Drug‐induced cutaneous pseudolymphoma: A systematic review of the literature

Abstract

Drug‐induced cutaneous pseudolymphoma (CPL) is a common form of pseudolymphoma and there are numerous drugs associated with it. In this study, we performed a systematic review of the literature by searching PubMed/Medline and Embase databases to determine the most common drugs responsible for CPL and to define the demographic, clinical, histopathological and immunopathological characteristics of patients (updated on 30 December 2020). From 883 initially found articles, 56 studies (89 reported cases) were included. The mean age of patients was 54.4 ± 17.7 (ranging 8–86) years, and 46 (51.7%) were men. The median time interval between drug intake and CPL occurrence was 120 days (range 1–7300 days). The shortest median time interval between taking the drug and the onset of the disease was observed among patients taking antidepressants (60 days) (range 7–540) and the longest median time interval was observed in individuals using immunomodulators (300 days) (range 3–7300). The most‐reported drug categories causing CPL were anti‐hypertensives (17.9%), anticonvulsants (14.6%), monoclonal antibodies (13.4%) and antidepressants (11.2%). Moreover, the most common drugs were phenytoin (6.7%), amlodipine (5.6%), fluoxetine (5.6%) and carbamazepine (4.4%). Histopathological evaluation of 76 cases revealed 62 (81.5%) reports of T‐cell infiltrations. Furthermore, positive reports of CD4 (94.0%), CD8 (93.0%) and CD30 (87.5%) were noted. The lowest prevalence of CD30‐positive reports was observed among monoclonal antibodies. In conclusion, anti‐hypertensives, anti‐convulsants, monoclonal antibodies and anti‐depressants are the most common drugs responsible for CPL. It mostly presents in middle‐aged patients with almost no gender difference as pruritic papules, nodules and plaques.

Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis

“…The most common drugs associated with these CPLs were antihypertensive medications, anticonvulsants, monoclonal antibodies, and antidepressants, which were only used by 2 of the 11 patients in the present study. In 12 of 89 patients with CPL, a monoclonal antibody triggered the skin reaction (eg, infliximab, adalimumab, secukinumab), of which 5 patients had a dysregulated CD4:CD8 ratio . Because dupilumab is a monoclonal antibody, though with a different therapeutic mode of action, these drug-induced CPLs strengthen our findings on dupilumab-associated LRs and therefore it might be a subtype of CPLs.…”

“…In patients with LR, both clinical and histopathologic presentation showed several comparable findings with cutaneous drug reactions (ie, [generalized] maculopapular erythema, a perivascular [atypical] lymphoid infiltrate, CD30 expression). Moreover, Etesami et al reported on 89 cases in which drug-induced cutaneous pseudolymphomas (CPL) were found. In these patients (epi)dermal lymphoid infiltrates were found together with CD30 expression in 87.5% of the patients.…”

Cutaneous Reactive Lymphoid Proliferation Arising in the Setting of Concomitant Antidepressant and Antihypertensive Therapy

“…The time between exposure and onset can vary from days to months or even years, with antidepressants having a shorter median time to onset [ 5 ]. Our patient was taking both vortioxetine and lisinopril when the lesion presented, which could be a potential etiology.…”

“…Over a quarter of CRLP cases are caused by drug exposure [ 3 ]. Common causes of drug-induced CRLP are anticonvulsants, antidepressants, antihypertensives, and monoclonal antibodies [ 4 - 5 ]. The most frequent presentation is a solitary papule, nodule, or plaque, but others include multiple or disseminated lesions and even erythroderma [ 2 , 6 ].…”

CD30 in Cutaneous Pathology

“…Inflammatory drug eruptions have been sometimes reported to contain a large amount of CD30-positive cells. 88–93 Mainly antiepileptic drugs have been reported to have such findings. 79 Some of these infiltrates have shown an intralymphatic distribution, mimicking an intravascular lymphoma.…”