Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Multisystem Inflammatory Syndrome in Children Associated with COVID-19: A Review with an Emphasis on Mucocutaneous and Kawasaki Disease-Like Findings.

BACKGROUND: COronaVIrus Disease 2019 (COVID-19) affects children with less severe symptoms than adults. However, severe COVID-19 paediatric cases are increasingly reported, including patients with Kawasaki disease (KD) or a multisystem inflammatory syndrome (MIS-C) that can present with features resembling KD. SUMMARY: MIS-C is an emerging severe paediatric syndrome associated with COVID-19 that can show overlapping features of KD, KD shock syndrome, and toxic shock syndrome. MIS-C might be an inflammatory disease distinct from KD resulting from an exaggerated immune response. A high prevalence of mucocutaneous manifestations - in addition to gastrointestinal and cardiovascular involvements - was found in MIS-C. The most frequent mucocutaneous findings were conjunctivitis and rash, often described as macular and/or papular or polymorphous. In this article, we present a brief overview of MIS-C with an emphasis on mucocutaneous findings and the relationship with KD.

Spreading Allergic Contact Dermatitis to Tea Tree Oil in an Over-the-Counter Product Applied on a Wart.

Tea tree oil is an essential oil obtained by distillation from the leaves and terminal branchlets of Melaleuca alternifolia and is now present in numerous products for body care and self-medication. We report a case of allergic contact dermatitis to tea tree oil in a young man who was applying a lotion containing tea tree oil on a wart localized on the plantar aspect of the right big toe, which had previously been treated with cryotherapy. He developed a severe eczematous eruption on the right foot and the right leg, with subsequent id reactions affecting the right thigh, the contralateral lower limb, the trunk and the upper limbs. The lotion was discontinued, and the dermatitis resolved after topical corticosteroid therapy. Patch testing with the aforementioned lotion 10% pet. and oxidized tea tree oil 5% pet. identified tea tree oil as the culprit agent of the dermatitis. This case report confirms that products made of natural ingredients, often perceived to be harmless, can cause allergic reactions.

The Role of Platelets in Chronic Urticaria.

BACKGROUND: Platelets are implicated in many pathophysiological processes, including inflammation and immunity. Ever-growing evidence suggests the active involvement of platelets in the pathogenesis of various inflammatory disorders, including cutaneous inflammatory diseases. A limited number of studies have investigated the role of platelets in chronic urticaria (CU). In this review, we summarize the current knowledge regarding the role of platelets in chronic spontaneous and inducible urticarias. METHODS: A literature search was performed using PubMed and Google Scholar, and the references of relevant literature were reviewed. RESULTS: Overall, in CU patients, conflicting results have been obtained from the assessment of platelet indices, such as mean platelet volume, platelet count and distribution width, as well as markers of platelet aggregation and activation. Nevertheless, a few studies showed significant changes of such parameters in CU patients compared to controls, in apparent correlation with clinical severity, autoreactivity and/or inflammatory status. CONCLUSIONS: In the absence of definitive conclusions, the pathogenic role of platelets in CU needs to be further explored. Platelets might represent a link between inflammation, coagulation and histamine release in the pathophysiological network of CU.

Daylight photodynamic therapy with methyl-aminolevulinate for the treatment of actinic cheilitis.

Actinic cheilitis (AC) is a common premalignant condition that requires an effective treatment to reduce the risk of malignant transformation. Photodynamic therapy (PDT) has been recently added to the armamentarium available for AC treatment. Daylight PDT (D-PDT) is a novel PDT modality in which the activation of the topical photosensitizer is induced by the exposure to natural daylight instead of artificial light sources without preliminary occlusion. This simplified procedure was found to be more tolerated as compared to conventional PDT. We report our preliminary experience on the use of D-PDT using methyl-aminolevulinate cream in 10 patients with refractory AC of the lower lip. Patients received two consecutive D-PDT sessions with an interval of 7-14 days. At 3 months after therapy, a complete response was observed in seven patients, with sustained results in five patients over an observational period of 6-12 months. Treatment was well tolerated.

Epidemiology of pediatric psoriasis: a population-based study using two Italian data sources.

BACKGROUND: Psoriasis can be associated with certain comorbidities. This information is important for family pediatricians (FPs) and general practitioners (GPs) who have a key role in the identification and management of skin diseases. This study aimed to assess the incidence and prevalence rates of pediatrics psoriasis and its association with specific comorbidities. METHODS: A retrospective cohort study was performed in patients aged less than 18 years registered in two Italian primary care databases (Pedianet and HSD) between 2015 and 2019. Prevalence and incidence of psoriasis were estimated, and a case-control design was adopted to assess specific comorbidities in psoriasis patients. RESULTS: The annual prevalence rate of psoriasis was 0.2% in Pedianet and between 0.5% and 0.7% in HSD. The incidence rate ranged from 0.47 to 0.58 and from 1.3 to 1.77 per 1000 person-years in Pedianet and HSD, respectively. Allergic rhinitis, asthma, celiac disease, other malabsorption disease and non-infective cutaneous diseases showed a statistically significant association with psoriasis in Pedianet, while no statistically significant difference was found in HSD. CONCLUSION: Given the FP-GP transition of patients, there is a need for accurate registration of clinical correlates, enabling GPs to implement strategies to minimize the lifetime risk of psoriatic progression.

Keratosis Pilaris-like Eruption during Treatment of Chronic Myeloid Leukemia with Tyrosine Kinase Inhibitors: Literature Review and Report of a Case Related to Imatinib.

The advent of tyrosine kinase inhibitors (TKIs) blocking BCR-ABL activity has revolutionized the therapeutic management of patients with chronic myeloid leukemia (CML). Adverse cutaneous reactions (ACRs) are common nonhematologic adverse events associated with the use of BCR-ABL TKIs. A characteristic pattern of eruption resembling keratosis pilaris (KP) has been described in patients treated with these drugs, especially nilotinib and dasatinib. The pathogenesis of this ACR is still unknown. This type of reaction appears to be uncommon with imatinib. Here, we report the case of an elderly patient with an asymptomatic KP-like eruption, which appeared one month after starting treatment with imatinib for CML. The case presentation is accompanied by a review of similar reactions in patients with CML treated with BCR-ABL inhibitors, attempting to make an excursus on the molecular targets of such drugs and possible mechanisms underlying this ACR.

Granulomatous Secondary Syphilis: A Case Report with a Brief Overview of the Diagnostic Role of Immunohistochemistry.

The diagnosis of syphilis can be challenging for dermatologists and dermatopathologists. In particular, secondary syphilis can have different clinical and histopathological presentations. A granulomatous tissue response is an unusual finding in secondary syphilis. We report the case of a 77-year-old man who presented with a 4-week history of non-pruritic generalised macules, papules, nodules and plaques. Histopathologically, there was a dense perivascular and periadnexal lympho-histiocytic dermal infiltrate with non-palisading and non-caseifying epithelioid granulomas and abundant plasma cells. The diagnosis of syphilis was confirmed by serology and immunohistochemical detection of Treponema pallidum in the biopsy specimen. A brief overview of the diagnostic role of immunohistochemistry is also provided, with particular emphasis on reported cases of granulomatous secondary syphilis.

Safety of anti-TNFα agents in the treatment of psoriasis and psoriatic arthritis.

CONTEXT: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations. OBJECTIVE: This review presents and discusses current evidence on the safety of anti-TNFα agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance. METHODS: Key studies on the safety of anti-TNFα agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA), were included as appropriate when data in psoriatic disease were unavailable or insufficient. RESULTS: Available data on the safety of anti-TNFα agents such as etanercept in psoriasis and PsA appear reassuring, even if some concerns still exist. Most notably, data suggest a higher incidence of infection and lymphoma amongst patients treated with the anti-TNFα monoclonal antibodies infliximab and adalimumab compared with etanercept. CONCLUSION: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity.

The Intriguing Links between Psoriasis and Bullous Pemphigoid.

The coexistence of psoriasis with autoimmune bullous diseases (AIBDs), particularly bullous pemphigoid (BP), has been documented in case reports and series, as well as in epidemiological studies. The onset of psoriasis precedes that of BP in the majority of cases. Patients with concomitant BP and psoriasis are generally younger at the onset of BP and present with fewer erosions and blisters as compared with patients suffering from isolated BP. Intriguingly, it has been speculated that some BP cases with comorbid psoriasis can actually correspond to anti-laminin gamma-1 pemphigoid, a rare form that was recently recognized as a distinct entity and which can mimic BP and/or other subepidermal AIBDs. The pathomechanisms underlying the BP-psoriasis association have not yet been identified, although several hypotheses have been proposed. The most credited among such hypotheses involves the so-called "epitope spreading" phenomenon, with tissue injury secondary to a primary inflammatory process (i.e., psoriasis) leading to the exposure of sequestered antigens evoking a secondary autoimmune disease (i.e., bullous pemphigoid). This narrative review aims to give a brief overview of the association between psoriasis and BP, examining epidemiological, clinical, and immunopathological features, the pathomechanisms underlying this association, the treatments for psoriasis incriminated as potential triggers of BP, and the therapeutic management of patients with psoriasis and BP.

Treatment of Severe Atopic Dermatitis with Dupilumab in Three Patients with Renal Diseases.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that can affect patients' quality of life. Dupilumab is the first biologic agent approved for the treatment of patients with inadequately controlled moderate-to-severe AD and its mechanism of action is based on the inhibition of the interleukin (IL)-4 and IL-13 signaling. There are only a few data on the safety of dupilumab in AD patients with comorbidities, including kidney disorders. MATERIALS AND METHODS: Descriptive retrospective series of three patients with chronic kidney diseases (Alport syndrome, IgA nephropathy, and hypertensive nephrosclerosis, respectively) receiving dupilumab for their concomitant severe AD. RESULTS: Treatment with a standard dosage of dupilumab caused a relevant improvement of AD in all patients without any adverse events or worsening of renal function. In a patient with severe renal failure, the drug was effective and well tolerated without the need for any dose adjustments, also after the initiation of peritoneal dialytic treatment. CONCLUSION: Our case series suggests the use of dupilumab as an effective and safe treatment for AD patients suffering from renal diseases, although additional studies are required to confirm such preliminary findings.

Circulating Irisin Levels in Patients with Chronic Plaque Psoriasis.

Irisin is an adipo-myokine, mainly synthetized in skeletal muscles and adipose tissues, that is involved in multiple processes. Only a few studies have evaluated serum irisin in psoriatic patients. This study aims to analyze serum irisin levels in patients with chronic plaque psoriasis, to compare them with values in controls, and to assess whether concentration of circulating irisin correlates with the severity of psoriasis, calculated by means of Psoriasis Area and Severity Index (PASI). We enrolled 46 patients with chronic plaque psoriasis; the control group included 46 sex- and age-matched subjects without any skin or systemic diseases. Serum irisin levels were measured by competitive enzyme linked immunosorbent assay. Our results showed a non-significant increase in serum irisin concentration in psoriatic patients compared to controls. A negative non-linear correlation between PASI and irisin levels was detected in psoriatic patients. Indeed, dividing patients according to psoriasis severity, the negative association between irisin and PASI was stronger in patients with mild psoriasis than in patients with higher PASI scores. Several control variables we tested showed no significant impact on serum irisin. However, erythrocyte sedimentation rate in the normal range was associated with significantly higher irisin levels in psoriatic patients. In conclusion, although irisin levels were not significantly different between controls and psoriatic patients, irisin was found to be negatively associated with psoriasis severity, especially in subjects with low PASI scores; however, further studies are needed to clarify the role of irisin in subjects with psoriasis.

Pustular Psoriasis: From Pathophysiology to Treatment.

Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed.

An overview of delayed pressure urticaria with special emphasis on pathogenesis and treatment.

Delayed pressure urticaria (DPU) is a physical urticaria characterized by the development of deep swellings at sites of pressure application on the skin. Etiopathogenesis of DPU is still unknown, although the available evidence suggests the involvement of mast cells through non-immunologic mechanisms and the role of several mediators beyond histamine, such as proinflammatory cytokines. The management of DPU is complex, also considering that prevention is very difficult and DPU frequently coexists with chronic "idiopathic" urticaria. Moreover, H1-antihistamines, which are the mainstay of treatment for common urticaria, usually provide less satisfactory results as compared with other urticarias. Therefore, numerous treatment alternatives have been proposed for severe refractory cases, such as oral or topical corticosteroids and various drugs with anti-inflammatory effects.

Anti-NuMA antibodies in a psoriatic patient: considerations about clinical relevance and effect of infliximab treatment.

Antibodies against the nuclear mitotic spindle apparatus protein (NuMA) are infrequently detected during antinuclear antibodies testing on HEp-2 cells. In a series of 428 psoriatic patients anti-NuMA antibodies were found only in a patient, at a titer of 1:640, without any apparent clinical relevance. The significance of anti-NuMA is not yet known and is briefly reviewed, also in consideration of potential therapeutic implications. Although biologic drugs targeting tumor necrosis factor-alpha have been associated with the development of non-organ specific autoantibodies and rare reports of autoimmune phenomena, infliximab was well tolerated in this patient and caused no changes in autoantibody titers.

Resistant cases of psoriatic arthritis: how to manage them.

Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2%-3% of the Caucasian population. Psoriatic arthritis (PsA), which occurs in up to one-third of patients with psoriasis, has a heterogeneous pattern expressed by various manifestations, including mono-oligoarthritis, an erosive and destructive polyarthritis indistinguishable from rheumatoid arthritis (RA), and spondyloarthropathy with axial involvement or enthesitis. Early detection of inflamed joints or axial involvement in patients with PsA is important in order to reduce inflammation and prevent joint destruction, deformity, and functional disability. The treatment of moderate-severe PsA has tended to include the same disease modifying antirheumatic drugs used to treat RA, but there is much less evidence supporting their efficacy and essentially none demonstrating that they slow radiographic joint destruction in PsA. A number of clinical trials have shown that tumor necrosis factor antagonists are generally safe and efficacious in the treatment of PsA, and can inhibit the progression of radiographic damage.

A matrix assisted laser desorption ionization time-of-flight mass spectrometry investigation to assess the composition of cod liver oil based products which displayed a different in vivo allergenic power.

Cod liver oil is a well-known "nutraceutical", which contains a wide range of substances, including triacylglycerols (TAGs), mono- and di-acylglycerols, free fatty acids, vitamins and n-3 polyunsaturated fatty acids. Topically applied, cod liver oil contributes to faster wound healing and improvement in skin quality. We recently reported a case of allergic contact dermatitis to cod liver oil contained in a topical ointment, in whom the patch test reaction with the ointment containing cod liver oil at a concentration of 40% was stronger than the reaction induced by a pure cod liver oil at the same concentration. We hypothesized that the different reactivity could be explained by differences in composition of the two products. In order to verify this hypothesis, we assessed the composition of those products using a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The results obtained showed that the spectra of the ointment and of the cod liver oil samples were very similar, even if a major number of peaks were observable in the higher mass range of the spectra relevant to the analysis of the ointment sample, that have been assigned to higher molecular weight TAGs. Our results suggest that the different reactivity to the two products could be due to differences in the amount of contained TAGs. TAGs may favor the penetration of the allergen(s) or may be the direct culprit substances, taking into account that TAGs have been reported to have sensitizing properties.