Resolution of Porphyria Cutanea Tarda Symptoms After Initiation of Antiviral Therapy

Infection with hepatitis C (HCV) predisposes to both development and exacerbation of porphyria cutanea tarda (PCT). However, antiviral therapy for HCV has classically been deferred in patients with PCT until after PCT control has been achieved with phlebotomy or low-dose hydroxychloroquine.¹

We present a patient with chronic HCV and active PCT who experienced rapid clinical resolution of PCT symptoms, without relapse at 12-month follow-up, after initiating treatment with a direct-acting antiviral agent (DAA) leading to sustained viral response (SVR) with undetectable HCV viral load. This case provides further support for the use of DAAs in the initial management of PCT in patients with chronic HCV. 

Case Report
A sexagenarian man with a history of polysubstance abuse and chronic, active HCV without cirrhosis was referred to our dermatology clinic for recurrent acral blisters exacerbated with sun exposure and alcohol intake. Punch biopsy of a bulla on the right fifth finger showed a noninflammatory, subepidermal blister. Direct immunofluorescence showed IgG/IgM deposition along the dermoepidermal junction and papillary vessels. Initial treatment with phlebotomy led to incomplete improvement with decreased frequency and intensity of flares.

After being lost to follow up for multiple years, the patient returned to the clinic due to development of a dental sinus. At that time, physical exam was significant for tense digital bullae; zygomatic hypertrichosis; sclerodermoid changes of the chin, neck, and upper chest; and evidence of prior insults on his dorsal hands and fingers in the form of atrophic changes, healing erosions, milia, and scarring (Figure). Testing showed hemoglobin of 17.0 g/dL, platelet count of 233 K/cm³, HCV viral load of 49,700 IU/mL, elevated ferritin of 362.7 ng/mL, and elevated total serum porphyrins at 11.3 ug/dL.

The patient was referred to the hepatology clinic where
antiviral therapy was initiated for HCV. After 1 month of therapy with ledipasvir/sofosbuvir (90 mg/400 mg), his viral load was undetectable and his blisters resolved. At 12-month follow-up, the patient had SVR with undetectable HCV viral load, was free of bullae, and denied experiencing any flares since starting antiviral therapy. 

Discussion
PCT is the most common type of porphyria, characterized by skin fragility and photodistributed blister formation, often with postinflammatory hyperpigmentation and scarring. PCT is caused by deficient activity of the enzyme uroporphyrinogen decarboxylase in the heme synthesis pathway, leading to porphyrin accumulation.² HCV is a risk factor for both PCT development and exacerbation, which is present in approximately 50% to 70% of PCT cases in North America.1 Classically, HCV treatment has been deferred in patients with PCT until after initial management of PCT with phlebotomy or hydroxychloroquine due to associations between older HCV therapies and worsening, relapse, or first appearance of PCT symptoms, as well as decreased efficacy of interferon-based HCV regimens in patients with active PCT.¹ However, compared with prior treatment options, DAAs are associated with fewer adverse effects and significantly higher rates of achievement of SVR with undetectable HCV viral load.¹ Recent case reports and small case series have suggested that DAAs may be a viable alternative to phlebotomy or hydroxychloroquine in the initial management of PCT in patients with chronic HCV.^1,3-5

The patient presented in this report experienced rapid clinical resolution of his PCT symptoms without relapse at 12-month follow-up after initiation of treatment with a DAA, leading to SVR with undetectable HCV viral load. This represents further support for the use of DAAs in the initial management of PCT in this patient population. Of note, the first clinical trial evaluating the use of DAAs for this purpose is currently being conducted at Wake Forest University with an estimated study completion date of August 2024.⁶ 

Dr Morris is a resident physician at the department of dermatology at University of Oklahoma Health Sciences Center in Oklahoma City. Ms Levin is a fourth-year medical student at Paul L. Foster School of Medicine at Texas Tech University Health Sciences Center El Paso in Texas. Dr Levin is an assistant professor of dermatology at the department of dermatology at University of Oklahoma Health Sciences Center.

Disclosure: The authors report no relevant financial relationships.

References
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2. Frank J, Poblete-Gutiérrez PA, Lang E. Porphyria. In: Bolognia JL, Schaffer JV, Cerroni L. Dermatology. 4th ed. Elsevier; 2018.

3. Combalia A, To-Figueras J, Laguno M, Martínez-Rebollar M, Aguilera P. Direct-acting antivirals for hepatitis C virus induce a rapid clinical and biochemical remission of porphyria cutanea tarda. Br J Dermatol. 2017;177(5):e183-e184. doi:10.1111/bjd.15502

4. Bruzzone B, Magnani O, Sticchi L, et al. Resolution of porphyria cutanea tarda in HIV and mixed HCV coinfection after direct-acting antiviral (DAA) therapy.

J Antimicrob Chemother. 2017;72(10):2955-2958. doi:10.1093/jac/dkx222

5. Takata K, Shakado S, Sakamoto K, et al. Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C. Clin J Gastroenterol. 2017;10(5):459-463. doi:10.1007/s12328-017-0772-x

6. Harvoni Treatment Porphyria Cutanea Tarda. ClinicalTrials.gov identifier: NCT03118674. July 24, 2020. Accessed August 27, 2020. https://clinicaltrials.gov/ct2/show/NCT03118674