Blistering Disease During the Treatment of Chronic Hepatitis C With Ledipasvir/Sofosbuvir

A physical examination revealed several resolving erosions to his bilateral dorsal hands, some of which had overlying crusting along with one small hemorrhagic vesicle on the right dorsal hand. A punch biopsy of the hemorrhagic vesicle was performed and demonstrated a cell-poor subepidermal blister with festooning of the dermal papilla. A direct immunofluorescence study showed immunoglobulin (Ig) G fluorescence along the dermal-epidermal junction and within vessel walls in the superficial dermis. Weak IgM and C3 fluorescence also was noted within vessel walls in the superficial dermis. All of the patient findings and history were consistent with PCT, although pseudo-PCT also was a consideration. A 24-hour urine sample yielded negative results for porphobilinogen. Urine porphyrin test results were not available, leading to a presumptive histological diagnosis of PCT.

The patient completed 11 of the prescribed 12 weeks of ledipasvir/sofosbuvir. The blisters resolved shortly thereafter.

Discussion

PCT has a well-established association with chronic HCV infection.⁴ We present 2 cases of a blistering disease clinically and histologically compatible with PCT that developed in patients only after initiation of treatment for chronic HCV with ledipasvir/sofosbuvir. One case was confirmed as PCT on the basis of compatible histopathologic findings and a urine porphyrin assay that showed elevated levels of uroporphyrins and carboxylated metabolites. The second case was clinically and histologically suggestive of PCT but not confirmed by urine porphyrin testing. In both patients, after 8 to 9 weeks of a 12-week course of antiviral therapy, the blistering lesions were noted but appeared to be resolving, and no new lesions were noted after discontinuation of therapy. It appeared that the antiviral treatment temporally triggered the initiation of the blistering skin disease, and as the chronic HCV infection cleared after treatment, the blistering lesions also began to resolve.

Mechanistically, it is known that the virally-induced hepatic damage leads to inhibition of uroporphyrinogen decarboxylase, and the subsequent oxidation of porphyrinogens to porphyrins. Cofactors such as HIV infection also may contribute to development of PCT.⁵

De novo PCT has been documented during therapy using interferon and ribavirin.⁶ The hemolytic anemia and increased hepatic iron were implicated as potential etiologies.⁶ Patients with HCV and PCT treated with the newer direct-acting antiviral therapies have been described to have experienced improvement in PCT symptoms.³

Although there were rare reports of deterioration in renal and liver function,⁷ reactivation of HBV infection,⁸ and Stevens-Johnson syndrome⁹ with antiviral therapy, these complications were not observed in these patients. Both patients also had successful resolution of HCV infection, and by completion of the antiviral therapy, the blistering also resolved.

Conclusion

PCT is an extrahepatic manifestation of HCV infection. Health care providers should be aware of the association of chronic HCV infection with PCT. The findings of PCT should not result in the delay or discontinuation of antiviral therapy.