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

Porphyria cutanea tarda (PCT) is the most common type of porphyria. The accumulation of porphyrin in various organ systems results from a deficiency of uroporphyrinogen decarboxylase (UROD).^1-3 Chronic hepatitis C virus (HCV) causes a hepatic decrease in hepcidin production, resulting in increased iron absorption. Iron loading and increased oxidative stress in the liver leads to nonporphyrin inhibition of UROD production and to oxidation of porphyrinogens to porphyrins.⁴ This in turn leads to accumulation of uroporphyrins and carboxylated metabolites that can be detected in urine.⁴

Signs of PCT include blisters, vesicles, and possibly milia developing on sun-exposed areas of the skin, such as the face, forearms, and dorsal hands.⁴ Case reports have demonstrated a resolution of PCT in patients with chronic HCV with treatment with direct-acting antivirals (DAAs), such as ledipasvir/sofosbuvir.^1,3 However, here we present 2 cases of patients who developed blistering diseases during treatment of chronic HCV with ledipasvir/sofosbuvir. Neither demonstrated complete resolution of symptoms during the treatment regimen.

Cases

Patient 1

A 63-year-old white male with a history of chronic HCV (genotype 1a), bipolar disorder, hyperlipidemia, tobacco dependence, and cirrhosis (F4 by elastography) presented with minimally to moderately painful blisters on his bilateral dorsal hands that had developed around weeks 8 to 9 of treatment with ledipasvir/sofosbuvir. The patient reported that no new blisters had appeared following completion of 12 weeks of treatment and that his current blisters were in various stages of healing. He reported alcohol use of 1 to 2 twelve-ounce beers daily and no history of dioxin exposure. His medications included doxepin, hydralazine, hydrochlorothiazide, quetiapine, folic acid, and thiamine. His hepatitis C viral load was 440,000 IU/mL prior to treatment. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron level was 135 µg/dL, total iron-binding capacity (TIBC) was 323 µg/dL, and ferritin was 299.0 ng/mL. His HFEgene was negative for mutations. Following 4 weeks of treatment with ledipasvir/sofosbuvir, a hepatitis C viral load was not detected.

A physical examination on presentation revealed erosions with overlying hemorrhagic crusts on the bilateral dorsal hands (Figure).

At the 4-month follow-up, the patient reported no new blister formations. A physical examination revealed well-healed scars and several clustered milia on bilateral dorsal hands with no active vesicles or bullae noted.

Patient 2

An African American male aged 63 years presented with a 1-month history of moderately painful blisters on his bilateral dorsal hands during treatment of chronic HCV (genotype 1a) with ledipasvir/sofosbuvir. His medical history included gout, tobacco and alcohol addiction, osteoarthritis, and hepatic fibrosis (F3 by elastography). The patient’s medications included allopurinol, lisinopril, and hydrochlorothiazide. He reported no history of dioxin exposure. On the day of presentation, he was on week 9 of the 12-week treatment ledipasvir/sofosbuvir regimen. Laboratory results included an initial HCV viral load of 1,618,605 IU/mL. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron was 191 µg/dL, TIBC 388 µg/dL, and ferritin 459.0 ng/mL. After 4 weeks of treatment, the patient’s hepatitis C viral load was undetectable.