Flagellate dermatitis is a rare cutaneous manifestation in which
long, striated erythematous lesion appear on the patient’s skin. It is most frequently
associated with bleomycin treatment or Shiitake mushroom intake,
but it may also be attributed to many other possible causes. Herein we present
a case of striated, hyperpigmented lesions which occurred after bleomycin
intake. The typical flagellate lesions appeared for the first time on the patient’s
back and shoulders after the first course of chemotherapy for seminoma
(bleomycin, etoposide, and cisplatin). The active lesions disappeared with
the discontinuation of chemotherapy. Clinicians should be aware of flagellate
pattern of dermatitis which may accompany different clinical situation

Krajewski, Piotr K.

Matusiak, Łukasz

Szepietowski, Jacek C.

English

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ACTA DERMATOVENEROLOGICA CROATICA102Flagellate Dermatitis due to Bleomycin IntakePiotr K. Krajewski, Łukasz Matusiak, Jacek C. SzepietowskiDepartment of Dermatology, Venereology and Allergology, Wroclaw Medical  University, Wroclaw, PolandCorresponding author:Prof. Jacek C Szepietowski, MD, PhDDepartment of Dermatology,  Venereology and AllergologyWroclaw Medical UniversityChalubinskiego 1 50-368 Wroclawjacek.szepietowski@umed.wroc.plReceived: February 17, 2021Accepted: June 15, 2021Acta Dermatovenerol Croat                              2021;29(2):102-104                                                 CASE REPORTABSTRACT Flagellate dermatitis is a rare cutaneous manifestation in which long, striated erythematous lesion appear on the patient’s skin. It is most fre-quently associated with bleomycin treatment or Shiitake mushroom intake, but it may also be attributed to many other possible causes. Herein we pres-ent a case of striated, hyperpigmented lesions which occurred after bleomycin intake. The typical flagellate lesions appeared for the first time on the patient’s back and shoulders after the first course of chemotherapy for seminoma (bleomycin, etoposide, and cisplatin). The active lesions disappeared with the discontinuation of chemotherapy. Clinicians should be aware of flagel-late pattern of dermatitis which may accompany different clinical situations.  KEY WORDS: flagellate dermatitis, testicular cancer, bleomycin, chemothera-py, drug eruption, adverse drug reactionConflict of interest:INTRODUCTIONFlagellate dermatitis, also called flagellate erythe-ma, is a term specific for a drug eruption which was firstly described by Moulin et al. (1) in 1970 as bleo-mycin-induced linear hyperpigmentation. Though the disease was initially associated with the use of bleomycin, more possible causes have been found since then that include Shitake mushrooms intake, chemotherapeutics (peplomycin, docetaxel), hype-reosinophilic syndrome, mechanical causes (torture), and rheumatological disorders (2). Flagellate derma-titis is often described as a dose-dependent reaction, which usually occurs with total doses above 100 U of bleomycin, but the lesions may also appear with very low, scintigraphy doses of 15 U (3,4). CASE REPORTA 33-year-old Caucasian man was referred to our Department due to multiple skin lesion affecting his back and shoulders. The patient reported that he had been treated for to testicular cancer (seminoma). Other than a history of neoplasm, he did not have any comorbidities and appeared to be in good gen-eral health. The patient was diagnosed with testicular cancer in July 2019, underwent radical orchiectomy, and was treated with chemotherapy (bleomycin, cis-platin, and etoposide regimen) for lymph nodes and pulmonary metastases. Before the second course of chemotherapy (September 2019), red lesions ap-peared on the patient’s back and shoulders, with associated xerosis. Their number increased with the next courses of the therapy. The patient did not report any itch nor pain. After completion of chemotherapy (November 2019), the lesions stopped spreading, gradually changed their color to brown, and per-sisted unchanged to date. On admission, physical ex-amination revealed multiple, linear hyperpigmented 103ACTA DERMATOVENEROLOGICA CROATICAKrajewski  et al. Acta Dermatovenerol CroatFlagellate dermatitis due to bleomycin intake  2021;29(2):102-104lesions (Figure 1) located on the shoulders and on the back. There was no evidence of mucosal or sys-temic involvement. The patient did not report any pathological sensation in the affected area. Flagellate dermatitis was diagnosed on the basis of the clinical picture and medical history. Nevertheless, due to the lack of subjective symptoms and no ongoing treat-ment with bleomycin, no treatment was prescribed.DISCUSSIONBleomycin is an antineoplastic agent which be-longs to a subfamily of glycopeptide antibiotics. It is frequently used as a part of cytotoxic chemotherapy regimens. Since its approval it has been used for Hodgkin’s lymphoma, squamous cell carcinoma, and testicular cancer. The primary mechanism of action is its ability to damage DNA. This breakdown of DNA and subsequent production of thymine causes cells to stop the cycle at the G2 phase (5). The adverse ef-fects of the therapy are mostly visible in tissues with relatively low levels of bleomycin hydrolase enzyme (lungs or skin) and are believed to be effects of drug accumulation (5). Drug-related skin manifestations are observed in the majority of patients (50-88%) and are in most cases reversible (3). Among the possible symptoms, the literature mentions alopecia, stoma-titis, painful and inflamed nodules or fingers, affecta-tion of nails, and flagellated erythematous infiltrates frequently associated with intense itch (3).The pathophysiology is yet to be fully discovered; however, local accumulations of bleomycin may play an important role in its development. A study by Takeda et al. (6) showed that bleomycin hydrolase is localized only in the subcorneal layers of the epider-mis, and the drug thus cannot be fully degraded at the dermal levels. Moreover, bleomycin-induced skin changes often appear on the extremities and over bony prominences, and it is believed that trauma-related blood flow increases the accumulation of the drug (3). The lesions vary and may appear as striated ery-thematous, urticarial, but also papular and vesicular skin changes, which tend to heal with subsequent hyperpigmentation (3). Although the lesions are of-ten pruritic, our patient did not report any pathologi-cal sensation at any point of the therapy or after its completion. The time of development varies greatly, and in some cases it may start several hours after the drug introduction while in others it may take up to two months (3). The diagnosis is established mostly based on the clinical picture. The association of skin manifestations with drug administration and hyperpigmentation af-ter drug suspension is typical (7). Although it has been reported that histopathological findings in flagellate dermatitis are similar to fixed drug eruptions (8), re-cent studies have indicated that the histological pic-ture is neither specific nor uniform (3). The differential diagnosis mostly includes other causes of flagellate dermatitis, including Shitake mushroom intake (9).There is no specific treatment available. Normally, lesions clear in 6-8 months after the suspension of bleomycin. In some patients the chemotherapy may be continued without bleomycin, but this decision has to be made on the basis of risk-benefit analysis (10). The treatment of the associated pruritus may in-clude topical and systemic corticosteroids as well as oral antihistamine drugs. These have been reported to be beneficial to relieving pruritus and decreasing skin trauma (10).Figure 1. Lesions on the patient’s shoulder (A and B) and back (C).ACTA DERMATOVENEROLOGICA CROATICA104Flagellate dermatitis is an uncommon skin mani-festation of bleomycin therapy. We believe that all cli-nicians should be aware of this manifestation in order to act appropriately against this adverse reaction.References:1. Moulin G, Fière B, Beyvin A. Pigmentation cutanée par la bléomycine [Cutaneous pigmentation cau-sed by bleomycin]. Bull Soc Fr Dermatol Syphiligr. 1970;77:293-6.2. Bhushan P, Manjul P, Baliyan V. Flagellate der-matoses. Indian J Dermatol Venereol Leprol. 2014;80:149-52.3. Ziemer M, Goetze S, Juhasz K, Elsner P. Flagellate dermatitis as a bleomycin-specific adverse effect of cytostatic therapy: a clinical-histopathologic correlation. Am J Clin Dermatol. 2011;12:68-76.4. Perrot H, Ortonne JP. Hyperpigmentation after bleomycin therapy. Archives of Dermatological Research. 1978;261:245-52.5. Brandt JP, Gerriets V. Bleomycin. StatPearls [Inter-net]: Treasure Island (FL): StatPearls Publishing; 2020 Jan.6. Takeda A, Nonaka M, Ishikawa A, Higuchi D. Im-munohistochemical localization of the neutral cysteine protease bleomycin hydrolase in human skin. Arch Dermatol Res. 1999;291:238-40.7. Grynszpan R, Niemeyer-Corbellini JP, Lopes MS, Ra-mos-e-Silva M. Bleomycin-induced flagellate der-matitis. BMJ Case Rep. 2013;2013:bcr2013009764.8. Mowad CM, Nguyen TV, Elenitsas R, Leyden JJ. Bleomycin-induced flagellate dermatitis: a clini-cal and histopathological review. Br J Dermatol. 1994;131:700-2.9. Baran W, Batycka-Baran A, Maj J, Szepietowski JC. Shiitake dermatitis - now also in Poland. Acta Derm Venereol. 2015;95:102-3.10. Jones RH, Vasey PA. Part II: testicular cancer--ma-nagement of advanced disease. Lancet Oncol. 2003;4:738-47.Krajewski  et al. Acta Dermatovenerol CroatFlagellate dermatitis due to bleomycin intake  2021;29(2):102-104

Flagellate Dermatitis due to Bleomycin Intake

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