Managing the Patient with Psoriasis and Metabolic Comorbidities.

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

Prevalence of Non-Alcoholic Fatty Liver Disease in Adult Individuals with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: There are no published studies on the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with atopic dermatitis (AD). OBJECTIVES: To estimate the prevalence of NAFLD (assessed via liver ultrasonography) in adults with moderate-to-severe AD. METHODS: We performed a retrospective, cross-sectional, observational study including adult patients affected by moderate-to-severe AD, moderate-to-severe chronic plaque psoriasis, or a previous diagnosis of thin melanoma in situ (considered as the control group) who attended the Verona University Hospital between January 2022 and April 2023. Fatty liver was assessed via liver ultrasonography. RESULTS: A total of 144 adults with AD, 466 with chronic plaque psoriasis, and 99 with thin melanoma were included. The prevalence rates of ultrasound-detected NAFLD among patients with in situ melanoma, those with moderate-to-severe AD, and those with moderate-to-severe chronic plaque psoriasis were 23.2% (23 out of 99), 24.1% (36 out of 144), and 49.8% (228 out of 466), respectively (p < 0.01). Logistic regression analysis revealed that being of male sex, a higher age, a higher body mass index, and psoriasis were independently associated with NAFLD, whereas AD was not. CONCLUSIONS: Our findings show that the prevalence of ultrasound-detected NAFLD in patients with moderate-to-severe AD was comparable to that of patients with a previous diagnosis of in situ melanoma. It is plausible to hypothesize that the Th2-type inflammation typically characterizing AD is not a risk factor for NAFLD. Patients with moderate-to-severe psoriasis, but not those with AD, should be screened for NAFLD and other metabolic comorbidities.

Uncommon Non-Infectious Annular Dermatoses.

Several cutaneous diseases can present with annular lesions, making a distinction by physical appearance alone challenging. They can be distinguished into infectious and non-infectious, and common and uncommon annular dermatoses. Common non-infectious diseases include granuloma annulare, urticaria, and subacute lupus erythematosus. In addition, there are rare non-infectious non-neoplastic annular dermatoses whose nosographic attribution is established, including annually recurring erythema annulare centrifugum (EAC) and annular erythema in Sjögren syndrome and others whose nosographic positioning is still debated. They are neutrophilic figurate erythema, palpable migratory arciform erythema, eosinophilic annular erythema, and annular lichenoid dermatitis of youth. Their etiopathogenesis is largely unknown, although immune-mediated mechanisms are likely involved. It is difficult to establish if they are variants of reaction patterns or separate clinic-pathological entities. In fact, EAC and annually recurring EAC may represent different aspects of the same disease. Palpable migratory arciform erythema is hardly distinguishable from EAC deep type, Jessner-Kanof disease, and lupus tumidus. Neutrophilic figurate erythema and eosinophilic figurate erythema are clinically very similar and differing only in the relative proportion of eosinophils and neutrophils.

Reducing the Risk of Developing Psoriatic Arthritis in Patients with Psoriasis.

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory arthritis associated with psoriasis, which may manifest with different domains such as dactylitis, enthesitis, synovitis and spondylitis. The estimated prevalence of PsA in patients with psoriasis ranges widely between 6% and 42%. In most cases, PsA is preceded by skin involvement by an average time of 7-8 years. In the complex patho-mechanisms involved in the transition from psoriasis to PsA, the gut and skin have been proposed as the sites of immune activation triggering or contributing to the development of PsA. In such a transition, a subclinical phase has been identified, characterized by enthesopathy where soluble biomarkers and imaging findings but no clinical symptoms are detectable. Recent studies have provided some evidence that timely treated psoriasis may reduce the risk of developing PsA.

Milia-like calcinosis cutis in Down syndrome: a new case with a review of the literature.

We report an 11-year-old girl who presented with white papules on the dorsal and palmar region of the hands bilaterally. The parents reported that the lesions had appeared four months before and some had resolved spontaneously. The girl was suffering from celiac disease, Down syndrome, and alopecia areata treated with topical corticosteroids. At the first visit, the girl presented with alopecia areata, corticosteroid acne, and a dozen white papules located on the hands. On dermoscopy, a whitish structureless area was seen. Histological examination showed the presence of calcium deposits without tissue damage, thus confirming the diagnosis of milia-like idiopathic calcinosis cutis. At 6-month follow up, the lesions had completely disappeared. Milia-like idiopathic calcinosis cutis is a benign cutaneous disorder consisting of calcium deposits in an apparently undamaged dermis and is typically associated with Down syndrome. Up to a quarter of patients have coexisting syringomas. The milia-like papules tend to self-resolve as patients reach adulthood, so a wait-and-see approach is recommended.

Pruritus as a Distinctive Feature of Type 2 Inflammation.

Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients' quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy: A case series with systematic literature review.

The treatment of moderate to severe plaque psoriasis in patients with history of malignancy is challenging. To review the studies reporting the experience with IL-17A inhibitors in patients with psoriasis and history of malignancy; secondly, to investigate cancer recurrence in a series of patients with a prior malignancy and plaque psoriasis treated with IL-17A inhibitors. A systematic literature review and an observational retrospective analysis of patients with history of malignancy and plaque psoriasis treated with IL-17A inhibitors was performed. About 5 original articles out of 601 were retrieved, reporting a total of 10 patients with a median age of 59 years, interquartile range (IQR) 50-63. Seven patients were treated with secukinumab, one with ixekizumab and two with both sequentially. Although the stage ranged from in situ to IV stage, most of the cases were early-stage neoplasm. The IL-17A inhibitor was initiated after a median of 10 months, interquartile range (IQR) 5-30 (range 0-144) from the diagnosis of malignancy. In addition, a series of 12 patients with history of malignancy were identified from the University Hospital of Verona, including 9 cases with cancer in clinical remission and 3 with advanced disease at time of initiating IL-17 inhibitor. No malignancy recurrence was reported within a median of 12 (IQR 6-23) and 46 (IQR 36-48) months follow up in case series from literature and our experience, respectively. Data on use of IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy are limited. Registries and proactive pharmacovigilance activities are needed to guide clinical practice.

Incidence and ten-year follow-up of primary cutaneous lymphomas: a single-centre cohort study.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a rare group of extranodal non-Hodgkin lymphomas, and epidemiological data in Mediterranean countries are scarce. OBJECTIVE: To investigate the incidence and characteristics of PCL in a single tertiary referral centre in Italy. MATERIALS & METHODS: A total of 141 PCL patients, seen over a 10-year follow-up period, were investigated. RESULTS: Incidence rate of PCL was 0.8 cases/100,000 person years. T-cell lymphoma represented 78.7% of all cases, the majority being early mycosis fungoides (MF) (64%; median age: 66 years), followed by lymphomatoid papulosis (LyP) (19%; median: age 48 years), and others (median age: 72 years), including eight cases of anaplastic large CD30+ T-cell lymphoma, four CD4+ small-medium pleomorphic T-cell lymphoproliferative disorder, four Sézary syndrome, one subcutaneous panniculitis-like T-cell lymphoma, one extranodal NK/T-cell lymphoma nasal-type, and one angioimmunoblastic T-cell lymphoma. B-cell lymphoma accounted for 21.3% of PCL, with 20 cases of cutaneous follicular centre B-cell (median age: 63 years), four primary cutaneous marginal zone, three primary cutaneous diffuse large B-cell, and three leg-type lymphoma. Complete remission within the first year after diagnosis occurred in 70.4% of MF, 61.9% of LyP, 78.9% of other T-cell lymphoma, and 93.1% of B-cell lymphoma cases. Based on a Cox proportional hazard regression model, age, gender, stage, and lactate dehydrogenase and ß2-microglobulin blood levels did not predict clinical remission of MF or LyP. CONCLUSIONS: The incidence and characteristics of PCL in Italy are similar to those in other European countries. PCLs may be diagnosed at very early stages with good prognosis.

Kyrle's disease effectively treated with oral isotretinoin.

BACKGROUND: Kyrle's disease (KD) is a primary perforating dermatosis that affects more commonly 30-50 year old females, and clinically characterized by pruritic hyperkeratotic and ulcerated nodules, papules and plaques, localized on extensor surface of upper and lower limbs, and on the trunk. OBJECTIVE: To determine the effectiveness of the treatment with oral isotretinoin in KD. METHODS: We present the case of a 63-year-old woman with hyperkeratotic, erythematous-brown nodules and plaques localized on arms and legs, intensely itching; some lesions were ulcerated and discharging. Histology showed hyperplastic epidermis, cup-shaped invagination, degenerative basophilic material with plug formation. In the upper dermis, there was a dense lympho-histiocytic infiltrate. Narrow-band UVB and low dose oral corticosteroids were ineffective. Treatment with isotretinoin 20 mg/day was started with an excellent response in two months, and complete remission in the next four months. Isotretinoin was reduced to 10 mg/day for additional four months. In the next 9-month follow up, no recurrence of the disease was observed. CONCLUSIONS: Low-dose isotretinoin was very effective and well tolerated in our patient. One previous case treated with isotretinoin has been published.

Advanced Glycation End Products in the Pathogenesis of Psoriasis.

Advanced glycation end products (AGEs) are extremely oxidant and biologically reactive compounds, which form through oxidation of sugars, lipids and amino acids to create aldehydes that bind covalently to proteins. AGEs formation and accumulation in human tissues is a physiological process during ageing but it is enhanced in case of persistent hyperglycemia, hyperlipidemia and oxidative or carbonyl stress, which are common in patients with moderate to severe psoriasis. Exogenous AGEs may derive from foods, UV irradiation and cigarette smoking. AGEs elicit biological functions by activating membrane receptors expressed on epithelial and inflammatory cell surface. AGEs amplify inflammatory response by favoring the release of cytokines and chemokines, the production of reactive oxygen species and the activation of metalloproteases. AGEs levels are increased in the skin and blood of patients with severe psoriasis independently of associated metabolic disorders. Intensified glycation of proteins in psoriasis skin might have a role in fueling cutaneous inflammation. In addition, AGEs released from psoriatic skin may increase metabolic and cardiovascular risk in patients with severe disease.

Primary Cutaneous CD4+ Small/Medium Pleomorphic T-Cell Lymphoproliferative Disorder: A Case Series.

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is defined by a predominance of small- to medium-sized CD4+ pleomorphic T cells and a favorable clinical course. OBJECTIVE: We performed a retrospective analysis of 6 patients with CD4+ PCSM-LPD and reviewed the literature to address questions about its diagnosis, treatment, and prognosis. METHODS: Patients were 3 men and 3 women with a median age of 50 years. All patients presented with a single erythematous nodule, localised on the head in 4 patients and the upper trunk in 2 cases. No patients showed extracutaneous disease at any evaluation. Histopathologic features were characterised by nodular, diffuse, or, in 1 case, a superficial dense infiltrate of small/medium-sized pleomorphic CD4+/PD1+ T lymphocytes. T-cell receptor clonality was demonstrated in 5 cases. Treatment was surgical excision in 5 cases and radiotherapy in 1 case. RESULTS: All patients achieved complete resolution without relapses, during a median follow-up of 3 years. A review of the literature confirmed that CD4+ PCSM-LPD presents predominantly with a solitary nodular lesion on the face, neck, or upper trunk in adult patients. Surgical excision is the preferred treatment. Spontaneous resolution after biopsy may occur. CONCLUSIONS: CD4+ PCSM-LPD is a rare disorder with a favorable course.

Advanced Glycation End Products are Increased in the Skin and Blood of Patients with Severe Psoriasis.

Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products (AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild/severe psoriasis and 80 controls matched for age, sex and body mass index (40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normal-appearing skin by a standard fluorescence technique, and blood AGEs (total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs (p < 0.04), serum AGEs (p < 0.03) and pentosidine (p <0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs (r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score (r = 0.91, p < 0.0001). Receptor levels were lower (p < 0.001) in severe psoriasis, and inversely correlated with disease severity (r = -0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders.