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| LETTER TO THE EDITOR |
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| Year : 2020 | Volume
: 7
| Issue : 2 | Page : 106-107 |
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Bleomycin-induced flagellate dermatitis
Abheek Sil, Dibyendu B Bhanja, Sayantani Chakraborty
Department of Dermatology, Venereology, and Leprosy, R.G. Kar Medical College, Kolkata, West Bengal, India
| Date of Submission | 02-Mar-2020 |
| Date of Decision | 22-Mar-2020 |
| Date of Acceptance | 21-Jul-2020 |
| Date of Web Publication | 03-Dec-2020 |
Correspondence Address:
Dr. Abheek Sil
Department of Dermatology, Venereology, and Leprosy, R.G. Kar Medical College, 1, Khudiram Bose Sarani, Kolkata 700004
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/Pigmentinternational.Pigmentinternational_
Flagellate pigmentation represents a unique adverse effect of bleomycin therapy that is encountered in 8–22% of patients. But this occurrence is independent of dose, route of administration, and underlying disorder (including type of malignancy). We highlight a case of a middle-aged man who developed flagellate hyperpigmentation following bleomycin-containing combined chemotherapy for Hodgkin’s lymphoma. Early recognition of bleomycin as the culprit drug is of paramount importance as these patients are usually on multiple medications.
Keywords: Adverse drug reaction, bleomycin, flagellate pigmentation
How to cite this article:
Sil A, Bhanja DB, Chakraborty S. Bleomycin-induced flagellate dermatitis. Pigment Int 2020;7:106-7 |
Dear Editor,
Bleomycin is a commonly used cytotoxic antibiotic for lymphoma, germ cell tumours and malignant pleural effusion. Additionally, it has been utilized intralesionally for treatment of warts or sclerotherapy for vascular malformations. Flagellate or streaked hyperpigmentation, first recognized in 1970,[1] is a characteristic but relatively uncommon cutaneous adverse effect of systemic or intralesional bleomycin.
A 33-year-old gentleman suffering from Hodgkin’s lymphoma (Stage III1B) on a chemotherapeutic regimen comprising doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) presented with itchy, whiplash-like rash over his arms and back, 10 days after receiving the fourth chemotherapy session. Within 12 hours of onset of initial pruritus and linear wheals, reddish-brown rash was seen over his left upper arm. In a span of a few days, the lesions became darker and progressed to involve the upper limbs and back. He denied ingestion of shitake mushrooms or history suggestive of any systemic involvement. Cutaneous examination revealed multiple, well-delineated linear hyperpigmented streaks (ranging from 4 to 12 cm in length; 3 to 8 cm in width) without associated scales distributed haphazardly over bilateral arms, forearms, nape of neck and entire back [Figure 1]. Histopathological analysis from lesion over upper back showed basal layer hyperpigmentation with mild superficial perivascular mononuclear cell infiltration [Figure 2]. The unique clinical presentation, temporal association with bleomycin, and corroborative histopathogical finding confirmed the diagnosis of bleomycin-induced flagellate pigmentation. Topical clobetasol propionate (0.05%) ointment twice daily and daily oral levocetirizine (5 mg) for 3 weeks led to symptomatic relief but the pigmentation persisted. His treating oncologist was recommended to consider a bleomycin sparing regimen. However, considering the importance of bleomycin as a part of the ongoing chemotherapeutic regimen, the cutaneous adverse reaction was not considered severe enough to warrant discontinuation of the treatment protocol. | Figure 2 Histopathology showing hyperpigmentation of basal layer with superficial perivascular mononuclear cell infiltration (H&E, x100).
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Cutaneous reactions secondary to bleomycin form an uncommon group of side-effects compared to the drug’s pulmonary toxicity. Skin demonstrates decreased activity of hydrolases required for inactivation of bleomycin, which explains the corresponding dermatological complications. Bleomycin has been reported to cause alopecia, stomatitis, hyperpigmentation, oedema, nail changes, Raynaud’s phenomenon leading to digital gangrene, verrucous plaques over knees and elbows, painful nodules on fingers and sclerodermoid changes.[1] The streaked or flagellate pigmentation represents a unique adverse effect of bleomycin therapy, encountered in 8–22 % of patients, independent of dose, route of administration, and type of underlying malignancy. However, flagellate hyperpigmentation has also been documented secondary to docetaxel, bendamustine, peplomycin (bleomycin derivative), shitake mushrooms, jellyfish stings, poison ivy, dermatographism, chikungunya fever, adult-onset Still’s disease, and dermatomyositis.[2],[3] Although the exact pathogenesis of bleomycin-induced pigmentation remains obscure, proposed hypotheses include increased localized melanogenesis, leakage of the drug due to scratching and alterations to normal pigmentary patterns secondary to inflammation.[4]
Flagellate pigmentation normally appears from day 1 to 9 weeks after drug administration; cumulative doses of 100-300 mg is warranted although doses as low as 15 to 30 mg have been reported to cause pigmented streaks following intralesional bleomycin therapy.[5]
Treatment does not dictate discontinuation of bleomycin (after risk-benefit analysis) but rather warrants providing symptomatic relief with topical corticosteroids and antihistaminics. The condition is self-resolving, albeit unavoidable residual hyperpigmentation, but can recur with drug rechallenge. In our patient, patch-test or rechallenge with bleomycin could not be performed as the patient did not consent to the procedure.
We emphasize the early recognition of bleomycin as the culprit drug causing flagellate dermatitis, as these patients are usually on multiple medications. Considering the not-so-severe nature of this adverse cutaneous reaction, adoption of a bleomycin-sparing regimen seems unwarranted. However, the analysis of its significance in the context of the patient’s underlying medical ailment should be undertaken only in consultation with treating oncologist.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Yamamoto T, Nishioka K. Flagellate erythema. Int J Dermatol 2006;45:627-31.  |
| 2. | Bhushan P, Manjul P, Baliyan V. Flagellate dermatoses. Indian J Dermatol Venereol Leprol 2014;80:149-52. [ PUBMED] [Full text] |
| 3. | Basu D, Podder I, Das A. Bleomycin-induced flagellate hyperpigmentation: A case report with review of literature. Pigment Int 2016;3:40-2. [Full text] |
| 4. | Khmamouche MR, Debbagh A, Mahfoud T, Aassab R, Lkhoyaali S, Ichou M et al. Flagellate erythema secondary to bleomycin: a new case report and review of the literature. J Drugs Dermatol 2014;13:983-4. |
| 5. | Yamamoto T. Bleomycin and the skin. Br J Dermatol 2006;155:869-75. |
[Figure 1], [Figure 2]
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