Index Case
We first evaluated Patient 1, a 52-year-old female with a 30-year history of guttate psoriasis without psoriatic arthritis. Her psoriasis was generally well managed with topical therapy (clobetasol and hydrocortisone creams) and heliotherapy.
At age 43, Patient 1 was diagnosed with Durie-Salmon stage 3A IgG kappa MM, with genetic profiling showing trisomy 9 and 11, tetrasomy 15, and a t(14;20) translocation. She was found to have diffuse osteolytic lesions throughout the body, and subsequently underwent dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide (D-PACE) and bortezomib, thalidomide, and dexamethasone (VTD) chemotherapy treatment. Tandem autologous stem cell transplantation (ASCT) was performed, followed by a year of maintenance therapy with VTD and an additional year with dexamethasone, after which Patient 1 achieved a complete remission (CR) approximately 1 year after initial MM diagnosis. Dexamethasone maintenance was started immediately for 1 year, and the patient remained in stringent CR with consistent monitoring.
However, at age 48, despite no evidence of active myeloma on imaging, bone marrow biopsy showed 5% presence of plasma cells, which is at the borderline level for MM recurrence. Osteoporosis-preventing infusions were subsequently administered every 3 months and markers were closely tracked for the following 4 years; M-protein and serum markers (e.g., albumin, creatinine) remained stable, and no acute findings or evidence of active disease progression was noted.
At age 52, Patient 1 was noted to have a sharp increase in MM biomarkers, including kappa and urine paraprotein. She also developed a psoriatic flare with lesions noted on the posterior neck, right lower abdomen, and chest. There was mild scaling and induration of psoriatic lesions, and she was prescribed topical creams and started on ixekizumab therapy. Ixekizumab was selected based on its established efficacy in psoriasis and studies suggesting a pathogenic role for IL-17 in the progression of MM [6]. Twelve days after the first loading dose injection of ixekizumab, the patient developed urticarial wheals appearing on the abdomen, trunk, and head and neck. This eruption resolved after a 1-week course of prednisone 40 mg and fexofenadine. In the patient’s first MM biomarker assessment after the start of ixekizumab, drops in her kappa:lambda ratio, kappa free light chain, and M-protein levels were observed (Fig. 1). A further decrease in these clinical markers was found in a second assessment 2 weeks later. Thereafter, these markers fluctuated in a range below the highest peak. The patient reported minimal efficacy of ixekizumab for her psoriasis and thus decided to discontinue use after 2 months.
Case Series Using Digital Crowdsourcing
To further understand clinical features and treatment responses among patients with both MM and psoriasis, health data crowdsourced on HealthTree were used. A total of 1505 HealthTree enrollees had verified physician diagnoses of myeloma, and psoriasis was present in 4.9% (n = 73) of this population. Surprisingly, psoriasis was one of the most frequent co-morbidities found in the HealthTree myeloma patient population, alongside conditions such as osteopenia, inflammatory bowel disease, and gout. Our questionnaire (Table S1) was administered to HealthTree patients (n = 73) with verified health records showing diagnosis of both psoriasis and MM. The questionnaire yielded 18 complete responses, including from Patient 1 described above. Findings pertaining to psoriasis are summarized in Table 1, while myeloma features are summarized in Table 2. Characteristics evaluated in the questionnaire include gender, current age, age of diagnosis, psoriasis type, psoriasis treatment history, myeloma type and genetic features, and myeloma association with bone damage, hypercalcemia, or osteopenia.
Table 1 Psoriasis characteristics among survey respondents Table 2 Myeloma characteristics among survey respondents Among respondents, the mean age of psoriasis diagnosis was 35.9 (SD 8.2), while the mean age of myeloma diagnosis was 57.1 (SD 8.6). In most patients, diagnosis of psoriasis occurred well before diagnosis of myeloma (mean difference of 21.2 years). Seven out of 18 respondents identified as female (38.9%), and the most common type of psoriasis diagnosed was plaque (44.4%), followed by palm/sole (16.7%), guttate (11.1%), and inverse (5.6%). Two patients (11.1%) indicated that their psoriasis treatment (topical steroids) had improved their MM, and 33.3% indicated they were uncertain. No patients reported that psoriasis treatment had negatively influenced myeloma progression, and 50% were uncertain. Psoriasis treatments were most commonly topical steroids, followed by tar, phototherapy, heliotherapy, and antifungal or immunosuppressive agents.
Myeloma diagnoses included MM (72.2%), smoldering myeloma (33.3%), and monoclonal gammopathy of undetermined significance (27.8%)—several patients were diagnosed with multiple subtypes. The types of myeloma represented included IgG kappa (50.0%), IgA kappa (11.1%), IgA lambda (11.1%), and IgM lambda (5.6%) as well as 22.2% uncertain. Among respondents, 29.4% reported bone damage (e.g., fracture), 16.7% reported hypercalcemia, and 33.3% reported osteopenia.
Out of all respondents, Patients 1, 6, 10, and 16 had received treatment with systemic therapies: ixekizumab (anti-IL17), apremilast (anti-PDE4), ustekinumab (anti-IL12/IL23), and certolizumab (anti-TNF), respectively. These four patients affirmed that systemic psoriasis treatment did not worsen their initial MM, with two patients demonstrating temporary or unclear improvement in MM control following systemic therapy. No other differences specific to this subgroup of patients were found.
Consent for publication was received from the index patient; the digitally crowdsourced patient data were determined to be exempt by the Western Institutional Review Board (IRB) under exemption code 45 CFR § 46.104(d)(2). This case report was conducted according to the principles of good clinical practice guidelines ICH GCP and according to the ethical principles of the Declaration of Helsinki.