Keratoderma-Like T-Cell Dyscrasia: A Case Report

The term “dyscrasia” has undergone a semantic shift within the field of dermatopathology. Historically, it denoted an abnormal mixture, often associated with disease states [1, 2]. Presently, its usage is primarily confined to the interpretation of laboratory findings that reveal a dominant T-cell clone [2]. A spectrum of cutaneous T-cell lymphocytic infiltrates (CTLIs) exists, defined by clinical presentation, microscopic features, phenotypic characteristics, and molecular signatures. These entities are collectively recognized as cutaneous T-cell dyscrasias (CTCDs) [3, 4]. CTCDs encompass a heterogeneous group of persistent, typically epitheliotropic, clonal T-cell infiltrates with a low propensity for progression to mycosis fungoides (MF) [5]. Similar to MF, CTCDs exhibit low-grade lymphoid atypia and phenotypic aberrations [6]. These aberrations include a reduction in the expression of specific pan-T-cell markers, most notably a significant decrease in CD62L and a less pronounced decrease in CD7 [7]. A distinguishing feature of CTCDs, compared to MF, is the presence of atypical intraepidermal lymphoid cells demonstrating a significant loss of CD5 or a double-negative phenotype (CD4− and CD8−). However, cases lacking sufficient cytologic atypia with CD7 loss can pose diagnostic challenges [8].

Several factors, including exposure to immune agents and infectious triggers, have been implicated in the development of CTLIs. However, the precise etiology remains elusive. Studies have reported an association between specific drug classes, such as antihistamines, benzodiazepines, and antidepressants, and the occurrence of reversible T-cell dyscrasia [5, 9]. Statins, a type of lipid-lowering agent, have been identified as the culprit medication in 6 documented cases of epidermotropic T-cell dyscrasia (ETD), with 4 of these cases presenting as keratoderma-like T-cell dyscrasia [5, 8].

Medical history: A patient with a history of type 2 diabetes mellitus, dyslipidemia, and hypertension was referred to dermatology for a 1-month pruritic, scaly eruption of the palms and soles unresponsive to topical steroids. Her medications included lisinopril, metformin, atorvastatin, calcium carbonate, and vitamin D. Examination revealed well-defined, irregularly shaped erythematous and scaly plaques on the palms and soles without nail involvement (Fig. 1). Laboratory investigation including complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein, and lactate dehydrogenase yielded normal results. Histopathological examination of the right sole punch biopsy specimen showed compact orthokeratosis and mild superficial perivascular lymphocyte infiltrate with focal exocytosis predominantly at the basal layer, and mild lymphocytic cytologic atypia including nuclear enlargement, hyperchromasia and irregular nuclear contour (Fig. 2a, b). Immunophenotyping studies showed a predominance of CD3-positive T cells with a CD4 to CD8 ratio of 1:1 and a preserved but decreased CD7 expression. The findings of palmoplantar keratoderma, low-grade lymphoid atypia, basilar lymphocyte exocytosis, and the phenotypic profile illustrated by a decline in CD7 expression collectively supported the diagnosis of keratoderma-like T-cell dyscrasia. Two weeks following atorvastatin disconsolation and the use of mid-potency topical steroids, the patient reported an 80% improvement in pruritus and reduced erythema and scaling of the palms and soles within 2 weeks. At the 6-month follow-up, complete resolution of the keratoderma and pruritus was observed (Fig. 3).

ETD is characterized by scaly erythematous plaques on the palms and/or soles, with histopathological findings of atypical epidermotropic T-cell proliferation, low-grade cerebriform lymphoid atypia, and a characteristic immunophenotype [8]. This phenotype includes a reduction in the expression of pan-T-cell markers CD7 and CD62L.

Magro and Nguyen [8] reported a series of thirteen ETD cases, four of which presented with features suggestive of statin-induced keratoderma-like T-cell dyscrasia. Statin discontinuation led to complete regression of the eruption and pruritus in 2 patients, and partial resolution (eruption resolved, pruritus persisted) in one. However, the fourth case demonstrated persistent palmar keratoderma despite statin withdrawal and subsequent azathioprine treatment. Notably, no clear temporal association between medication initiation and lesion onset was observed. Margo et al. [10] described a separate case series of 15 patients with drug-induced T-cell dyscrasia, two of which were statin-related. Histopathological features included a lymphoid infiltrate with cytologic atypia characterized by nuclear hyperchromasia, cerebriform contours, and condensed chromatin. Immunophenotyping revealed negative CD7 and/or CD62L expression with T-cell clonality and variable CD30 positivity, resembling findings in cutaneous T-cell lymphoma. However, unlike lymphoma, these drug-induced eruptions displayed complete or significant improvement upon drug discontinuation. Based on these observations, Margo et al. proposed the term “drug-induced reversible lymphoid dyscrasia” for this entity [10].

CTCD typically presents a challenging clinical course, characterized by recalcitrance and progression despite treatment [1]. However, a distinct subset of CTCD exhibits reversibility, classified as drug-induced reversible lymphoid dyscrasia [2]. These cases demonstrate atypical cutaneous T-cell lymphoid hyperplasia that resolves upon drug cessation [2]. A comprehensive medication history is crucial in diagnosing drug-induced reversible lymphoid dyscrasia as withdrawal of the causative agent is often associated with complete resolution of the cutaneous eruption [2]. Statins have been implicated in several cases of ETD, with four out of six reported cases presenting as keratoderma-like T-cell dyscrasia [3]. Notably, statin discontinuation led to the resolution of the cutaneous eruption and pruritus in most of these cases [3].

Beyond statins, other medications have also been linked to drug-induced reversible lymphoid dyscrasia. A recent report in JAMA Dermatology identified dupilumab, a biologic medication used for various inflammatory conditions, as a potential inducer of lymphoid hyperplasia [11]. Additionally, hydrochlorothiazide, a commonly prescribed diuretic, has been reported to cause a similar lymphoid response [12]. This growing list of medications underscores the importance of considering drug-induced reversible lymphoid dyscrasia in individuals presenting with atypical cutaneous lymphoid infiltrates [1].

Therefore, we advocate for a detailed medication history in all patients presenting with atypical cutaneous lymphoid infiltrates. Drug-induced reversible lymphoid dyscrasia should be considered in individuals taking medications known to induce lymphoid atypia as prompt drug withdrawal can lead to significant clinical improvement. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000541258).

This study protocol was reviewed ethical approval was given by the Saudi Arabia National Committee of Bioethics Accreditation Number (H-01-R-069) (attached file titled patient IRB). Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images (attached file titled patient consent).

The authors have no conflicts of interest to declare.

No specific funding was received for this work. The authors declare that all resources used in this case report were obtained through the standard departmental resources available at Security Forces Hospital Riyadh, which is a governmental hospital providing free healthcare to Saudi citizens.

A.S. and S.A.H. identified the patient’s case as a potential candidate for a case report; collected all relevant clinical data including patient history, physical examination findings, and treatment course; conducted a comprehensive literature review on cutaneous T-cell dyscrasia and statin-induced adverse effects; drafted the initial manuscript; and incorporated revisions based on feedback from co-authors. T.J.A.-Z. performed essential diagnostic evaluations to characterize the underlying pathology, that included histological examination of the skin biopsy to assess tissue morphology and immunophenotyping studies to identify the type and activation state of infiltrating lymphocytes; analyzed the findings in the context of the clinical presentation and correlated them with potential diagnoses, particularly focusing on features suggestive of CTCD; and provided detailed reports of their respective analyses for inclusion in the case report. R.A. supervised the management of the patient throughout the course of their care; provided mentorship and guidance to the first author during case identification, data collection, and manuscript writing; reviewed and critically revised all drafts of the manuscript, ensuring scientific accuracy and clarity; and provided final approval for submission of the manuscript.

The data underlying the findings of this case report are presented within the article. All cited references are publicly available as detailed in the reference list.