Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. METHODS: This phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks. The primary end point was the percentage of participants achieving HS clinical response (HiSCR) at week 16. Safety, including treatment-emergent adverse events (TEAEs), was monitored throughout. RESULTS: Totals of 52, 47, 47, and 48 participants were assigned to brepocitinib, zimlovisertib, ropsacitinib, and placebo, respectively. At week 16, 28% were lost to follow-up and assumed to be nonresponders; HiSCR occurred in 33.3% (16/48) of participants receiving placebo and in 51.9% (27/52), 34.0% (16/47), and 37.0% (17/46) of those receiving brepocitinib, zimlovisertib, and ropsacitinib (difference in percentage points vs. placebo [90% confidence interval], 18.7 [2.7 to 34.6], 0.7 [−15.2 to 16.7], and 3.5 [−12.6 to 19.6]), respectively. TEAEs occurred more frequently with active treatment (brepocitinib, 30 [57.7%]; zimlovisertib, 26 [55.3%]; ropsacitinib, 29 [61.7%]; placebo, 23 [47.9%]). Most TEAEs (infections, skin disorders, and gastrointestinal symptoms) were mild; there were no deaths. CONCLUSIONS: Participants with moderate to severe HS treated with brepocitinib experienced greater clinical response, whereas those on zimlovisertib and ropsacitinib did not, compared with placebo. These results favor the JAK/STAT pathway as an immunologic target in HS and did not confirm a role for selective IRAK4 or TYK2 inhibition. These results should be confirmed in larger studies with longer follow-up. (Funded by Pfizer; ClinicalTrials.gov registration number, NCT04092452.)

Lichen planus associated with secukinumab treatment for plaque psoriasis.

Secukinumab and ixekizumab are IL17A inhibitors most commonly used to treat psoriasis. Common side effects include upper respiratory tract infections, injection site reactions, and mucocutaneous candidiasis. Recently, these medications have been reported to trigger lichen planus and lichenoid reactions have also been reported as an emerging side effect of biologics, especially tumor necrosis factor inhibitors. Herein, we report a patient with lichen planus that appeared after initiation of secukinumab for the treatment of psoriasis.

Granular Cell Tumor Imaging Using Optical Coherence Tomography.

BACKGROUND: Granular cell tumor (GCT) is a relatively uncommon tumor that may affect the skin. The tumor can develop anywhere on the body, although it is predominately seen in oral cavities and in the head and neck regions. Here, we present the results of optical coherence tomography (OCT) imaging of a large GCT located on the abdomen of a patient. We also present an analytical method to differentiate between healthy tissue and GCT tissues. MATERIALS AND METHODS: A multibeam, Fourier domain, swept source OCT was used for imaging. The OCT had a central wavelength of 1305 ± 15 nm and lateral and axial resolutions of 7.5 and 10 µm, respectively. Qualitative and quantitative analyses of the tumor and healthy skin are reported. RESULTS: Abrupt changes in architectures of the dermal and epidermal layers in the GCT lesion were observed. These architectural changes were not observed in healthy skin. DISCUSSION: To quantitatively differentiate healthy skin from tumor regions, an optical attenuation coefficient analysis based on single-scattering formulation was performed. The methodology introduced here could have the capability to delineate boundaries of a tumor prior to surgical excision.

Breast lesions with intractable pain in end-stage renal disease: calciphylaxis with chronic hypotensive dermatopathy related watershed breast lesions.

BACKGROUND: There are very few reports about end-stage renal disease (ESRD) patients with breast pains in the medical literature, posing a difficulty to understand their pathophysiology. CASE PRESENTATION: A 47-year-old African American female patient with ESRD on hemodialysis presented to the pain clinic with new-onset black maculopapular skin lesions on her breasts. These lesions started out as dark spots and then became necrosed, exposing the underlying tissue. The painful and tender lesions were located in a circumferential pattern around the bases of both breasts. She had stopped using breast supporting undergarments secondary to allodynia-hyperalgesia eliciting from necrotizing skin tissues. Her recent skin biopsy was inconclusive about ruling in or out the possibility of calciphylaxis. However, her past mammograms had showed calcium deposits in her breasts. Her other past medical history was significant for chronic hypotension with recently diagnosed legal blindness bilaterally. Her home medications included midodrine. The systolic blood pressures in either arm were consistently recorded in high 60s to low 70s during the interdialytic periods. She had multiple emergency room admissions secondary to persistent chronic hypotension; however the underlying pathophysiology for intractable but asymptomatic hypotension remained obscure. Over the course of the next 11 months her nonhealing breast lesions progressed and became infected. She developed septic shock due to infected lesions. Per her do-not-resuscitate requests, she died peacefully while under inhospital hospice care. CONCLUSION: Morbidity-mortality with calciphylaxis and chronic hypotension related tissue changes is high, and the breast lesions in ESRD patients require aggressive treatment for underlying inadequate oxygen delivery to these peripheral tissues.

Treatment of verrucae vulgaris and molluscum contagiosum with photodynamic therapy.

The use of 5-aminolevulinc acid photodynamic therapy in the treatment of recalcitrant verrucae vulgaris and in the treatment of recalcitrant molluscum contagiosum has been shown to substantially reduce the lesion count and severity. Clinical research published in the medical literature and personal experience of both of the authors support the use of 5-aminolevulinc acid photodynamic therapy in appropriate individuals with recalcitrant verrucae vulgaris and molluscum contagiosum lesions. This article reviews the medical literature and identifies the various lasers and lights sources used to treat these conditions.

Photodynamic therapy for molluscum contagiosum infection in HIV-coinfected patients: review of 6 patients.

Molluscum contagiosum, a viral disease of the skin, manifests as a smooth-surfaced, firm, and spherical papule with umbilication of the vertex. It commonly presents as multiple lesions, which may be extensive in immunocompromised patients, and may mimic cutaneous tumors in HIV co-infected patients. Infection usually persists for 6 months to 5 years before resolving naturally. Among immune-impaired persons with HIV infection is generally more persistent. To date, single and combination therapies for such patients have been unsatisfactory. Recent observations from a dermatology practice in which 6 patients with HIV and molluscum contagiosum were treated with 5-aminolevulinic acid (Levulan Kerastick) in conjunction with photodynamic therapy suggest clinical benefits; i.e., substantial reduction in lesional count and severity. Additional research is mandated.