To the Editor:
Lenalidomide is a thalidomide analogue used to treat various hematologic malignancies, including non-Hodgkin lymphoma, myelodysplastic syndrome, and multiple myeloma (MM).1 Lenalidomide is referred to as a degrader therapeutic because it induces targeted protein degradation of disease-relevant proteins (eg, Ikaros family zinc finger protein 1 [IKZF1], Ikaros family zinc finger protein 3 [IKZF3], and casein kinase I isoform-α [CK1α]) as its primary mechanism of action.1,2 Although cutaneous adverse events are relatively common among thalidomide analogues, the morphologic and histopathologic descriptions of these drug eruptions have not been fully elucidated.3,4 We report a novel pityriasiform drug eruption followed by a clinical eruption suggestive of blaschkitis in a patient with MM who was being treated with lenalidomide.
A 76-year-old man presented to the dermatology clinic with a progressive, mildly pruritic eruption on the chest and axillae of 1 year’s duration. He had a medical history of chronic hepatitis B, malignant carcinoid tumor of the colon, prostate cancer, and MM. The eruption emerged 1 to 2 weeks after the patient started oral lenalidomide 10 mg/d and oral dexamethasone40 mg/wk following autologous stem cell transplantation for MM. The patient had not received any other therapy for MM.
Physical examination revealed multiple erythematous, hyperpigmented, scaly papules and plaques on the lateral chest and within the axillae (Figure 1). A skin biopsy from the left axilla demonstrated a mild lichenoid and perivascular lymphocytic infiltrate with scattered eosinophils, neutrophils, and extravasated erythrocytes. The overlying epidermis showed spongiosis with parakeratosis in addition to lymphocytic exocytosis (Figure 2). No fungal organisms were highlighted on periodic acid–Schiff staining. After this evaluation, we recommended that the patient discontinue lenalidomide and start taking a topical over-the-counter corticosteroid for 2 weeks. Over time, he noted marked improvement in the eruption and associated pruritus.
FIGURE 1. Multiple erythematous, hyperpigmented, pityriasiform papules and plaques within the axillae.
After a drug holiday of 2 months, the patient resumed a maintenance dosage of oral lenalidomide 10 mg/d. Four or 5 days after restarting lenalidomide, a pruritic eruption appeared that involved the axillae and the left lower abdomen, circling around to the left lower back. The axillary eruption resolved with a topical over-the-counter corticosteroid; the abdominal eruption persisted.
FIGURE 2. A and B, A biopsy specimen of the left axilla demonstrated a mild lichenoid and perivascular lymphocytic infiltrate containing scattered eosinophils, neutrophils, and a few extravasated erythrocytes. The overlying epidermis was spongiotic with parakeratosis and lymphocytic exocytosis (H&E, original magnifications ×100 and ×200).
At the 3-month follow-up visit, physical examination revealed erythematous macules and papules that coalesced over a salmon-colored base along the lines of Blaschko extending from the left lower abdominal quadrant, crossing the left flank, and continuing to the left lower back without crossing the midline (Figure 3).
FIGURE 3. A and B, At a 3-month follow-up visit, erythematous macules and papules coalesced over a salmon-colored base along the lines of Blaschko extending from the left lower abdominal quadrant, crossing the left flank, and continuing to the left lower back without crossing the midline.
We recommended that the patient continue treatment through this eruption; he was instructed to apply a corticosteroid cream and resume lenalidomide at the maintenance dosage. A month later, he reported that the eruption and associated pruritus resolved with the corticosteroid cream and resumption of the maintenance dose of lenalidomide. The patient noted no further spread of the eruption.
Cutaneous adverse events are common following lenalidomide. In prior trials, the overall incidence of any-grade rash following lenalidomide exposure was 22% to 33%.5 A meta-analysis of 10 trials determined the overall incidence of all-grade and high-grade cutaneous adverse events after exposure to lenalidomide was 27.2% and 3.6%, respectively.6 Our case represents a pityriasiform eruption due to lenalidomide followed by a secondary eruption suggestive of blaschkitis.