Porphyria cutanea tarda in a middle-aged man with alcohol consumption

INTRODUCTION

Porphyrias are a group of metabolic disorders that arise from abnormal heme biosynthesis, leading to the accumulation of porphyrins and their precursors. Porphyria cutanea tarda (PCT) is the most prevalent subtype, accounting for up to 80% of all cases. PCT is characterized by the accumulation of uroporphyrinogen in the liver, resulting in impaired heme synthesis and the consequent accumulation of porphyrins in the skin. Triggers for PCT can include alcohol consumption, hepatitis C infection, and exposure to certain drugs or chemicals. Herein, we present a case of PCT in a middle-aged man with a history of alcohol use.^[1]

CASE REPORT

A 42-year-old man with a history of regular alcohol intake reported tense blisters, scarring, and milia on both hands and forearms following a family vacation at a tropical beach resort where he was exposed to prolonged sun exposure. The patient denied any recent exposure to drugs or chemicals and had no prior history of skin conditions or blistering disorders. However, on detailed questioning, the patient revealed that he habitually consumed 240–300 mL of alcohol daily or nearly daily [Figure 1].

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Figure 1:

Tense blisters with scarring and milia on the dorsal aspects of both hands.

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On examination, the patient had multiple blisters of various sizes in the sun-exposed acral areas, including both hands and forearms. Blisters were tense and tender on touch. Careful examination showed a few erosions from ruptured blisters and also the presence of scarring and milia in the previous blister areas.

A biopsy was performed from an intact blister and perilesional skin on the patient’s left forearm. Histopathological analysis showed a pauci-cellular subepidermal bulla. The dermal papilla showed few slender protrusions into the bullous space. The dermal blood vessel showed moderate mononuclear cell infiltration around blood vessels. The basement membrane zone (BMZ) appeared thickened. The dermis showed mild inflammation [Figure 2a-c]. Periodic acid–Schiff stain showed thickening of the BMZ [Figure 2d].

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Figure 2:

(a) Hematoxylin and eosin (H&E) stain ×40 magnification photomicrograph showing a pauci-cellular subepidermal bulla. (b) H&E stain ×100 magnification photomicrograph showing slender protrusions of dermal papilla into the bullous space. (c) H&E stain ×400 magnification photomicrograph showing moderate mononuclear cell infiltration around blood vessels. (d) Periodic acid–Schiff stain ×100 magnification photomicrograph showing thickening of the basement membrane zone.

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Direct immunofluorescence (DIF) revealed intense homogeneous deposits in the blood vessels of the papillary dermis and granular deposits at the BMZ of immunoglobulin G (IgG), immunoglobulin A, and C3 [Figure 3a and b]. Further investigations revealed moderately elevated liver enzymes, including aspartate aminotransferase 68 U/L (normal 0–50), alanine aminotransferase 54 U/L (normal 0–50), gamma-glutamyltransferase 230 U/L (normal 0–55), and alkaline phosphatase 92 U/L (normal 30–120). Tests for hepatitis C, hepatitis B, and human immunodeficiency virus were negative, and autoimmune screening revealed normal levels of anti-thyroid, anti-nuclear, and rheumatoid antibodies. His porphyrin (24-hour urine) concentration was 340 μg/24 hours (normal ≤100), and porphobilinogen (24-hour urine) was 2.09 mg/24 h (normal ≤1.50).

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Figure 3:

(a) Direct immunofluorescence (DIF) photomicrograph showing intense granular deposits of immunoglobulin G (IgG) at the basement membrane zone. (b) DIF photomicrograph showing intense homogeneous deposits of IgG in the blood vessels of the papillary dermis.

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Based on these findings, a diagnosis of PCT was established, and the patient was advised to discontinue alcohol consumption.

We initiated photoprotection with regular sunscreen use and started the patient on hydroxychloroquine (HCQ) 300 mg daily. The patient was referred to the hematology department for further evaluation and potential phlebotomy. After assessing hepatic and iron profiles, the hematologist commenced weekly phlebotomy to reduce iron stores. Following its initiation, the HCQ dose was tapered to 200 mg on alternate days and discontinued after a month. Upon reassessment after three phlebotomy sessions, the patient’s skin condition improved, with no new blister formation and healing of old blisters with mild scarring [Figure 4]. The patient remained under hepatology care, with improving liver function parameters.

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Figure 4:

Marked improvement after three phlebotomy sessions.

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DISCUSSION

PCT is a complex and rare condition that can be triggered by a variety of factors such as hepatitis C infection, exposure to certain drugs and chemicals, and alcohol consumption, a well-known risk factor. The pathology of PCT is associated with significantly reduced hepatic uroporphyrinogen decarboxylase (UROD) activity and decreased erythrocyte UROD activity, leading to iron overload in the liver and liver damage. In addition, an oxidized form of uroporphyrinogen, uroporphomethene, contributes to decreased UROD enzyme activity, which is vital to metabolizing porphyrins. Low functional UROD levels cause the abnormal accumulation of porphyrins in the blood, liver, and skin, leading to PCT symptoms. The abnormal accumulation of porphyrin and related chemicals might cause toxic damage when they accumulate in the liver, further worsening the condition.^[2] Several medications have also been reported to be associated with PCT [Table 1].

In our case, the patient’s history of habitual alcohol consumption, a well-known trigger for PCT, further complicates the condition. The patient’s liver is likely under significant stress due to the accumulation of porphyrins, iron overload, and the hepatotoxic effects of alcohol. These factors can cause a wide range of symptoms, including cutaneous manifestations such as blistering and hyperpigmentation, as well as hepatic dysfunction. Therefore, it is crucial to diagnose PCT early and manage it effectively to prevent the progression of the disease and the development of hepatic complications.

The diagnosis of PCT is based on clinical presentation, histopathology, and laboratory investigations. PCT usually presents with recurrent skin blisters in photo-exposed parts such as the hands and face, and patients may have extreme photosensitivity. Scars might develop, or the skin can get thicker and harder, commonly referred to as pseudosclerosis.^[3] We considered various differential diagnoses, including epidermolysis bullosa acquisita (EBA), bullous pemphigoid (BP), bullous lupus erythematosus, hydroa vacciniforme, and erythropoietic protoporphyria. A skin biopsy is a commonly used diagnostic tool for PCT. It can reveal subepidermal bullae with perivascular and peri-adnexal lymphocytic infiltrates. Furthermore, immunofluorescence can aid in confirming the diagnosis by demonstrating the deposition of IgG and C3 along the BMZ.^[4] PCT is a complex condition that can affect the liver and cause a variety of liver-related symptoms such as hepatic siderosis, steatosis, portal triaditis, and periportal fibrosis. The liver damage associated with PCT may present as elevated liver enzymes or even liver cancer. Alcohol consumption can further complicate PCT symptoms, as it increases iron absorption and stimulates hepatic q-aminolevulinate synthase (ALA), leading to free radical production and independent hepatotoxicity.^[5]

It is crucial to diagnose and manage PCT early, as the condition can progress and lead to severe hepatic complications. The complexity of PCT highlights the importance of identifying and addressing the underlying triggers that contribute to the condition, such as hepatitis C infection and exposure to certain drugs and chemicals. DIF is crucial in differentiating PCT from BP and EBA by revealing distinct immunoreactant deposition patterns, with BP showing linear n-serrated IgG/C3 at the BMZ, EBA displaying u-serrated IgG deposition, and PCT demonstrating variable granular or mixed immunoreactant patterns along the BMZ and perivascular regions.^[6] Effective management of PCT requires a multidisciplinary approach involving the expertise of healthcare professionals from various disciplines, including hepatology, dermatology, and hematology.^[7]

PCT management aims to decrease the accumulation of porphyrins in the liver and other organs to alleviate cutaneous symptoms and prevent hepatic complications. Phlebotomy, which involves the removal of a unit of blood every 1–2 weeks until the serum ferritin level reaches a target of 20–50 ng/mL, is the most effective and widely used treatment. This reduces iron stores in the liver, which can decrease the synthesis of porphyrins. The frequency of phlebotomy can be reduced once the serum ferritin level has been stabilized. Phlebotomy can also improve hepatic function and reduce the risk of hepatocellular carcinoma.^[7]

Low-dose HCQ can be used to enhance the effectiveness of treatment by increasing the excretion of porphyrins in the urine. Chloroquine, however, is not recommended in patients with severe hepatic disease due to its potential hepatotoxicity. Liver transplantation is an option for patients with advanced liver disease or hepatocellular carcinoma, but it is reserved for those who have failed or are not suitable for other treatments.^[8] Lifestyle modifications can also be beneficial for managing PCT. Patients should avoid alcohol, which can exacerbate the symptoms of PCT by increasing hepatic q-ALA and iron absorption, leading to porphyrin accumulation in the liver. Using sunscreen and avoiding excessive exposure to sunlight can help prevent cutaneous manifestations.

In summary, the management of PCT involves a combination of phlebotomy, HCQ, liver transplantation, and lifestyle modifications. The use of these management options can help alleviate cutaneous symptoms and prevent hepatic complications associated with PCT.^[7,9-12]

CONCLUSION

PCT is a rare cutaneous porphyria associated with impaired heme synthesis. It is often associated with triggers such as alcohol consumption, hepatitis C infection, and exposure to certain drugs and chemicals. Early diagnosis and prompt treatment are essential in the management of PCT. Phlebotomy is an effective treatment option that can reduce iron stores and prevent the accumulation of porphyrins in the skin. PCT is an uncommonly reported and poorly recognized entity in India. Our case emphasizes that early diagnosis and treatment can prevent the progression of the disease and reduce the risk of hepatic complications.