Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate-to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region.

INTRODUCTION: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. OBJECTIVES: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. METHODS: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant'Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell'Immacolata - IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. RESULTS: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Dermatology Life Quality Index score. CONCLUSIONS: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported.

Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study.

BACKGROUND: The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET). METHODS: IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively. RESULTS: 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached. CONCLUSION: The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.

Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic-pituitary-thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.

Deep Sequencing of Immunoglobulin Genes Identifies a Very Low Percentage of Monoclonal B Cells in Primary Cutaneous Marginal Zone Lymphomas with CD30-Positive Hodgkin/Reed-Sternberg-like Cells.

The spectrum of cutaneous CD30-positive lymphoproliferative disorders encompasses both inflammatory and neoplastic conditions. CD30+ Hodgkin and Reed-Sternberg-like cells have been occasionally reported in primary cutaneous marginal zone lymphoma, where they are thought to represent a side neoplastic component within a dominant background of lymphomatous small B cells. Herein, we describe the histological and molecular findings of three cases of primary cutaneous marginal zone lymphomas with CD30+ H/RS cells, in which next-generation sequencing analysis revealed the clonal population to consist in less than 5% of the cutaneous B-cell infiltrate, providing a thought-provoking focus on a possible main role for CD30+ cells in primary cutaneous marginal zone lymphoproliferations.

Vitiligo with Progressive Repigmentation during Secukinumab Treatment in a Patient with Psoriatic Arthritis: A Case Report.

The proposed role of interleukin (IL)-17 in vitiligo pathogenesis, as well as the possible action of anti-IL-17A drugs on vitiligo, are not fully understood. The appearance of vitiligo as a paradoxical effect of treatment with anti-tumor necrosis factor-α drugs is an event well known in the literature, but is rarely described with anti-IL-17A drugs. In this case report, we describe a 42-year-old woman who developed new-onset vitiligo with repigmentation during successful secukinumab therapy for psoriatic arthritis. After 1 year of secukinumab therapy, vitiligo affecting >85% of the skin was evident on clinical and dermatoscopic examination, together with small, repigmented lesions. In depigmented lesions, reflectance confocal microscopy (RCM) showed disappearance of the bright dermal papillary rings normally seen at the dermo-epidermal junction. In repigmented lesions, activated dendritic melanocytes were observed on RCM. The patient continued to receive secukinumab, and continued to experience a slow and progressive repigmentation. Our case shows that anti-IL-17A biological agents for chronic inflammatory diseases may be associated with the development of new-onset vitiligo that improves over time with ongoing therapy. Therefore, physicians should be aware of the possibility of this rare paradoxical skin reaction in patients receiving secukinumab, and that it may not be necessary to discontinue secukinumab to achieve repigmentation.

May Bacterial Infections Trigger Bullous Pemphigoid? Case Report and Review of Literature.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease, mainly observed in the elderly. Infections have been suggested as possible disease triggers. However, infections may even heavily influence the disease clinical course and mortality. A 75-year-old woman was admitted to hospital for severe erythematosus blistering disease, accompanied by hyper-eosinophilia and hyper-IgE. The culture of bullous fluid was positive for Enterococcus faecalis, the blood culture was positive for Staphylococcus aureus, and the urine culture was positive for Proteus mirabilis and Escherichia coli. Moreover, circulating anti-BP180 IgG was present and the histopathological/ultrastructural examination of a lesional skin biopsy was compatible with BP. High eosinophil levels (up to 3170/µL) were found throughout the clinical course, while values below 1000/µL were associated with clinical improvement. The total IgE was 1273 IU/mL, and specific anti-G/V-penicillin/ampicillin IgE antibodies were positive. The patient had a complete clinical recovery in two months with methyl-prednisolone (40 then 20 mg/day) and low-dose azathioprine (50 mg/day) as a steroid-sparing agent. The steroid treatment was tapered until interruption during a one-year period and intravenous immunoglobulins have been administered for three years in order for azathioprine to also be interrupted. The patient stopped any treatment five years ago and, in this period, has always been in good health. In this case, the contemporaneous onset of different bacterial infections and BP is suggestive of bacterial infections acting as BP trigger(s), with allergic and autoimmune pathways contributing to the disease pathogenesis.

Risk of Depression Associated With Finasteride Treatment.

BACKGROUND: Finasteride is one of several inhibitors of the 5α-reductase that converts testosterone to dihydrotestosterone used to treat hair loss and benign prostatic enlargement. Emerging clinical observations indicate that such treatment may be associated with depression, anxiety, and possibly increased suicidal risks, in addition to sexual dysfunction, even after its discontinuation. METHODS: We carried out a systematic review of reports pertaining to association of finasteride treatment with clinical depression or other adverse psychiatric effects. We analyzed reported risks of depression by pooling of rates and by meta-analysis of comparisons of subjects treated with finasteride or not. FINDINGS: Crude pooled rates of depressive symptoms with versus without finasteride were 3.33% (confidence interval, 3.22%-3.44%) versus 2.54% (2.44%-2.64%); random-effects meta-analysis yielded an odds ratio of 2.14 (1.40-3.27) (both P < 0.0001). In addition, risk of suicidal ideation or behavior was greater with versus without finasteride (21.2% [21.0%-21.5%] vs 14.0% [13.8%-14.2%], P < 0.0001), and risk of sustained sexual dysfunction was high (60.1% [37.3%-82.9%]). CONCLUSIONS: The findings support a growing impression that finasteride is associated with adverse psychiatric effects that can persist in association with sexual dysfunction after discontinuing finasteride treatment.

Multiple Sclerosis Treatment and Melanoma Development.

Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution.

Tridimensional Matryoshka Tattoo: An Important.

Dear Editor, Tattooing is a global and ancient practice that has endured until the present day. It was originally used to indicate religious beliefs, tribal affiliation, loyalty to a leader, or had a therapeutic function. Adverse reactions from tattooing are common, and cutaneous reactions to red pigment have been widely reported (1,2). Herein we report a case of a 30-year-old female patient admitted to our Department of Dermatology for a reaction to a tattoo localized at the violet and black areas of the tattoo on the upper part of her left leg. The patient reported that the tattoo had been made two years earlier, but the cutaneous alterations appeared after she decided to change the color from pink to violet. On physical examination, multiple erythematous nodular itching lesions were present at the areas of the tattoo in which the violet and black color were used (Figure 1). She had undergone antibiotic therapy without resolution after which topical corticosteroids were applied with temporary remission of signs and symptoms. Personal and familial medical history were negative. The patient reported a jewelry allergy that had never been investigated. Based on the suspicion of an allergic reaction we decided to execute a patch test SIDAPA series and patch test special tattoo series (copper sulfate 1% water, dimetilaminoazobenzene-p 1%, aminoazotoluene-o 1%, blue scattered 3 1%, blue scattered 124 1%, yellow scattered 3 1%, orange scattered 3 1%, red scattered 1 1%, gentian violet 2%, cadmium chloride 1% in water, nickel sulphate 5%, iron chloride 2% in water, potassium dichromate 0.5%, chromium trichloride 2%, aminoazobenzene-p 0.25%, cobalt chloride 1%, aluminum chloride 2%, titanium dioxide 0.1%, zinc 2.5%, mercury chloride 0.05% in water, kathon cg 0.01% in water, phenol 0.5%, ethylenediamine hydrochloride1%, phenylenediamine base-p 1%, formaldehyde 1% in water, phthalic anhydride 1%, rosin 20%, dibutyl phthalate 5%, hexamethylenetetramine 1%, benzophenone 5%). Both series of patch test showed positivity for nickel sulfate 5% at 48 hours (++) and 72 hours (+++). We then performed a 4 mm punch biopsy of the nodular lesions localized at the black and violet areas. The histological examination revealed dermal sclerosis characterized by inflammatory reaction with lympho-mononuclear infiltration in the perivasal zone. Macrophages with red and black pigment were present. The histological pattern was compatible with a granulomatous reaction. Tattooing can result in a wide variety of complications, whose prevalence and incidence still remain unclear. Some authors (3) classify such cutaneous complications in various ways, such as according to: - the length of their evolution: acute and chronic reactions; - the delay of onset after tattooing: early - during the healing phase - or delayed - after tattoo healing; - the type of reaction: infection, hypersensitivity reaction, etc. The practice of tattooing may have local or systemic complications. Dermatoses such as psoriasis, systemic erythematous lupus, sarcoidosis, lichen planus, and pseudo-epitheliomatous hyperplasia can be localized in the area of the tattoo, but allergic sensitivity to one of the pigments is the most frequent cause of dermatological reactions in the site of tattoo (4,5). In fact, adverse reactions to tattoo pigments, especially the red one, are well-described in literature. Furthermore, these compounds frequently contain components which are not systematically characterized. In our case, the granulomatous reaction did not correspond to an allergic reaction to the pigment. In fact, the patch test was negative for all pigments investigated, only showing a positive result for nickel sulfate. However, the specific and well-defined localization of the nodular lesions on the black and violet areas led us to hypothesize that the tattoo pigments in these areas contained some unknown component causing the reaction. In our opinion, a possible explanation could be that the new pigment that had been used contained a small amount of nickel sulfate, which caused the granulomatous reaction. In conclusion, we presented this clinical case to emphasize the widespread incidence of tattoo-related adverse effects, which are mostly caused by red pigment. Dermatologists should constantly strive familiarize themselves with current research on this practice and its complications. On the other hand, people with potential risk factors for adverse reactions should refer to a specialist before getting tattoos. Tattooists should use a checklist and informed consent to screen people with such potential risk factors. Furthermore, it is necessary to perform additional studies concerning ink and pigment components, with the aim of systemically characterizing the substances used in tattoos. Lastly, as emphasized by our case, patients at risk should referred to the dermatologist not only before getting a new tattoo but also in case of color changes in a pre-existing tattoo.

PsA-Disk, a novel visual instrument to evaluate psoriatic arthritis in psoriatic patients: an Italian derma-rheuma multicentre study.

BACKGROUND: Consensus among dermatologists and rheumatologists in the diagnosis and assessment of musculoskeletal diseases in psoriasis (PsO) patients is needed. This study assesses characteristics of musculoskeletal pain in patients with PsO for the presence of psoriatic arthritis (PsA) and evaluation of a novel 16-item visual instrument (PsA-Disk). METHODS: Data were collected from eight dermatological/rheumatological centres across Italy. Patients with PsO completed PEST (Psoriasis Epidemiology Screening Tool) and PsA-Disk questionnaires during the first visit. A rheumatological visit was performed to confirm the presence of PsA. Both validity and reliability of PsA-Disk were assessed. RESULTS: A total of 573 patients with PsO were examined at the first visit, and 120 (21%) were diagnosed with PsA. Patients with PsA compared with patients with PsO (n = 119) presented statistically significant differences for: nail involvement, PEST score ⩾3, higher erythrocyte sedimentation rate (ESR), Nail Psoriasis Severity Index (NAPSI)-feet, NAPSI-(hands + feet) and PsA-Disk scores (73.9 ± 32.1 versus 58.1 ± 39.8, p < 0.001). Patients with PsA with knee arthritis had higher PsA-Disk scores (98.4 ± 26 versus 71.5 ± 31.9, p = 0.006) that were also correlated with number of swollen (r = 0.2, p < 0.05) and tender joints (r = 0.24, p = 0.021), patient (r = 0.4, p < 0.001) and physician-pain-visual analogue scale (VAS; r = 0.33, p < 0.001), patient global assessment (PGA)-VAS (r = 0.23, p = 0.025), physician-health assessment questionnaire (HAQ; r = 0.38, p = 0.011), Disease Activity Score (DAS)-44 (r = 0.25, p = 0.023) and Disease Activity in Psoriatic Arthritis (DAPSA; r = 0.31, p = 0.005). The instrument had excellent reliability in terms of internal consistency (Cronbach's alpha = 0.90) and stability (intraclass correlation = 0.98). Moderate agreement between PsA-Disk and PEST (Cohen's kappa = 0.46) was observed, while construct validity appeared appropriate [PsA + patients: PsA-Disk score (interquartile range; IQR) =71 (50-96); PsA-patients: PsA-Disk score (IQR)=50 (20-90); p < 0.001]. CONCLUSION: PsA-Disk may be considered a valid novel instrument aiding both dermatologists and rheumatologists in the rapid detection and assessment of musculoskeletal disease characteristics.

Vitiligo and Autoimmune Thyroid Disorders.

Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves' disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).