Tricyclic antidepressant-induced photosensitivity; A case report and systematic review

Background/purpose: Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug reactions is essential.

Method: We reported a case of photo-distributed hyperpigmentation due to imipramine and carried out a systematic search of the related articles using the search terms "tricyclic antidepressants" or "tricyclic antidepressive agents", and "hyperpigmentation" or "photosensitivity disorder". Fifty non-duplicate citations were identified of which 28 articles which were independently assessed in full. The review was registered in PROSPERO, CRD42018107338.

Results: The remaining 25 articles met our inclusion criteria. Photo-distributed hyperpigmentation tricyclic antidepressant-induced photosensitivity reactions (TIPs) was the most common presentation. In 21 cases, this presented as an asymptomatic discolouration of exposed sites. Imipramine (81%), amitriptyline (9.5%), desipramine hydrochloride (4.8%) and mirtazapine (4.8%) were reported to be the culprit drugs. Nineteen were female with a mean age at presentation of 55 years. Mean duration from commencing the culprit drug until the development of discolouration was 10.4 years. Mean daily dose was 222.7 mg for imipramine. Histology was characteristic with golden-brown or brownish granules deposited in dermis. Staining for Masson-Fontana and MEL-5 was positive in all cases. Phototesting had not been done in cases prior to ours (negative 3 months after discontinuation of imipramine). Three further reports of suspected TIP presented with non-specific and eczematous eruption. The two presentations were reported along with systemic problems (thrombocytopenia and hepatic injury).

Conclusions: This systematic review highlights the characteristic features of exposed site hyperpigmentation of TCA-induced photosensitivity occurring after prolonged drug exposure in many cases.