A rare manifestation – Bleomycin-induced skin toxicity

INTRODUCTION

Bleomycin, an anticancer glycopeptide antibiotic, was discovered in 1962 by Umezawa from Streptomyces verticillus.^[1] It is commonly used in treating Hodgkin’s lymphoma, germ cell tumours and malignant pleural effusion. Bleomycin induces DNA strand breaks, leading to apoptosis in rapidly dividing cancer cells.^[2]

Although pulmonary toxicity is the most recognised adverse effect, cutaneous manifestations are significant yet underreported. Bleomycin-induced dermatologic toxicities include hyperkeratosis, Raynaud’s phenomenon, nail bed changes and palmoplantar desquamation. The most distinctive presentation is flagellate hyperpigmentation, characterised by linear or streaked hyperpigmented lesions, primarily on the trunk and extremities.

The pathogenesis of bleomycin-induced skin toxicity is attributed to its poor detoxification in the skin due to a lack of bleomycin hydrolase, leading to oxidative stress and DNA damage.^[3,4] This report presents a case of flagellate pigmentation secondary to bleomycin therapy and discusses its clinical implications.

CASE REPORT

A 25-year-old male diagnosed with classical Hodgkin’s lymphoma (nodular sclerosis) was undergoing adriamycin, bleomycin, vincristine and dacarbazine chemotherapy, which included doxorubicin 47 mg, bleomycin 19 U, vinblastine 10 mg/m² and dacarbazine 700 mg, administered intravenously on days 1 and 15.

On the 3^rd day of his fifth chemotherapy cycle, he developed multiple pruritic, erythematous plaques on his neck, chest and trunk [Figure 1]. Some lesions exhibited a linear, streaked appearance characteristic of flagellate [Figure 2] hyperpigmentation.^[5] There was no associated fever, mucosal involvement or systemic symptoms.

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Figure 1:

Erythematous lesions with bleomycin.

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Figure 2:

Flagellate rash with bleomycin.

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Given the absence of alternative aetiologies, drug-induced skin toxicity was suspected. Bleomycin was discontinued, and systemic corticosteroids and antihistamines were initiated, gradually resolving the lesions. The causality assessment confirmed the reaction as probable/likely, reinforcing the need for permanent discontinuation of bleomycin. The patient continued with adriamycin, vinblastine, and dacarbazine (AVD) chemotherapy until cycle 8.

DISCUSSION

While pulmonary toxicity remains the most feared complication of bleomycin, skin manifestations should not be overlooked. Flagellate hyperpigmentation, a hallmark of bleomycin-induced skin toxicity, is thought to be caused by localised oxidative stress and inflammatory responses due to drug accumulation.^[7]

This reaction typically develops within days to weeks after administration and may persist for months or indefinitely. The severity is dose-dependent, with cumulative doses exceeding 200 units more likely to cause significant toxicity.^[8]

Additional cutaneous reactions include:

• Diffuse hyperpigmented macules and patches^[9]

• Sclerodermoid changes resembling graft-versus-host disease

• Infiltrated violaceous plaques and erythema multiforme-like eruptions^[9,10]

• Raynaud’s phenomenon in patients with concurrent vascular risk factors^[11]

• Palmoplantar desquamation, mimicking toxic epidermal necrolysis.^[12]

Early recognition of bleomycin-induced skin toxicity is crucial, as continued exposure can exacerbate symptoms and lead to permanent hyperpigmentation or fibrosis.^[13] Clinicians should maintain a high index of suspicion for this reaction and consider dose modification or discontinuation when necessary.

CONCLUSION

Bleomycin-induced skin toxicity is a rare but significant adverse effect requiring prompt recognition and management. While hyperpigmentation is often self-limited, permanent skin changes can occur. Early withdrawal of bleomycin in affected patients can prevent progression to severe dermatologic complications. Clinicians must educate patients about potential cutaneous side effects and closely monitor skin changes throughout therapy.