Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT.

What was known?

Human immunodeficiency virus infected patients of porphyria cutanea tarda are often co-infected with hepatitis C virus.

Introduction

Porphyrias, a group of rare acquired or hereditary diseases, occur due to deficiency or decreased activity of one of the eight enzymes in the heme biosynthesis pathway. Porphyria cutanea tarda (PCT), first described in 1911, is the most common of all porphyrias and occurs due to the deficiency of uroporphyrinogen decarboxylase (UROD).[1]

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are probable etiologic factors for the development of a sporadic form of PCT. Literature reviews show that almost all HIV-infected patients with PCT previously described had additional risk factors for PCT like coinfection with HCV.[2] Here, we report a case of PCT in an HIV-infected patient who tested negative for HCV indicating that HIV could be an independent risk factor for PCT.

Case Report

A 36-year-old married male presented to us with blistering over sunexposed parts of his body for 1 year and expectoration of blood-tinged sputum for 2 months. History of photosensitivity was present. The patient gave a history of intravenous drug abuse and chronic alcoholism. The patient had tested HIV positive 3 years ago and was on anti-retroviral therapy (ART) with tenofovir, lamivudine and lopinavir/ritonavir and his CD4 count at the time of presentation was 43 cells/mm3. His medical history was not suggestive of any preexisting liver disease. There was no history of similar blistering and liver disease in his family.

General examination of the patient revealed pallor and icterus. On abdominal palpation, hepatosplenomegaly was found. Cutaneous examination revealed blisters and erosions on face and dorsum of both hands. Few areas showed erosions, crusts, and healing with dyspigmentation and scar formation [Figures 1 and 2]. Hyperpigmentation of sun exposed parts and hypertrichosis of face was seen. Mucosa and hair were normal. Onychodystrophy was seen.

Figure 1

Crusts and scars over dorsa of hands and face

Figure 2

Crusts, scars, and bulla over dorsa of hands

Routine hemogram and serum biochemistry revealed: Hemoglobin 7.8 g/dl, total bilirubin 3.4 mg/dl, serum glutamic oxalacetic transaminase 185 U/L, serum glutamic pyruvic transaminase 37 U/L, alkaline phosphatase 871 U/L, gamma glutamyl transferase 760 U/L, serum iron 55 mcg/dl, total iron binding capacity 136 mcg/dl, and transferrin saturation 40.4%. Serological screening for hepatitis B and C was negative. Gram-staining and culture and sensitivity of sputum showed the presence of Pseudomonas aeruginosa. Ultrasound of abdomen revealed hepatosplenomegaly.

Examination of urine under Wood's light showed pink fluorescence consistent with the presence of porphyrins [Figure 3]. Urinary porphyrin level was elevated. Histopathological examination from a blister revealed normal epidermis, cell-poor sub-epidermal bulla, and festooning of dermal papillae inside the bulla [Figure 4]. Based on clinical and histopathological findings a diagnosis of PCT was made.

Figure 3

Pink fluorescence seen on wood's lamp examination of urine

Figure 4

Histopathology showing sub-epidermal, cell-poor bulla with festooning of papilla (H and E, ×100)

Discussion

PCT is a disorder of heme synthesis and occurs due to a deficiency of enzyme UROD. It usually becomes apparent during the fourth or fifth decade of life but can also present earlier. The two main sites of heme synthesis are erythrocytes and the liver. A decrease in the activity of UROD, therefore, leads to accumulation of uroporphyrin and other highly carboxylated porphyrins in various organs, most commonly the liver and skin characterized by reduced activity of the enzyme in the hepatocytes (type I/sporadic/acquired form) or in both erythrocytes and hepatocytes (type II/familial form).[3] Currently, the ratio of type I to type II PCT is estimated to be approximately 3:1–4:1.[4]

PCT is characterized by photosensitivity, vesicles and bullae, followed by erosions and crusting produced in areas subjected to repeated trauma. As the lesions resolve, areas of scarring may ensue. Other skin changes include hypertrichosis, hyperpigmentation, and sclerodermoid plaques.[5]

Dermatoses that can be confused with PCT include other porphyrias (variegate porphyria, hereditary coproporphyria, congenital erythropoietic porphyria), pseudoporphyria and epidermolysis bullosa acquisita.[5]

Histopathological findings in PCT are a subepidermal bulla showing festooning of the base with little/no inflammatory infiltrate. These findings are characteristic but not exclusive for PCT as they can be found in pseudoporphyria as well.[5] The diagnosis of PCT can be confirmed by high serum porphyrins, increased excretion of urinary uroporphyrin and fecal copro and isocoproporphyrin.[6]

The most recognized factors that precipitate acquired PCT are ethanol abuse, hepatic siderosis, exposure to toxins (e.g., polychlorinated biphenyls, hexachlorobenzene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin), several medications (anticonvulsants, iron supplements, sulfonamides, estrogens, zidovudine, or indinavir) and viral infections (HCV and HIV).[1]

HIV infection can precipitate PCT by several mechanisms. It affects porphyrin metabolism by reducing the ability of the cytochrome P450–dependent mixed-function oxidase system, which is needed to detoxify chemicals and causes ineffective erythropoiesis, resulting in hepatic iron overload. Moreover, HIV-infected individuals may have increased estrogen production due to altered steroid metabolism, thereby disrupting heme synthesis and eventually leading to PCT.[7]

In 1987, Wissel et al. were the first to report three cases of PCT associated with HIV infection.[8] Mansourati et al. later in the same year reviewed 75 reported cases of HIV infection with PCT. Almost all (96%) of them were male. At the time of diagnosis, mean age was 36.5 years and the mean CD4 count was 166 cells/mm3. Forty-five percent of patients had coinfection with HCV, 55% consumed alcohol heavily, and 89% had abnormal liver function tests. The diagnosis of PCT preceded the detection of HIV infection in 40% cases.[9] Another report states that although PCT in HIV-infected persons develops and may be diagnosed a decade earlier as compared to non-HIV-infected persons, it may also be diagnosed concurrently or later, suggesting that HIV per se and not reduced immune status precipitates porphyria.[1]

The literature review showed six cases of PCT associated with highly active ART (HAART).[10] However, the interval from the first administration of HAART treatment to the onset of PCT ranged from 3 days to 4 months. Since our patient developed features of PCT after almost 3 years of HAART, it is unlikely that PCT in him was precipitated by HAART.

Our patient was put on low dose hydroxychloroquine (200 mg twice weekly) and counseled for strict photoprotection and alcohol abstinence. ART was asked to be continued as before.

Conclusion

Not many cases of coexistence of PCT and HIV infection have been reported from India.[13] A diagnosis of PCT should prompt a comprehensive workup for HIV infection, and similarly porphyrin studies must be performed in patients diagnosed with HIV and photosensitivity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Human immunodeficiency virus (HIV) is an independent risk factor for porphyria cutanea tarda; hence all patients of porphyria must be worked up for HIV and vice versa.