Bleomycin-induced flagellate dermatitis in a South Indian patient with Hodgkin’s Lymphoma – A case report

INTRODUCTION

Flagellate dermatoses are rare skin conditions characterised by linear or curvilinear lesions resembling whip marks.^[1] Bleomycin is a cytotoxic glycopeptide antibiotic, originally isolated from Streptomyces verticillus by Umezawa in Japan in 1966, and is widely used in the treatment of various malignancies, including squamous cell carcinoma, lymphoma, testicular cancer, germ cell tumours, and malignant pleural effusions. In addition, dermatologists use it off-label to manage stubborn warts, hypertrophic scars, and keloids.^[2]

However, the drug’s use has declined due to notable adverse effects, such as pulmonary fibrosis, Raynaud’s phenomenon, alopecia, nail dystrophy, gangrene, oedema, and the distinctive cutaneous reaction known as flagellate dermatitis with a reported incidence between 8% and 66%.^[2] Bleomycin is frequently included in standard treatment protocols for Hodgkin lymphoma, such as the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) regimen.^[3]

The drug is metabolised by the bleomycin hydrolase, an enzyme notably deficient in the skin and lungs, which can lead to accumulation in these tissues and contribute to its toxic effects.^[3] Bleomycin’s cytotoxicity results from the formation of reactive oxygen species that cause deoxyribonucleic acid (DNA) strand breaks, ultimately disrupting replication and inducing cell death.^[4]

Clinically, bleomycin-induced flagellate dermatitis presents as widespread, itchy, red linear plaques most commonly over the trunk and limbs. These lesions can appear within hours to several months after administration and often resolve with residual hyperpigmentation, even in the absence of an active rash or itching. Although the exact pathogenesis remains uncertain, proposed mechanisms include minor skin trauma, inflammatory responses, increased melanin production, and decreased epidermal turnover, which extend interactions between melanocytes and keratinocytes.^[1,4] No specific treatment exists. However, discontinuing bleomycin usually leads to gradual improvement. Re-challenging the patient with bleomycin can provoke a more severe recurrence.^[5]

In this report, we present the case of a 35-year-old male with Hodgkin’s lymphoma who developed flagellate dermatitis following bleomycin-based chemotherapy.

CASE REPORT

A 35-year-old male patient diagnosed with Hodgkin’s lymphoma was scheduled to begin induction chemotherapy with the ABVD regimen, as per European Society for Medical Oncology guidelines^[6] outlined in Table 1. Accordingly, he received injection adriamycin 25 mg, injection bleomycin 10 mg, injection vinblastine 6 mg, and injection dacarbazine 520 mg once every 2 weeks.

Six days after receiving the first chemotherapy cycle, the patient developed intense pruritus and multiple excoriated, linear, hyperpigmented plaques over the arms, chest [Figure 1], and trunk [Figure 2].

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Figure 1:

Multiple, well-demarcated, hyperpigmented linear bleomycin-induced flagellate dermatitis on the arm and chest.

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Figure 2:

Hyperpigmented whip-like pattern seen on trunk.

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Based on clinical symptoms and complete examination, a dermatologist diagnosed bleomycin-induced flagellate dermatitis. The patient was started on clindamycin gel, adapalene plus clindamycin topical combination, an emollient lotion, an anti-acne cleansing bar, and oral levocetirizine 5 mg daily for 20 days. His symptoms improved progressively with treatment. Bleomycin therapy was continued.

DISCUSSION

We report a case of bleomycin-induced flagellate dermatitis in a 35-year-old male undergoing ABVD chemotherapy for Hodgkin’s lymphoma. Bleomycin, an antitumor antibiotic, exerts its primary effect by inducing single-stranded DNA breaks and disrupting DNA replication.^[7] After systemic administration, approximately half of the drug is excreted unchanged through the kidneys, while the rest is metabolised by bleomycin hydrolase – an enzyme notably deficient in the lungs and skin. This deficiency contributes to its pulmonary and cutaneous toxicities.^[8]

Flagellate dermatitis is a rare but recognised adverse effect of bleomycin, with reported incidence rates ranging from 8% to 22%.^[9] The reaction is considered dose-dependent and can occur regardless of the route of administration or the type of malignancy being treated. While it usually appears after a cumulative dose between 90 mg and 285 mg, cases have been observed with doses as low as 15 mg.^[10]

Skin lesions may develop from as early as the 1^st day of treatment to as late as 9 weeks post-administration, and symptoms can persist for several months.^[10] Even after resolution of the acute rash, flagellate-patterned hyperpigmentation may last for months to a year.^[11] Re-exposure to bleomycin can result in recurrence or worsening of the reaction. Furthermore, heat exposure has been reported to reactivate previously affected skin areas, emphasising the importance of preventive strategies such as cooling the skin before chemotherapy sessions.^[12,13]

There is no definitive treatment for bleomycin-induced flagellate dermatitis.^[14] Management is primarily supportive and symptom-based. Topical corticosteroids, oral antihistamines, and emollients are commonly used to relieve symptoms.^[14] In severe cases, discontinuation of bleomycin often leads to gradual resolution. Patients should be reassured about the self-limiting nature of the condition to reduce anxiety and improve adherence to chemotherapy.^[15]

Similar cases have been reported in North India. One such report described a 35-year-old female with an ovarian immature teratoma who developed hyperpigmented, whip-like lesions after a single 30 mg bleomycin dose. She was managed conservatively with topical corticosteroids and antihistamines, without discontinuing chemotherapy.^[16] Another case involved a 28-year-old male with Hodgkin’s lymphoma who developed typical flagellate hyperpigmentation following his first ABVD cycle. He also responded to topical treatment, and bleomycin was continued.^[17]

In light of these cases and our current report, it is crucial for clinicians to recognise this distinctive cutaneous reaction early. Timely identification and appropriate management can help avoid unnecessary discontinuation of an otherwise effective anticancer agent.

CONCLUSION

Bleomycin-induced flagellate dermatitis is an uncommon yet clinically recognisable dermatological adverse effect. This case emphasises the importance of clinical awareness, early diagnosis, and timely intervention. Treatment strategies may include topical emollients, corticosteroids, and systemic antihistamines, selected based on the severity of symptoms. Physicians should be mindful of this condition when prescribing bleomycin and counsel patients about its typically benign and self-limiting course. Raising awareness of this rare side effect is essential to ensure timely care and to avoid unnecessary discontinuation or overtreatment during chemotherapy. In patients receiving bleomycin for the 1^st time, regular skin monitoring during and after chemotherapy is recommended to facilitate early recognition and appropriate management of dermatologic complications.