Fast and safe clinical response to sonidegib in a 98-year old woman affected by locally advanced basal cell carcinoma.

A 98-year-old woman presented with histologically confirmed locally advanced basal cell carcinoma of the face. A multidisciplinary approach excluded surgery because of the site near sensitive organs, extension, age, and comorbidities. Patient and caregivers declined radiotherapy considering the necessity of multiple hospital appointments. The patient was then placed on therapy with sonidegib, an oral inhibitor of the Hedgehog signaling pathway. There was a very rapid clinical response after only 28 days of treatment. The basal cell carcinoma improved progressively, with no adverse events reported. This case illustrates the efficacy and safety of this treatment in an advanced age patient. This treatment had a remarkably positive impact on quality of life, including that of the caregivers.

Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis.

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18-75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020-August 2023. Upadacitinib survival was investigated through Kaplan-Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.

A case of nivolumab-induced bullous pemphigoid successfully treated with dupilumab.

A 76-year-old man came to our attention for the presence of itchy skin lesions localized on the trunk. The patient had a nodular melanoma removed two years earlier. Because of metastatic pulmonary melanoma, he underwent a lung lobectomy and began adjuvant therapy with nivolumab. After six months of treatment, the patient reported the appearance of itchy lesions on the trunk that were diagnosed as eczema and successfully treated with systemic corticosteroids. Upon corticosteroid discontinuation, the eruption relapsed presenting with erythematous macules, tense blisters, and erosions on the trunk and limbs. The presence of linear deposits of IgG and C3 at the dermo-epidermal junction and high serum levels of anti-BP180 antibodies confirmed the suspicion of nivolumab-induced bullous pemphigoid. Treatment with 0.6mg/kg methylprednisolone and 200mg/day doxycycline as well as nivolumab discontinuation induced temporary remission. After tapering methylprednisolone to 16mg/day, the patient developed new blisters. Therefore, dupilumab 300mg every other week was added with progressive improvement while methylprednisolone was tapered down and withdrawn after four months. After six months the patient was still in full clinical remission. Many cases of conventional bullous pemphigoid have been treated successfully with dupilumab, which can also be used safely in cancer patients without inducing overt immunosuppression.

A Disseminated Mycobacterium Abscessus Infection in a Patient Affected by Pulmonary Graft versus Host Disease: Case Report with a Revision of Literature.

Mycobacterium abscessus complex, hereinafter Mab, is a taxonomic group of rapidly growing, nontuberculous mycobacteria (NTM). Despite major advances in understanding virulence, pathogenicity and mechanism of antibiotic resistance, Mab remains a significant cause of pulmonary and extra-pulmonary disease. Herein, we describe a disseminated, macrolide-resistant, Mab subspecies abscessus infection occurring in a severely immune-compromised 34-year-old allotransplanted female patient affected by pulmonary chronic graft versus host disease (cGVHD). The infection was characterized by hematogenous spread, and besides lungs, it involved skin, and soft tissues, resulting in a highly debilitating, painful, and finally fatal disease. Our case describes the severe impact of Mab infections in the setting of allogeneic hematopoietic stem cells transplant (alloHSCT) and related complications. It also highlights the unmet need of preventive and surveillance measures together with the urgency of developing effective vaccines and drugs against emerging NTM. The scarce literature regarding Mab infections in alloHSCT patients is also reviewed.

Pyoderma gangrenosum associated with pseudo-Pelger-Huet anomaly in a patient with idiopathic myelofibrosis.

Pseudo-Pelger-Huët anomaly is a condition in which almost all the granulocytes are hyposegmented and/or hypogranulated. It is typically recognized in peripheral blood smears and represents a marker of several disorders, such as myeloproliferative diseases and myelodysplasia. The occurrence of the pseudo-Pelger-Huët anomaly in the cutaneous infiltrate of pyoderma gangrenosum is very rare. We describe the case of a 70-year-old man with idiopathic myelofibrosis who developed pyoderma gangrenosum. Histological examination showed an infiltrate consisting of granulocytic elements with features of dysmaturity and segmentation anomalies (hypo- and hypersegmented forms), suggestive of pseudo-Pelger-Huët anomaly. Methylprednisolone treatment resulted in progressive improvement of pyoderma gangrenosum.

A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years' Experience of the GISM Network.

Systemic mastocytosis (SM) and other adult clonal mast cell disorders (CMD) are often underestimated, and their epidemiology data are scarce. We aimed at evaluating the impact of the activity of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona on the prevalence and incidence of CMD. We examined the data of 502 adult patients diagnosed with CMD and residing in the Veneto Region, consecutively referred to GISM between 2006 and 2020. SM was diagnosed in 431 cases, while 71 patients had cutaneous mastocytosis or other CMD. Indolent SM represented the most frequent SM variant (91.0%), mainly with the characteristics of bone marrow mastocytosis (54.8%). The prevalence of SM in the adult population of the Veneto region and of the Verona province was 10.2 and 17.2/100,000 inhabitants, respectively. The mean incidence of new SM cases in Verona was 1.09/100,000 inhabitants/year. Hymenoptera venom allergy was the main reason (50%) leading to the CMD diagnosis. Osteoporosis, often complicated by fragility fractures, was present in 35% of cases, even in young patients, especially males. Our data show a higher prevalence and incidence of SM than previously reported, confirming that reference centers with multidisciplinary approach are essential for the recognition and early diagnosis of CMD.

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.

Systemic Mastocytosis: Multidisciplinary Approach.

Systemic mastocytosis (SM) is a heterogeneous group of diseases that affect almost exclusively adults and are defined by the proliferation and accumulation of clonal mast cells (MC) in various tissues. Disease subtypes range from indolent to rare aggressive forms. Although SM is classified as a rare disease, it is believed to be likely underdiagnosed. Major signs and symptoms mainly depend on MC activation and less frequent organ infiltration, typical of more aggressive variants. Diagnosis may be challenging, and symptoms can be aspecific and involve several organs. Therefore, it is advisable to refer patients to specialized centers, having sufficient knowledge of the disease, sensitive diagnostic procedures, offering a personalized and multidisciplinary diagnostic approach, including at least hematological, allergological, dermatological, and rheumatological evaluations. A precise and timely diagnosis is required for: a) adequate counseling of patients and their physicians; b) beginning of symptomatic treatment (anti-mediator therapy); c) prevention of severe manifestations of the disease (i.e., recurrent anaphylaxis, osteoporosis, and bone fractures); d) cytoreductive treatment of advanced SM variants. This review summarizes the disease's main manifestations and describes the ideal diagnostic approach for adult patients with suspected SM, giving physicians the main notions for correct patient diagnosis and management. This review also highlights the importance of a multidisciplinary approach in this very complex disease.

Role of occupational and recreational sun exposure as a risk factor for keratinocytic non-melanoma skin cancers: an Italian multicenter case-control study.

BACKGROUND: Sun exposure is the main external risk factor for keratinocytic non-melanoma skin cancer (NMSC). Outdoor workers are at increased risk, but the relationship of NMSC with occupational solar exposure is often confounded by concurrent recreational sun exposure. We compared the percentage of outdoor workers in NMSC patients versus controls without history of NMSC and assessed occupational and recreational sun exposure in both groups, evaluating also other risk factors and use of protective measures. METHODS: Adult NMSC patients and controls without history of NMSC or actinic keratoses, matched for sex and age range, were recruited in the Departments of Dermatology of seven Italian University Hospitals, with a 1:2 patient/control ratio whenever possible. Data were collected using specifically designed questionnaires. RESULTS: Eight hundred thirty-four patients and 1563 controls were enrolled. History of outdoor work was significantly (P=0.033) more frequent in patients. Patients were more sun exposed from outdoor leisure activities (P=0.012) and sunbathed for longer periods (P=0.13) and between 12 pm and 3.30 pm (P=0.011). Cumulative sun exposure during hobbies was similar between patients and controls in outdoor workers, higher (P<0.05) in patients among indoor workers. Patients and controls with history of outdoor work were more sun exposed at work than during leisure activities (P<0.001). Use of sunscreens by outdoor workers was very low, particularly at work (19.9%). Patients used sunscreens more than controls (P=0.002). CONCLUSIONS: Occupational and recreational sun exposure are relevant risk factors for outdoor and indoor workers respectively. Sunscreens are alarmingly underused, particularly at work, and are used mainly by patients.

Eyelid Dermatitis and Contact Sensitization to Nickel: Results from an Italian Multi-Centric Observational Study.

BACKGROUND: Due to the sensitizing constituents of eye cosmetics, allergic contact dermatitis is considered a frequent cause of eyelid dermatitis. An association between eyelid dermatitis and nickel contained in make-ups remains controversial. OBJECTIVE: The study aimed to assess the association between nickel allergy, the use of pigmented makeup products and self-reported eyelid dermatitis. METHOD: This multi-centric, cross-sectional study enrolled 165 women sensitized to nickel (patients) and 103 women without intolerance to metals (controls). We recorded: demographics, atopy, use of pigmented eye cosmetics (mascara, eyeshadow, eyeliner, eyebrow pencil), and previous eyelid dermatitis. Among the patients, any co-sensitization to cosmetics or metals was recorded. RESULTS: 87.3% of the patients and 91.3% of the controls reported their use of eye make-up; 44.9% and 52.4%, respectively, reported previous episodes of eyelid dermatitis, without significant differences. The occurrence of eyelid dermatitis was significantly associated with the use of eye make-up products, both in general and considering each product separately. Age, atopy, or co-sensitization to other metals or cosmetics did not affect the occurrence of eyelid dermatitis. CONCLUSION: Nickel allergy should not be considered the main risk factor for eyelid dermatitis. The use of pigmented eye make-up may be a triggering factor for eyelid dermatitis, probably due to an irritant action.

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.

Keratosis lichenoides chronica: Case-based review of treatment options.

Keratosis lichenoides chronica (KLC) is a rare dermatological condition characterized by keratotic papules arranged in a parallel linear or reticular pattern and facial lesions resembling seborrheic dermatitis or rosacea. The clinical, histological and therapeutic information on 71 patients with KLC retrieved through a PubMed search plus one our new case were analyzed. KLC affects patients of all ages, with a modest male predominance. Pediatric cases represent about one quarter of patients. Diagnosis is usually delayed and histologically confirmed. All patients have thick, rough and scaly papules and plaques arranged in a linear or reticular pattern, on limbs (>80%) and trunk (about 60%). Face involvement is described in two-thirds of patients. Lesions are usually asymptomatic or mildly pruritic. Other manifestations, such as palmoplantar keratoderma, mucosal involvement, ocular manifestations, nail dystrophy, are reported in 20-30% of patients. Children present more frequently alopecia. No controlled trials are available. Results from small case series or single case reports show that the best treatment options are phototherapy and systemic retinoids, alone or in combination, with nearly half of patients reaching complete remission. Systemic corticosteroids as well as antibiotics and antimalarials are not effective.

Annular Lichenoid Dermatitis of Youth: Report of Six New Cases with Review of the Literature.

BACKGROUND: Annular lichenoid dermatitis of youth (ALDY) is an uncommon disease clinically reminiscent of morphea, annular erythema or mycosis fungoides. OBJECTIVE: To describe the histological and clinical features of a small series of patients with ALDY and to review the literature. PATIENTS: We describe the clinical and histological features of six patients (age range 7-79 years) with asymptomatic erythematous macules and patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histologically, all cases showed lichenoid dermatitis limited to the tips of rete ridges, with many intraepidermal CD8+ and some CD4+ T cells. T cell receptor rearrangement was absent in all cases. A total of 44 patients with a consistent clinical and histological picture have been described. The disease is sensitive to topical and/or systemic corticosteroids. CONCLUSIONS: ALDY is a unique lichenoid dermatitis for whose diagnosis a clinical-pathological correlation is essential. The disease typically affects young patients, more rarely adults and elderly.

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.

BACKGROUND: Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. OBJECTIVE: We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. METHODS: Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. RESULTS: In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). CONCLUSIONS: The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Histiocytoid Sweet syndrome is infiltrated predominantly by M2-like macrophages.

BACKGROUND: Histiocytoid Sweet syndrome (HSS) is a rare variant of Sweet syndrome (SS). The nature of histiocytoid cells is still uncertain. OBJECTIVE: We sought to offer a comprehensive overview on clinical features of HSS and further information on immunohistochemical phenotype of the infiltrate. METHODS: The clinical, histologic, and immunohistochemical features of 12 of our patients with HSS and all cases retrieved through a PubMed search were analyzed. RESULTS: Lesions consisted of erythematous-violaceous papules and plaques, randomly distributed mostly on the trunk and the limbs. Three patients had myelodysplastic syndrome and 1 had a monoclonal gammopathy. The infiltrate was mainly composed of CD68(+)CD163(+)myeloperoxidase(+)myeloid cell nuclear differentiation antigen(+)CD117(-)CD15(-)CD34(-), a phenotype suggestive of M2-like macrophages. A few mature neutrophils and lymphocytes were also present. Review of all HSS cases showed no sex predominance and no extracutaneous infiltrates; inconstant presence of fever and blood neutrophilia; association with hematologic or solid neoplasms (26%), autoimmune conditions (12%), and infectious diseases (10%); and good response to steroid treatment, with rare relapses or recurrences. LIMITATIONS: The study includes a limited case series. The pathogenesis of the disease remains to be clarified. CONCLUSIONS: HSS lesions are infiltrated mostly by M2-like macrophages. The clinical features present more similarities than differences with SS.

Bone involvement and osteoporosis in mastocytosis.

Bone involvement is frequent in patients with systemic mastocytosis. Osteoporosis is the most prevalent bone manifestation, but diffuse osteosclerosis or focal osteolytic or osteosclerotic lesions are not infrequent. The risk of osteoporotic fractures is high, especially at the spine and in men. Routine measurements of bone mineral density and vertebral morphometry are warranted. The bone turnover markers indicate the involvement of complex bone metabolism in mastocytosis-related manifestations. Bisphosphonates represent the first-line treatment for osteoporosis-related mastocytosis.

Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM.

BACKGROUND: Indolent systemic mastocytosis (ISM) without skin lesions (ISMs(-)) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs(+)). Interestingly, in almost one-half of ISMs(-) patients, MC-mediator release episodes are triggered exclusively by insects. OBJECTIVE: We aimed to determine the clinical and laboratory features of ISMs(-) associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. METHODS: A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs(-), 72 ISMs(-) triggered by other factors (otherISMs(-)), 56 ISMs(+), and 64 nonclonal MC activation syndrome, were studied. RESULTS: Compared with otherISMs(-) and ISMs(+) patients, insectISMs(-) cases showed marked male predominance (78% vs 53% and 46%; P < .001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 µg/L; P ≤ .009). Moreover, insectISMs(-) less frequently presented BM MC aggregates (46% vs 70% and 81%; P ≤ .001), and they systematically showed MC-restricted KIT mutation. CONCLUSIONS: ISMs(-) patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs(-) and ISMs(+) patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors.