Vascularization and fibrosis are important ultrasonographic tools for assessing response to adalimumab in hidradenitis suppurativa: Prospective study of 32 patients.

Hidradenitis suppurativa (HS) is a debilitating skin disease presenting with nodules, abscesses, and fistulae preferentially in the main folds. Adalimumab is the only licensed biologic for moderate-to-severe HS. Ultrasound demonstrated good sensitivity to provide anatomic and functional information in HS; in particular assessing vascularization, related to inflammation, and fibrosis in HS lesions before and after adalimumab treatment with ultrasound and Color Doppler may integrate clinical evaluation with imaging. Patients with moderate-to-severe HS were enrolled in this observational prospective study. Clinical evaluation (according to Hurley classification and International Hidradenitis Suppurativa Severity Score System score) and ultrasound (according to US HS-PGA)/Color Doppler were performed at baseline and after 12 weeks of adalimumab. Ultrasound was used for assessing fibrosis and Color Doppler for vascularization. For each patient, the three most severe lesions among abscesses and fistulae were chosen for total 96 lesions. Thirty-two patients were included, 18 men (56%) and 14 women (44%) with mean age 41.2. Mean IHS4 was 22.4 at baseline and dropped to 14.7 at week 12. Based on US HS-PGA, 14 out of 32 patients fell down by one or more classes of severity. Interestingly, adalimumab led to overall decrease in vascularization, particularly in lesions with intense vascular flow, which were 78 (81.3%) at baseline and became only 25 (26.04%). Finally, marked increase in fibrosis was seen after adalimumab, notably in lesions without fibrosis, which were 81 (84.4%) at baseline and became 15 (15.6%). This study confirms the efficacy of adalimumab in HS and provides value for vascularization and fibrosis as important ultrasonographic tools integrating clinical scores.

A case report of systemic mastocytosis associated with multiple hematologic non-mast cell lineage diseases.

Systemic mastocytosis (SM) is a hematological malignancy characterized by extracutaneous infiltration by atypical mast cells. Together with indolent SM, aggressive SM, and mast cell leukemia, the World Health Organization (WHO) recognizes another major disease subgroup: SM with an associated hematological neoplasm, which is characterized by the presence of a concurrent neoplasm, more commonly, a chronic myelomonocytic leukemia. While KIT D816V is commonly regarded as the driver mutation, the clinical presentation of SM is extremely varied. Treatment of SM might not be simple, but now more specific therapies tailored toward prognostic subgroups of patients have been developed. Here, we report a detailed description of clinical management and biological features of a systemic mastocytocis case associated with multiple hematologic non-mast cell lineage diseases.

Color Doppler as a tool for correlating vascularization and pain in hidradenitis suppurativa lesions.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, chronic-relapsing, inflammatory skin disease of apocrine gland-bearing skin, presenting with nodules, abscesses, and fistulae. Ultrasound is used to classify HS lesions but evaluation of vascularization, related to tissue inflammation, needs Color Doppler. The aim was to correlate vascularization of HS lesions with patients' reported pain. METHODS: Vascularization was assessed with Hitachi Arietta V-70 sonographer according to a four-category system ranging from absent (0), minimal (1), moderate (2) vascularization, and detectable vascular flow (3). Pain was scored with Numeric Rating Scale (NRS) from 0 to 10. RESULTS: Twenty-four patients were included, 13 men (54.2%) and 11 women with mean age of 37.2 (range: 19-61 years). Sixty-nine HS lesions were studied: none of the lesions with absence of vascularization was painful. Lesions with minimal vascularization had a mean NRS value of 3.1 (range: 0 to 7; standard deviation [SD]: 1.6). Lesions with moderate vascularization had a mean NRS value of 6.4 (range: 4-8; SD: 1.4). Lesions with intense vascular flow had a mean NRS value of 7.8 (range: 5-9; SD: 1.7). Correlation Spearman's rank coefficient calculated between the class of vascularization and the mean NRS value was 0.98, supporting high correlation between intensity of vascularization and local pain. CONCLUSION: The present study is the first one demonstrating correlation between vascularization of HS lesions assessed with Color Doppler and local pain. Color Doppler may be a dynamic diagnostic tool that can address the therapeutic approach and assess response to treatment in HS.

Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients.

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations. Am. J. Hematol. 91:692-699, 2016. © 2016 Wiley Periodicals, Inc.

Intramuscular Polydeoxyribonucleotides in Fibrotic and Atrophic Localized Scleroderma: An Explorative Prospective Cohort Study.

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI-73.7%, mLoSDI-43.9%, PGA-A-60.4%, PGA-D-40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration.

Comparison of clinical and sonographic scores in hidradenitis suppurativa and proposal of a novel ultrasound scoring system.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease that presents with nodules, abscesses and fistulae affecting the apocrine gland-bearing skin. Since few years, ultrasonography is used to better characterize HS skin lesions but comparison between clinical and sonographic scores has been made only in small series of patients. To assess concordance between clinical and sonographic scores in a larger cohort of HS patients. METHODS: We conducted a retrospective observational study on 140 HS patients comparing two clinical score systems, Hurley and HS-Physical Global Assessment (PGA), with two ultrasonographic scores, sonographic score of hidradenitis suppurativa (SOS-HS) and ultrasonographic HS-PGA, a novel ultrasound scoring system set up by our group. We used the weighted Cohen's Kappa statistic (k) to evaluate the agreement. RESULTS: Agreement between Hurley staging and SOS-HS was found in 61.4% of patients (weighted kappa 0.477), while agreement between clinical and ultrasonography HS-PGA scores was found in 35% of patients (weighted kappa 0.278), both findings suggesting a substantial disagreement. CONCLUSIONS: Our study demonstrated a relevant disagreement between clinical and ultrasonography scores. Ultrasonography discovered non-clinically evident HS lesions, notably fistulae. Taken together, the above findings may support the view, previously suggested in expert panel reports, on the higher sensitivity of ultrasonography compared to clinics in HS.

A case of aggressive systemic mastocytosis with bulky lymphadenopathy showing response to midostaurin.

Management of systemic mastocytosis is an emerging challenge which requires a multidisciplinary diagnostic approach and personalized treatment strategy. Midostaurin can rapidly reduce the disease burden, also in cladribine refractory cases.

Detection of IgE autoantibodies in mucous membrane pemphigoid and their association with disease severity.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune disease characterized by scarring lesions at mucosal sites. Although the pathogenic role of specific IgG and/or IgA has been already demonstrated and the detection of these immunoglobulins is a criterion in the diagnosis of MMP, little is known about IgE role in this disease. Therefore, the main purpose of this study was to assess the presence of circulating and tissue bound IgE in patients with MMP and their possible correlations with clinical presentation and disease course. METHODS: We conducted a retrospective study on 29 patients affected by MMP, recruited from a single center. Direct and indirect immunofluorescence studies were assessed to analyze the presence of specific IgE directed against the basal membrane zone. For each patient, fluorescence data were compared to clinical features. RESULTS: Linear deposits of C3, IgG and IgA were present in 86.2%, 62% and 37.9% of cases respectively, while IgE linear deposits were detected in 17 out of 29 patients (58.6%) including one case with isolated IgE positivity. Circulating IgE and IgA anti-BMZ were present in 7 (24.1%) and 5 (17.2%) patients, respectively. Both the presence of circulating IgA and of tissue bound IgE deposits correlated with disease activity index (P<0.014). CONCLUSIONS: Our results demonstrated the presence of IgE autoantibodies in MMP, particularly in more severe cases. Thus, IgE detection may represent an additional useful diagnostic tool in this disease.

Hidradenitis suppurativa/acne inversa: a prospective bacteriological study and review of the literature.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle that usually involves specific anatomic areas which are partially occluded, have a higher density of eccrine and apocrine sweat glands and a higher pH. These characteristics could promote the superinfection of certain group of bacteria. We aimed to describe the bacteria that can be isolated from hidradenitis lesions and to establish a correlation between bacteriological results and clinical data. METHODS: We prospectively enrolled forty-six patients presenting purulent or seropurulent discharge. Sixty samples were performed using swabs, which were deeply introduced in the lesions. RESULTS: Fifty-two percent of cultures resulted positive and fifteen bacterial species were isolated. The more prevalent species were Proteus mirabilis and Staphylococcus aureus. Samples from advanced cases were more likely to yield a positive bacterial growth. CONCLUSIONS: In our study the rate of positive cultures increased in more severe stages of the disease, thus bacterial superinfection of established lesions may contribute to maintain chronic inflammation. We could not find statistically significant correlation with the sampled anatomic area or specific group of bacteria. Larger prospective studies should be performed.

A Systematic Review of Treatment Options and Clinical Outcomes in Pemphigoid Gestationis.

Background: Treatment regimens for pemphigoid gestationis (PG) are non-standardized, with most evidence derived from individual case reports or small series. Objectives: To systematically review current literature on treatments and clinical outcomes of PG and to establish recommendations on its therapeutic management. Methods: An a priori protocol was designed based on PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched for English-language articles detailing PG treatments and clinical outcomes, published between 1970 and March 2020. Results: In total, 109 articles including 140 PG patients were analyzed. No randomized controlled trials or robust observational studies detailing PG treatment were found. Systemic corticosteroids ± topical corticosteroids and/or antihistamines were the most frequently prescribed treatment modality (n = 74/137; 54%). Complete remission was achieved by 114/136 (83.8%) patients. Sixty-four patients (45.7%) were given more than one treatment modality due to side effects or ineffectiveness. Leaving aside topical corticosteroids as monotherapy ± antihistamines in patients with mild disease, systemic corticosteroids ± topical corticosteroids and/or antihistamines led to complete remission in the highest proportion of patients (83%), while steroid-sparing treatments ± topical corticosteroids and/or antihistamines were associated with the lowest proportion of flares (55.5%). Limitations: The review has been drafted based on a limited number of single case reports and small case series. Underreporting/underdiagnosis of patients with mild-to-moderate PG, partial/absent follow-up, absence of precise description of neonatal outcomes and lack of validated objective scores for measuring disease severity are other limitations of our study. Our systematic review was affected by publication bias. Conclusion: Systemic corticosteroids are the most frequently used treatment for PG. Whilst most patients achieve complete remission, many of them have refractory/persistent disease requiring multiple lines of therapy. Therefore, we provided an algorithm for PG treatment integrating the results of this systematic review with current knowledge available for bullous pemphigoid. High-quality studies will further help assess the effectiveness of different treatment options for PG.

Prevalence of Neuropathic Pain and Related Characteristics in Hidradenitis Suppurativa: A Cross-Sectional Study.

BACKGROUND: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. METHODS: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])-II (45.5%)-III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies.

Linear IgA bullous dermatosis in adults and children: a clinical and immunopathological study of 38 patients.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepithelial vesiculobullous disease due to IgA autoantibodies directed against different antigens of the basement membrane zone (BMZ) of the skin and/or mucosae. It affects mainly preschool-aged children and adults, with only few studies on large series. The aim of this study was to assess possible differences between adults and children regarding clinical presentation, immunopathologic features, management and course of the disease. METHODS: A retrospective review of 38 LABD patients, followed-up from November 2006 to September 2018, was performed. RESULTS: Of 38 patients, 27 were adults and 11 children. Mean age at diagnosis was 5.4 years and 60.6 years in the pediatric and adult group, respectively. Considering both groups, limbs were the most commonly involved site (73.7%), followed by trunk (55.3%), head (36.8%) and buttocks (13.2%). Interestingly, head (p = 0.008), particularly perioral (p = 0.001), involvement, as well as "string of pearls" arrangement (p = 0.03), were more prevalent in children. Mucosal involvement was seen in 9 (23.7%) patients and was more frequent in children than adults (45.5% vs 14.8%, respectively, p = 0.09). Linear IgA deposits along the BMZ were observed in 30 patients (78.9%), while linear/granular IgA deposits in 8 patients (21.1%). Dapsone was the most commonly used drug (78.9%) and complete remission was achieved in most cases (81.6%). CONCLUSIONS: Our epidemiological and clinicopathological findings relative to a large cohort of LABD patients are mostly consistent with the literature data. Interestingly, head, notably perioral, involvement and "string of pearls" arrangement occurred more frequently in the paediatric than adult group. The above clinical parameters may be regarded as diagnostic tools for LABD in children.

DNA damage in human skin fibroblasts from patients with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) and celiac disease (CD) are considered to be autoimmune diseases that share a specific trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not yet fully understood and no data are available regarding a possible role of fibroblasts in this disease. The aim of this study was to assess baseline DNA damage in fibroblasts in DH-diagnosed patients vs. fibroblasts of controls without DH or CD. Primary fibroblast cultures were derived from dermal biopsies from DH patients and controls (without DH or CD). In vitro genotoxic damage was investigated using the comet assay and ɣH2AX test after different treatments (with 33mer peptide and digested gliadin [DG]) in order to investigate a correlation between oxidative stress (evaluated by reactive oxygen species formation) and glutathione content. Our results demonstrate a difference in baseline DNA damage between cutaneous fibroblasts of controls and DH patients, moreover, DNA damage significantly increased after exposure to gluten (DG and 33mer peptide) in fibroblasts from DH patients. DNA damage in fibroblasts from patients under dapsone treatment was similar to that of the control group. Our data indicate that oxidative stress and DNA damage may be characteristics of fibroblasts from DH patients who are not treated with dapsone, particularly after exposure to gliadin peptides.

Cheilitis granulomatosa associated with lupus erythematosus discoid and treated with methotrexate: report of a case.

We present the rare case of a 47-year-old patient, suffering from cheilitis granulomatosa and lupus erythematosus discoid: this association is really exceptional because only once reported in English literature. In addition, the treatment of cheilitis granulomatosa is a challenge for the dermatologist: the gold standard, represented by steroids, is in fact designed as a short-time option. Our report confirms the good efficacy of methotrexate as a steroid-sparing agent.