Pyruvate kinase M2 mediates IL-17 signaling in keratinocytes driving psoriatic skin inflammation.

Psoriasis is an inflammatory skin disease characterized by keratinocyte proliferation and inflammatory cell infiltration induced by IL-17. However, the molecular mechanism through which IL-17 signaling in keratinocytes triggers skin inflammation remains not fully understood. Pyruvate kinase M2 (PKM2), a glycolytic enzyme, has been shown to have non-metabolic functions. Here, we report that PKM2 mediates IL-17A signaling in keratinocytes triggering skin psoriatic inflammation. We find high expression of PKM2 in the epidermis of psoriatic patients and mice undergoing psoriasis models. Specific depletion of PKM2 in keratinocytes attenuates the development of experimental psoriasis by reducing the production of pro-inflammatory mediators. Mechanistically, PKM2 forms a complex with Act1 and TRAF6 regulating NF-κB transcriptional signaling downstream of the IL-17 receptor. As IL-17 also induces PKM2 expression in keratinocytes, our findings reveal a sustained signaling circuit critical for the psoriasis-driving effects of IL-17A, suggesting that PKM2 is a potential therapeutic target for psoriasis.

Case Report: Cannabidiol-Induced Skin Rash: A Case Series and Key Recommendations.

Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.

Metabolic syndrome and psoriatic arthritis among patients with psoriasis vulgaris: Quality of life and prevalence.

Interest has increased in comorbidities associated with psoriasis and their effects on health-related quality of life (HRQoL). This study aimed to evaluate the prevalence of metabolic syndrome (MetS) and psoriatic arthritis (PsA) and to investigate HRQoL and the prevalence of hypertension, type 2 diabetes mellitus (T2DM), obesity and dyslipidemia. In a cross-sectional design, patients diagnosed with plaque psoriasis answered an interview and standardized questionnaires (Dermatology Life Quality Index questionnaire [DLQI], 36-Item Short Form Health Survey [SF-36] and EuroQol Five-Dimension Questionnaire Three-Level version [EQ-5D-3L]). Physical examination and several tests to assess desired outcomes were performed by a dermatologist and a rheumatologist during three visits. The prevalence of MetS and PsA was 50.0% and 41.8%, respectively. Dyslipidemia was the most prevalent (74.5%) secondary comorbidity, followed by hypertension (61.8%), obesity (52.5%) and T2DM (30.9%). The mean (standard deviation) DLQI score was 6.5 (6.9), and mean physical and mental SF-36 measures were 45.2 (10.4) and 45.5 (12.3), respectively, and for EQ-5D-3L, mean utility index and EQ-VAS scores were 0.68 (0.27) and 72.7 (19.7), respectively. PsA and MetS are important comorbidities; a reduced HRQoL is noted among plaque psoriasis patients with these comorbidities, emphasizing the relevance of diagnosis and treatment beyond the care of skin lesions.

HLA-C and TNF gene polymorphisms are associated with psoriasis in Brazilian patients.

BACKGROUND: Polymorphisms at the human leukocyte antigens (HLA-C) and tumor necrosis factor (TNF) genes have been associated with susceptibility to psoriasis in several worldwide populations. In this study, HLA-C and TNF (-238/-308) polymorphisms were performed in 125 Brazilian patients and 202 healthy controls. METHODS: HLA-C and TNF promoter region alleles were typed by polymerase chain reaction using sequence-specific primer-polymerase chain reaction. RESULTS: The presence of HLA-C*06 was associated with psoriasis onset, particularly in younger patients, being more frequent for patients with disease onset before the age of 20 years (P = 0.03), 25 years (P = 0.01), or 30 years (P = 0.03). No association between HLA-C*06 and psoriasis was observed for patients older than 35 years. Susceptibility to psoriatic arthritis was associated with the TNF -238 G/A genotype (P = 0.02). The TNF -308A allele was overrepresented in patients (P = 0.0061), and the TNF -308 G/A genotype was increased in generalized forms (erythrodermic and generalized pustular psoriasis) compared to plaque psoriasis (P < 0.001). The TNF -238A/HLA-C*06 haplotype was overrepresented in patients (P = 0.025), while the TNF -238G/HLA-C*15 haplotype was increased in controls (P = 0.037). CONCLUSIONS: The strong association of HLA-C*06 allele with disease susceptibility, particularly in early onset psoriasis, indicates that younger ages could be considered to stratify psoriasis into early and late types. TNF -308 polymorphisms can be associated with psoriasis susceptibility and severity. Potential genetic markers of psoriasis in populations with a complex mixture of ethnicities should be investigated.

Optimized photodynamic therapy with systemic photosensitizer following debulking technique for nonmelanoma skin cancers.

BACKGROUND: The thickness and depth of invasion of skin tumors may be limiting factors for topical photosensitizer-based photodynamic therapy (PDT). The use of PDT with systemic photosensitizer needs to be further explored as a modality of treatment for nonmelanoma skin cancer (NMSC). OBJECTIVE: The objective was to present six patients with multiple, nodular, and/or pigmented NMSC treated successfully with purified hematoporphyrin derivative (PHD) and PDT using prior debulking. METHODS: After 24 hours of systemic PHD (1.5 mg/kg), 12 lesions of NMSC were selected for PHD-PDT alone and 6 nodular/elevated lesions for PHD-PDT following a debulking procedure. The tumor area was illuminated in one single-dose session of 300 J/cm(2), at an intensity range of 130 to 150 mW/cm(2), with a 630-nm-wavelength diode laser. RESULTS: The prior curettage provided significant reduction in volume and/or pigmentation of lesions. After the session of PHD-PDT with prior curettage and additional topical 20% ALA-PDT in two lesions or PHD-PDT alone, 83% (5/6) of lesions and 58% (7/12) of lesions, respectively, maintained a complete clinical response, 22.2+/-8.9 months of follow-up. CONCLUSIONS: The combination of prior debulking with systemic agents-PDT appears to be a good option for multiple, pigmented, and/or nodular lesions of NMSC and can allow the improvement of clinical results.

Pituitary-gonadal hormones and interleukin patterns in leprosy.

The functional status of pituitary-gonadal hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous (LL/BL) and tuberculoid (TT/BT) poles of leprosy were investigated. Gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and C-reactive protein (CRP) concentrations and erythrocyte sedimentation rate (ESR) were significantly higher in LL/BL leprosy patients than in controls and were not different from controls in TT/BT patients. LH and FSH were positively correlated with IL-1beta, IL-6 and TNF-alpha, and CRP concentrations and ESR. Testosterone plasma levels were significantly decreased in LL/BL patients and not different in TT/BT patients compared with controls. In addition, testosterone levels were inversely correlated with IL-6 and TNF-alpha. Prolactin plasma levels of both LL/BL and TT/BT patients were not different when compared with those of controls. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. The significant correlations between gonadotropins and testosterone and cytokines in leprosy patients suggest that cytokines may have a direct influence at testicular level and may be of pathogenetic significance in leprosy and in other inflammatory states involving reproductive dysfunction.

Adrenocortical hormones and interleukin patterns in leprosy.

The functional status of adrenocortical hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of leprosy were investigated. Interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha plasma levels, C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL (lepromatous) leprosy patients than in control subjects. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma levels were not different between patients and control subjects. In contrast, adrenal androgen dehydroepiandrosterone sulphate (DHEA-S) plasma levels were significantly lower in leprosy patients than in sex-matched control subjects. There was a significant inverse correlation between DHEA-S and IL-6, TNF-alpha, and CRP concentrations. This finding may be of pathogenetic significance in this disease and in other inflammatory states.

Disseminated mucocutaneous leishmaniasis resulting from chronic use of corticosteroid.

Mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin and mucosal lesions whose clinical manifestations can regress spontaneously, but with possible long subclinical evolution. The course of the disease is often related to the host immune response. The purpose of this article is to describe the clinical and microscopic findings of cutaneous and mucosal lesions of mucocutaneous leishmaniasis in a patient who presented an unusual form of the disease associated with an immunosuppressive state.

Psoríase e pseudo-hipoparatireoidismo / Psoriasis and pseudohypoparathyroidism

Relato de caso clínico de paciente do sexo masculino, de 24 anos de idade, com psoríase pustulosa havia dois meses. Apresentava antecedentes de crises convulsivas e retardo do desenvolvimento neuropsicomotor. Ao exame físico o sinal de Trousseau foi positivo, e a dosagem de cálcio no soro estava acentuadamente diminuída. O diagnóstico foi de psoríase pustulosa generalisada associada a pseudo-hipoparatireoidismo. Inicialmente o paciente foi tratado com etretinato, sem controle do quadro; porém, com detecçäo da hipocalcemia e a reposiçäo do cálcio, houve melhora acentuada das lesöes cutâneas. A remissäo completa foi obtida com a correçäo da hipocalcemia. Esses resultados indicam que a hipocalcemia estava diretamente relacionada com a manutençäo das lesöes de psoríase pustulosa generalizada e pseudo-hipoparatireoidismo