent in the developed world.(6) the most common causes of infectious uveitis varies according to geographical locations.(7) The clinical and etiologic patterns of uveitis in Northeastern Iran was evaluated by Hosseini et al. They showed pan-uveitis was the most common clinical pattern, most of which were idiopathic, and toxoplasmosis was the most common infectious cause of uveitis.(8) Hepatitis viruses are among the infective agents that have been considered in the pathogenesis of uveitis. The association between viral hepatitis and uveitis has been proposed in few studies, most of which being about the role of hepatitis B and C in the pathogenesis of uveitis. These studies noticed that deposition of circulating immune complexes might leading to non-hepatic manifestations such as glomerulonephritis, and polyarteritis nodosa.(3, 4) The extra-hepatic manifestations which have been reported associated with HAV infection include glomerulonephritis, acute renal failure (ARF), myositis, acute pancreatitis, arthritis, pleural or pericardial effusion, myocarditis, autoimmune thrombocytopenic purpura, erythematous maculopapular rash, and parotitis. In these conditions, depositions of immune-complex in the various organs such as skin, joint, kidney, and muscle leading to immune system activation.(5, 9–11) Also Bhatt at el. noted that in addition to immune-related mechanisms, direct invasion of HAV into the kidney tissues might lead to ARF.(10) In the review of literature, ophthalmic manifestations associated with HAV infection not have been reported yet. Stangos et al, reported a case of multiple evanescent white dot syndrome (an inflammatory retinal disorder) 10 days after receiving simultaneous formalin-inactivated HAV and live-attenuated yellow fever vaccine. They concluded an autoimmune mechanism resulting this ocular inflammation.(12) The uvea is rich in blood vessels, so antigen-antibody complex deposition in the vascular network of uvea and choroid may lead to activation of the immune system. Also, expression of pro-inflammatory cytokine e.g. interleukin 1, and human leukocyte antigens e.g. HLA-DR in the intraocular tissues secondary to systemic viral infection or inflammation may resulting in uveitis.(13–15) However, the primary immune-related mechanisms that compromise the intraocular immune privilege and blood–ocular barrier are not known.(14, 15) In most previous reports, the extra-hepatic manifestations of HAV infection were occurred following initial non-specific symptoms.(5, 9, 11) In our case, acute anterior uveitis as an extra-hepatic manifestation of HAV infection was diagnosed 3 days before presentation of hepatic symptoms. Also Bhatt at el. reported a 34 year-old man with acute parotitis and facial skin rash as presented manifestations of HAV infection was diagnosed 6 days before hepatic presentations.(10) It seems, extra-hepatic manifestations of HAV infection may occur before (at the incubation period) or after presentation of hepatic signs secondary to deposition of circulating immune-complex in the various organs.
To the best of our knowledge, our case is the first report of anterior granulomatous uveitis associated with HAV infection. The pathophysiology of the ocular involvement of HAV infection is unknown. As mentioned earlier, the possible mechanism for ocular involvement might be immune-related such as antigen-antibody complex and activation of complement pathway. Therefore, administration of topical steroid and other anti-inflammatory drops can be helpful to control the ocular inflammation in this condition. We used topical prednisolone 1% to manage the inflammatory process as well as topical cycloplegic drop to relieve the pain and prevent synechia formation. We did not perform anterior chamber sampling, although it might help in detection of direct HAV-induce uveitis or immune-related uveitis. (15) We suggest patients with acute anterior uveitis, and a history of contact with contaminated water that live in or come from endemic areas for HAV should have this disease included in their differential diagnosis.