Efficacy of JAK inhibitors in the treatment of psoriasiform atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexisting of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-IL-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed JAK inhibitors (JAKi) as a viable alternative, even in the first line, in patients with different clinical phenotypes of AD, including psoriasiform AD. A retrospective analysis of patients in our dermatology clinic with moderate-severe AD and treated with JAKi was performed. Among the 192 overall patients, 21 had psoriasiform AD. EASI, p-NRS and DLQI were the severity scores considered and their reduction was observed in all 21 patients at weeks 4, 16 and 24 of treatment. At week 16 the percentage of patients achieving EASI-75 and EASI-90 was 80.95% and 66.67%, respectively. While at week 24 95.23% of patients achieved EASI-75 and 85.71% obtained EASI-90. No adverse event lead to treatment interruption. This study confirmed the clinical effectiveness of JAKi treatment in adult patients with moderate-to-severe psoriasiform AD, with a good safety profile. These drugs are proposed as the first choice for the treatment of this form of AD, although further studies with larger cohorts are required.

Eczematous drug eruption in patients with psoriasis under anti-interleukin-17A: does interleukin-22 play a key role?

BACKGROUND: Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. To date, EDE has been described in patients treated with anti-interleukin (IL)-17A monoclonal antibodies with a prevalence of 2.2%-12.1%. AIM: To describe the clinical and histological features and the skin cytokine milieu in patients with EDE induced by anti-IL-17A biologics. METHODS: This was a prospective study, enrolling patients with psoriasis who developed EDE during treatment with two anti-IL-17 biologics, ixekizumab and secukinumab, from June 2019 to April 2021. Skin biopsies were taken from all patients: a 5-mm lesional biopsy (LB) and a 3-mm nonlesional biopsy (NLB). The LB sample was split into two parts, one for histological examination and the other for cytokine profile evaluation. RESULTS: During the study period, treatment with an anti-IL-17A drug was given to 289 patients of whom 8 (2.8%) developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all eight patients. Cytokine gene expression showed a predominance of T helper (Th)2/Th22 cytokines in EDE lesions with a large increase in IL-4, IL-22 and S100A7 levels in both LB and NLB samples compared with healthy skin. IL-4, IL-22 and S100A7 were significantly higher in LB compared with NLB samples. IL-26 levels were also significantly increased in both LB and NLB compared with healthy skin, whereas low levels of IL-23A were found in both LB and NLB. CONCLUSION: Eczematous drug eruption skin lesions have mainly Th2/Th22 features, with IL-22 playing a major role in their pathogenesis. EDE seems to be the result of an imbalance towards a Th2/Th22 response, secondary to the blockade of IL-17A activity.

Tinea pedis in a child: How reflectance confocal microscopy can help in diagnosis of dermatophytosis.

A 7-year-old girl presented with a hyperkeratotic scale on the plantar surface of her left foot. A microscopic potassium hydroxide examination was performed and negative. Reflectance confocal microscopy was performed showing fungal hyphae and an inflammatory infiltrate confirming a diagnosis of tinea pedis.

Is there any association between psoriasis, psoriatic arthritis and thyroid autoimmunity?

BACKGROUND: Autoimmune diseases share a significant part of their genetic background and tend to coexist in the same patient. Some studies have investigated the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with conflicting results. This study aimed to investigate the prevalence of autoimmune thyroiditis in psoriatic patients with (PsA) or without (PsC) joint involvement. METHODS: 208 patients with psoriasis and/or PsA were recruited. These patients were divided into two groups: psoriasis patients (without PsA) (PsC group: 100 patients; mean age of 50.1 ± 11.7 years) and subjects with psoriasis and psoriatic arthritis (PsA group: 108 subjects: mean age of 39.8 ± 10.8 years). Assessment of psoriasis severity was conducted using the Psoriasis Area and Severity Index (PASI) score. The diagnosis of psoriatic arthritis was made according to CASPAR criteria. All patients had thyroid evaluation through evaluation of thyroid function, thyroperoxidase antibodies and thyroid ultrasound examination. RESULTS: A statistically significant difference was found between the prevalence of autoimmune thyroiditis in the PsA group than the PsC group (25.9 vs 9.0 %; P = 0.018) with higher trends to hypothyroidism in the PsA group compared to the PsC group (13.9% vs 2.0%, P = 0.0018). CONCLUSIONS: The higher prevalence of autoimmune thyroiditis in the PsA group may be due to an immune dysfunction pathway in patients with psoriatic arthritis with a higher risk to develop other autoimmune diseases. This evidence confirms that psoriatic arthritis is an autoimmune disease with an overactive immune system that can involve multiple organs. Thyroid function evaluation should be part of the clinical and laboratory examination of patients with psoriatic arthritis.

Cutaneous localization of plasmablastic multiple myeloma with heterotopic expression of CD3 and CD4: Skin involvement revealing systemic disease.

Plasmablastic multiple myeloma is an uncommon morphological variant of multiple myeloma with aggressive clinical course and poor outcome. Its differential diagnosis includes plasmablastic lymphoma, a variant of diffuse large B-cell lymphoma with frequent extranodal presentation, which usually affects immunosuppressed patients and is virtually indistinguishable from plasmablastic multiple myeloma on the basis of histology solely. Differential diagnosis relies on close clinical-pathological correlation. Herein, the authors report a case of aggressive multiple myeloma occurring in a 48-year-old patient with pure plasmablastic morphology, expression of T-cell markers CD3 and CD4, and cutaneous involvement as first presenting sign. Heterotopic expression of T-cell markers has been described in literature for both plasmablastic multiple myeloma and plasmablastic lymphoma. The causative mechanisms underlying this aberrant phenotype have not yet been elucidated; nevertheless the possibility of this rare finding should be considered to avoid misinterpretations. Remarkably, despite occurring rarely, cutaneous involvement could be observed at an early stage or even be the first manifestation of disease in particularly aggressive forms of myeloma. As a consequence, the presence of cutaneous lesions should not favor a straightforward diagnosis of plasmablastic lymphoma. The importance of a correct differential diagnosis lies in its therapeutical implications.

A case of erythrodermic psoriasis successfully treated with ixekizumab.

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. International guidelines on EP treatment are lacking, with most of the biologic drugs being used basing on case reports or small case series. Ixekizumab, a fully human anti-interleukin (IL)-17A monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. However, two studies conducted on eight Japanese EP patients have showed ixekizumab as an efficacious and well tolerated therapy up to 24 and 52 weeks, respectively. To date, no case reports on Caucasian patients have been described. We report the case of a 66-year-old Caucasian female with EP successfully treated with ixekizumab, reaching PASI 100 after only 6 weeks of therapy and still maintaining this response at week 24. Our case report suggests ixekizumab as a highly efficacious treatment in EP, presenting also a very rapid action which leads to complete resolution of the disease after 6 weeks. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of the new biologics in EP.

Hypersensitivity reaction to certolizumab pegol in a patient affected by psoriatic arthritis.

The pathogenic mechanism of hypersensitivity reactions (HSRs) to monoclonal antibodies is not fully understood. HSRs can occur after the first exposure or multiple exposures and include acute infusion reactions induced by cytokine release, besides Type I, Type III, and Type IV reactions.). We reported a case of anaphylactic reaction to certolizumab pegol in a patient affected by psoriatic arthritis and a possible management of this condition.

A 15-year retrospective study on the prevalence of onychomycosis in psoriatic vs non-psoriatic patients: A new European shift from dermatophytes towards yeast.

Because of their similar clinical presentation, discrimination between nail psoriasis and onychomycosis often is difficult. We aim to investigate the actual frequency of onychomycosis in psoriatic patients and to compare it between psoriatic and non-psoriatic patients. This retrospective study included a total of 9281 patients, referring to our Mycology Laboratory from September 2003 to May 2018. The patients are divided into two groups: PsoGroup (patients with psoriasis) and non-PsoGroup (non-psoriatic patient). Direct microscopic examination with 20% KOH and culture was carried out in both groups. In PsoGroup (711 patients, 59.50% female, 40.50% male, median age of 52.22 ± 15.01), the prevalence of onychomycosis was 49.08%. On the other hand, in non-PsoGroup (8570 patients (71.65% female, 28.35% male, median age of 48.51 ± 19.31 years), the prevalence of onychomycosis was 51.30%. There was no statistically significant difference between the prevalence of onychomycosis in PsoGroup 49.08% (349/711) compared to 51.30% (4397/8570) of non-PsoGroup (P = 0.2578). However, yeasts were significantly more prevalent in non-psoriatic than in psoriatic patients (P = 0.0144.). In our Mycological Laboratory, we observed a similar prevalence of onychomycosis in psoriatic patients and non-psoriatic patients. However, the spectrum of fungal species isolated was different from each other, with a higher prevalence of yeasts in non-PsoGroup that reflect a recent oriental trends.