Discussion
Lentigines are the most basic form of melanocytic proliferation, on a spectrum that progresses to junctional, compound, and dermal naevi. Inflammation or immunosuppression can induce melanocyte hyperplasia. Cytotoxic agents may also induce lentigines via modulation of tumour-specific lymphocytes. 4 Eruptive lentigines have been described in the context of psoriasis, atopic dermatitis, and drug eruptions, as well as secondary to both psoralen and ultraviolet A (PUVA) and ultraviolet B (UVB) phototherapy. Topical tacrolimus and topical immunotherapy with dibutyl squaric acid have also been associated with lentigines. Drugs implicated in eruptive lentiginosis include immunomodulatory therapy such as methotrexate, azathioprine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, secukimumab, and ixekizumab, and cancer chemotherapy.
Acral lentiginosis is characterised by eruptive lentigines limited to the hands and feet. The predilection for acral sites may occur due to a combination of altered immunosurveillance and elevated local trophic factors present in acral skin. 6 Exposure to ultraviolet radiation may facilitate their development. Eruptive acral lentiginosis has been reported following chemotherapy for ALL in children 7, and following treatment with capecitabine4 and tegafur 8 (both prodrugs of 5-fluorouracil).
There are obvious difficulties in ascertaining the culprit drug for lentiginosis when multiple cytotoxic and immunosuppressive drugs are administered concomitantly as a part of a chemotherapeutic protocol. Anecdotally, we have also noted several cases of eruptive acral lentiginosis in patients treated with high dose cytarabine for acute myeloid leukaemia (C Ryan, personal observation). Development of lentigines may depend on a complex milieu of cancer, immunosuppression, cytotoxic drug therapy, and UV exposure.
Generalised eruptive naevi with subsequent development of dysplastic naevi and melanoma in situ have been reported following chemotherapy9, highlighting the importance of continued clinical observation.