Photodermatology, Photoimmunology & Photomedicine
LETTER TO THE EDITOR
Solar burn reactivation reaction: an unusual side effect of methotrexate Emek Kocatürk1, Nagihan Köklü1, S¸ule Güngör1, Pelin Kuteyla Ülkümen1, Nilgün Bahçetepe1 & Selma S¸engiz Erhan2
1
Department of Dermatology, Okmeydanı Training and Research Hospital, Istanbul, Turkey. 2 Department of Pathology, Okmeydanı Training and Research Hospital, Istanbul, Turkey.
Correspondence: Dr Emek Kocatürk, MD, Department of Dermatology, Okmeydanı Training and Research Hospital, Nadiraga Sok. No: 25/9 Göztepe, 34730, I˙stanbul, Turkey. Tel: +00 90 216 565 43 08 Fax: +00 90 212 221 78 00 e-mail: [email protected]
Accepted for publication: 23 May 2014
Conflicts of interest: None declared.
To the Editor, Methotrexate (Mtx) is an immunosuppressive and antimitotic agent that terminates deoxyribonucleic acid (DNA) synthesis by inhibiting the enzyme dihydrofolate reductase. The spectrum of clinical usage and the side effects are quite common. Reactivation of radiation dermatitis, generalized maculopapular rash, stomatitis, and exacerbation of acne lesions can be associated with the use of Mtx (1). Phototoxicity is a direct tissue damage that is caused by phototoxic agents and UV light via inflammatory mediators (2). Sunburn reactivation is a rare and specific UV recall dermatitis that is seen in patients previously suffering from sunburn (3). This phenomenon is quite different from 338
other cytotoxic drug-induced radiation recall dermatitis. Low dose Mtx given to psoriasis patients does not appear to cause this recall reaction. This may be a time- and doserelated reaction (1). Some points will be emphasized in this paper to avoid this side effect. A 45-year-old male who was receiving Mtx treatment for psoriasis developed an erythematous, painful, and edematous rash on the chest, abdomen, and extremities. He went to the shore for swimming and sunbathing on Sunday and had a moderate erythema on sun-exposed areas. Three days after sunbathing, he took 16 tablets of Mtx (2.5 mg tablets, a total of 40 mg) by mistake, even though he was prescribed to take 10 mg a week. Twentyfour hours after receiving high-dose Mtx, the patient noticed burning and increased redness on his skin at sites where he had sun-induced erythema previously. The dermatologic examination revealed erythema on the sunexposed areas of his upper back, chest, arms, and legs. There was erythematous to violaceous and edematous plaques with hyperemia and pain in involved skin areas (Fig. 1a, b). Patient was hospitalized, and Mtx therapy is ceased. It was revealed from the patient’s history that he has been taking Mtx 40 mg/week since 6 weeks, and his psoriasis was in remission. Complete blood count and biochemical values were in normal range. Histopathological examination revealed epidermal spongiosis, intraepidermal apopitotic keratinocytes, and vesiculation, which was consistent with phototoxic reaction. Symptomatic treatment with wet dressings and antihistaminics resulted in a rapid resolution of the lesions. He was free of psoriasis lesions when he was discharged from the hospital but had recurrence after 6 weeks. Mtx is an antimitotic and immunosuppressive agent used for the treatment of cancer, psoriasis, and rheumatologic disorders. The well-known side effects include mucosal ulceration, hepatotoxicity, pulmonary fibrosis, myelosuppression, alopecia, and renal toxicity (1). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd doi:10.1111/phpp.12128
Letter to the Editor
a
b
Fig. 1. Sharply demarcated erythematous patches on sun-exposed areas in the (a) front and (b) back of the patient.
Mtx is reported to cause photosensitivity reactions in 5–6% of patients. Two major mechanisms of druginduced photosensitivity reactions are phototoxic and photoallergic responses. Clinically sharply demarcated erythematous and edematous lesions along with burning sensation are seen in the former, whereas vesicular and eczematous lesions resembling allergic contact dermatitis are seen in the latter (1, 3). The relationship between UV reactivation and Mtx was first reported by Vogler in 1965. A second case was described 4 years later by Möller, who made an experiment in an animal model system in which he applied Mtx and ultraviolet light simultaneously and concluded that this was not a real photosensitivity reaction (1). Due to the different designations in the literature and confusion in identification, the classification of these reactions is still unclear. As this reaction can be induced by UVA, UVB, or both (rarely x-rays), some authors propose that this reac-
tion can be called as photodermatitis reactivation reaction or photoreactivation reaction (1, 3). The pathogenesis of this phenomenon is not well understood. Korossy and Hood reported that increased DNA, RNA, and protein synthesis for epidermal regeneration after sunburn may be blocked by Mtx, and they also suggested that Mtx might inhibit mononuclear cell responses to ultraviolet (1, 3). In summary, Mtx-induced photodermatitis reactivation is a specific, idiosyncratic, and rare photosensitivity reaction. It cannot be prevented by folinic acid rescue and does not occur if Mtx is given simultaneously with UV radiation or if Mtx is given more than 5–7 days after exposure to UV radiation (2). Clinicians should be aware of this side effect especially during summer months, and Mtx treatment should be suspended for 1 week in patients with sunburn (1). Dermatologists should warn patients on Mtx therapy against sun exposure and should encourage use of sunscreens.
REFERENCES 1. Khan AJ, Marghoob AA, Prestia AE, Spector IJ. Methotrexate and the photodermatitis reactivation reaction: a case report and review of the literature. Cutis 2000; 66: 379–382. 2. Lugovic L, Situm M, Ozanic-Bulic S, Sjerobabski-Masnec I. Phototoxic and
photoallergic skin reactions. Coll Antropol 2007; 31: 63–67. 3. Basile FG, Creamer S. Docetaxel/ Cyclophosphamide-induced ultraviolet recall dermatitis. J Clin Oncol 2011; 29: e840–e841.
Photodermatol Photoimmunol Photomed 2014; 30: 338–339 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
339
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
LETTER TO THE EDITOR
Solar burn reactivation reaction: an unusual side effect of methotrexate Emek Kocatürk1, Nagihan Köklü1, S¸ule Güngör1, Pelin Kuteyla Ülkümen1, Nilgün Bahçetepe1 & Selma S¸engiz Erhan2
1
Department of Dermatology, Okmeydanı Training and Research Hospital, Istanbul, Turkey. 2 Department of Pathology, Okmeydanı Training and Research Hospital, Istanbul, Turkey.
Correspondence: Dr Emek Kocatürk, MD, Department of Dermatology, Okmeydanı Training and Research Hospital, Nadiraga Sok. No: 25/9 Göztepe, 34730, I˙stanbul, Turkey. Tel: +00 90 216 565 43 08 Fax: +00 90 212 221 78 00 e-mail: [email protected]
Accepted for publication: 23 May 2014
Conflicts of interest: None declared.
To the Editor, Methotrexate (Mtx) is an immunosuppressive and antimitotic agent that terminates deoxyribonucleic acid (DNA) synthesis by inhibiting the enzyme dihydrofolate reductase. The spectrum of clinical usage and the side effects are quite common. Reactivation of radiation dermatitis, generalized maculopapular rash, stomatitis, and exacerbation of acne lesions can be associated with the use of Mtx (1). Phototoxicity is a direct tissue damage that is caused by phototoxic agents and UV light via inflammatory mediators (2). Sunburn reactivation is a rare and specific UV recall dermatitis that is seen in patients previously suffering from sunburn (3). This phenomenon is quite different from 338
other cytotoxic drug-induced radiation recall dermatitis. Low dose Mtx given to psoriasis patients does not appear to cause this recall reaction. This may be a time- and doserelated reaction (1). Some points will be emphasized in this paper to avoid this side effect. A 45-year-old male who was receiving Mtx treatment for psoriasis developed an erythematous, painful, and edematous rash on the chest, abdomen, and extremities. He went to the shore for swimming and sunbathing on Sunday and had a moderate erythema on sun-exposed areas. Three days after sunbathing, he took 16 tablets of Mtx (2.5 mg tablets, a total of 40 mg) by mistake, even though he was prescribed to take 10 mg a week. Twentyfour hours after receiving high-dose Mtx, the patient noticed burning and increased redness on his skin at sites where he had sun-induced erythema previously. The dermatologic examination revealed erythema on the sunexposed areas of his upper back, chest, arms, and legs. There was erythematous to violaceous and edematous plaques with hyperemia and pain in involved skin areas (Fig. 1a, b). Patient was hospitalized, and Mtx therapy is ceased. It was revealed from the patient’s history that he has been taking Mtx 40 mg/week since 6 weeks, and his psoriasis was in remission. Complete blood count and biochemical values were in normal range. Histopathological examination revealed epidermal spongiosis, intraepidermal apopitotic keratinocytes, and vesiculation, which was consistent with phototoxic reaction. Symptomatic treatment with wet dressings and antihistaminics resulted in a rapid resolution of the lesions. He was free of psoriasis lesions when he was discharged from the hospital but had recurrence after 6 weeks. Mtx is an antimitotic and immunosuppressive agent used for the treatment of cancer, psoriasis, and rheumatologic disorders. The well-known side effects include mucosal ulceration, hepatotoxicity, pulmonary fibrosis, myelosuppression, alopecia, and renal toxicity (1). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd doi:10.1111/phpp.12128
Letter to the Editor
a
b
Fig. 1. Sharply demarcated erythematous patches on sun-exposed areas in the (a) front and (b) back of the patient.
Mtx is reported to cause photosensitivity reactions in 5–6% of patients. Two major mechanisms of druginduced photosensitivity reactions are phototoxic and photoallergic responses. Clinically sharply demarcated erythematous and edematous lesions along with burning sensation are seen in the former, whereas vesicular and eczematous lesions resembling allergic contact dermatitis are seen in the latter (1, 3). The relationship between UV reactivation and Mtx was first reported by Vogler in 1965. A second case was described 4 years later by Möller, who made an experiment in an animal model system in which he applied Mtx and ultraviolet light simultaneously and concluded that this was not a real photosensitivity reaction (1). Due to the different designations in the literature and confusion in identification, the classification of these reactions is still unclear. As this reaction can be induced by UVA, UVB, or both (rarely x-rays), some authors propose that this reac-
tion can be called as photodermatitis reactivation reaction or photoreactivation reaction (1, 3). The pathogenesis of this phenomenon is not well understood. Korossy and Hood reported that increased DNA, RNA, and protein synthesis for epidermal regeneration after sunburn may be blocked by Mtx, and they also suggested that Mtx might inhibit mononuclear cell responses to ultraviolet (1, 3). In summary, Mtx-induced photodermatitis reactivation is a specific, idiosyncratic, and rare photosensitivity reaction. It cannot be prevented by folinic acid rescue and does not occur if Mtx is given simultaneously with UV radiation or if Mtx is given more than 5–7 days after exposure to UV radiation (2). Clinicians should be aware of this side effect especially during summer months, and Mtx treatment should be suspended for 1 week in patients with sunburn (1). Dermatologists should warn patients on Mtx therapy against sun exposure and should encourage use of sunscreens.
REFERENCES 1. Khan AJ, Marghoob AA, Prestia AE, Spector IJ. Methotrexate and the photodermatitis reactivation reaction: a case report and review of the literature. Cutis 2000; 66: 379–382. 2. Lugovic L, Situm M, Ozanic-Bulic S, Sjerobabski-Masnec I. Phototoxic and
photoallergic skin reactions. Coll Antropol 2007; 31: 63–67. 3. Basile FG, Creamer S. Docetaxel/ Cyclophosphamide-induced ultraviolet recall dermatitis. J Clin Oncol 2011; 29: e840–e841.
Photodermatol Photoimmunol Photomed 2014; 30: 338–339 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
339
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
