Challenges in Porphyria diagnosis and management: When variegate Porphyria meets HIV

Variegate Porphyria (VP) is a rare autosomal dominant disorder characterized by deficient activity of protoporphyrinogen oxidase, resulting in the accumulation of potentially neurotoxic heme precursors. We present the case of a 32-year-old woman with HIV receiving antiretroviral therapy (dolutegravir, lamivudine, and ritonavir) who had generalized seizures, psychosis, and polyneuropathy, initially interpreted as secondary to infection. Brain magnetic resonance imaging suggested vasogenic edema, raising suspicion of autoimmune encephalitis. Despite treatment with methylprednisolone and intravenous immunoglobulins, her health worsened, requiring intensive care and extended mechanical ventilation. Markedly elevated urinary porphyrin precursors and porphyrins, a characteristic pattern of elevated fecal porphyrins, and a plasma fluorescence emission peak at 626 nm were diagnostic for VP. Genetic testing identified a pathogenic PPOX missense variant NM_001365398.1:c.428 A > T, p.(Asp143Val), consistent with VP. The patient required repeated courses of hemin and intravenous dextrose, which were followed by transient biochemical improvement. However, symptoms and biochemical markers recurred over time. Clinical stability was only achieved after the withdrawal of ritonavir from her antiretroviral regimen, emphasizing the need for careful medication review in patients with Acute Hepatic Porphyria. This case shows the complex interactions between genetic predisposition, environmental factors, and comorbidities in VP, emphasizing the importance of genetic and biochemical testing for accurate diagnosis, hemin administration during acute attacks, and careful medication review. Clinicians should remain vigilant about interactions between antiretroviral therapy and porphyria when treating HIV-positive patients with suspected or confirmed Acute Hepatic Porphyria.