Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly ...expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4
CD62L
T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.
Pyoderma gangrenosum is a rare and severe inflammatory skin condition. There are different variants, including generalised and atypical forms, but the most common presentation is an enlarging ulcer ...on the lower extremities. Treatment can represent a challenge for physicians and there are no guidelines based on randomised controlled trials. We report an exceptional case of widespread and refractory pyoderma gangrenosum in a middle‐aged woman where cocaine use may have played a role. Treatment with i.v. pulse corticosteroids and cyclosporine was ineffective, and disease control was obtained with oral corticosteroids together with mycophenolic acid, infliximab and abstinence from cocaine consumption. There was a temporal relationship between disease outbreaks and cocaine consumption and improvement after its discontinuation. In the present case such clinical severity without associated pathology and the temporal association with cocaine abuse raises the possibility of cocaine playing an aetiological role as well as accounting for therapy resistance.
Multicentric reticulohistiocytosis (MRH) is an uncommon non‐Langerhans cell histiocytosis of unknown etiology. It is a multisystem disorder characterised by a papulonodular skin eruption, mainly in ...the extensor surfaces, and destructive polyarthritis. Histologically, either cutaneous lesions or the synovium show a dense dermal infiltrate of histiocytes and multinucleated giant cells with an eosinophilic granular material in the cytoplasm. In the immunohistochemical analysis these cells stain positively with monocyte/macrophage markers (CD68 and CD45), as well as with certain cytokines (tumor necrosis factor‐α, interleukin 1β and interleukin 6). Moreover, recent reports suggest an osteoclastic nature of the infiltrating cells, as they stain strongly with osteoclast tissue lytic markers including tartrate‐resistant acid phosphatase and cathepsin K. We report a case of MRH presenting with clinical features of dermatomyositis. Furthermore, the patient showed elevated cytokine serum levels that lowered after therapy.
Sclerodermoid chronic graft-versus-host disease (scGVHD) is a severe complication of allogeneic haema-- topoietic stem cell transplantation. The aim of this study was to investigate the usefulness of ...high-frequency ultrasound of the skin in assessing the inflammatory patterns and prognosis of patients with scGVHD. A prospective study was carried out with patients who developed scGVHD in the period June 2016 to April 2018. Clinical and ultrasound examinations were performed on the first visit and at 6-month follow-up. A total of 24 patients were included in the study. A 6-month follow-up high-frequency ultrasound of the skin was performed on 20 of the 24 patients. Abnormal B-mode findings in high-frequency ultrasound of the skin consisted of hypoechogenic dermis, hypoechogenicity of septa and hyperechogenicity of lobules in hypodermis. No differences were observed in these basal parameters between treatment progressive/non-responding and inactive/responding scGVHD groups of patients. Basal Doppler showing increased vascular flow with a systolic peak ≥10 cm/s and a vascular resistance index ≥ 0.70 was observed only in those patients who developed progressive/non-responding scGVHD (62.5% vs 0% p = 0.006). In conclusion, Doppler ultrasound is a useful tool to assess the inflammatory activity and outcome of scGVHD. These findings could enhance patient management and help to guide treatment decisions.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Determining disease activity from clinical signs in patients with connective tissue panniculitis (CTP) is often challenging but is essential for therapeutic decision making, which largely relies on ...immunosuppressant treatment. High-frequency ultrasound (HFUS) may be useful in supporting such decisions by accurately determining CTP activity. This study aimed to investigate the accuracy of HFUS in identifying signs of CTP activity or inactivity and assess its usefulness in therapeutic decision making. A prospective cohort study of consecutive patients with biopsy-proven CTP receiving HFUS was conducted in a tertiary university hospital (2016-2020). HFUS was performed at inclusion and at each 3- or 6-month follow-up visit, depending on disease activity. Twenty-three patients with CTP were included, and 134 HFUSs were performed. In 59.7% (80) of the evaluations, the clinical presentation did not show whether CTP was active or not. In these cases, HFUS showed activity in 38.7% (31) and inactivity in 61.3% (49). In 71.25% (57) of the visits, HFUS was the determinant for therapeutic decisions. Further follow-up showed consistent clinical and HFUS responses in all unclear cases after treatment modification. HFUS appears to be a useful adjunct to the clinical examination for CTP to assess activity and make therapeutic decisions.
IMPORTANCE Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti–tumor necrosis factor (TNF) ...treatment of psoriasis. OBJECTIVE To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. DESIGN Retrospective series of patients with psoriasis who received anti-TNF therapy (infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. SETTING Two psoriasis referral centers. PARTICIPANTS Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. INTERVENTION Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. MAIN OUTCOMES AND MEASURES The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. RESULTS Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. CONCLUSIONS AND RELEVANCE Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.
Acute generalised exanthematous pustulosis (AGEP) is a rare toxicoderma characterised by an acute onset rash, with many sterile pustules on the surface, high fever and increased acute phase ...reactants. We report the case of a patient who presented to the dermatology department with an AGEP and polyarthritis, in which a novel CARD14 mutation was identified. The pathophysiological mechanism of AGEP remains unclear, although mutations in the IL36RN gene have been identified in a small subset of AGEP patients. Similarly, mutations in the CARD14 gene have been linked to pustular types of psoriasis and familiar cases of pityriasis rubra pilaris; however, there are no reports associating mutations in the CARD14 gene with AGEP.
Penttinen type of premature aging syndrome is an autosomal‐dominant disorder that can be caused by the c.1994T>A pVal665Ala pathogenic variant in platelet‐derived growth factor receptor‐B (PDGFRB). ...Imatinib, a receptor tyrosine kinase (RTK) inhibitor, has been used in Penttinen syndrome (PS) patients with good results. A 21‐year‐old male presented shortly after birth with a prematurely aged appearance with distinctive facial features and cutaneous atrophy with hypertrophic scar‐like lesions. Generalized brachydactyly with acro‐osteolysis was observed. Flexion contractures limited his daily activities. Cognitive impairment was not present. Genetic testing found a heterozygous variant c.1994T>A pVal665Ala in exon 14 of PDGFRB. A diagnosis of PS was made and imatinib treatment was started with partial response. After lack of further improvement, in vitro molecular studies with imatinib and dasatinib showed that the Val665Ala variant had greater sensitivity to dasatinib than imatinib. This was seen examining levels of P‐PDGFRB directly and on downstream ligands P‐AKT and P‐STAT. Improved clinical response was observed after treatment with dasatinib. We report a new case of PS with clinical and molecular response to dasatinib after incomplete response to imatinib. Our work provides further molecular and clinical evidence of RTK inhibitors' efficacy in this rare disorder.
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