Improvement of self-administration experience with a new injection device: Real-life experience with risankizumab in patients with psoriasis.

BACKGROUND: Trypanophobia or "needle phobia" represents a potential hindrance to the effective management of chronic diseases whenever an injectable therapy might be required, especially in case of frequent administrations. Psoriasis, a chronic dermatologic disease, can be effectively treated with biologic drugs administered subcutaneously. Thankfully, anti-IL-23 drugs require few administrations per year and are available in prefilled pens that hide the needle, thus representing a convenient option in patients with trypanophobia. METHODS: An observational multicentric study was conducted on patients with moderate-to-severe psoriasis who were treated with 75 mg × 2 risankizumab prefilled syringe therapy for more than 6 months and reported a loss of efficacy measured by the Psoriasis Area and Severity Index (PASI) from PASI 90 to PASI 75 attributed to a reduction of adherence due to trypanophobia. The patients were switched to 1 prefilled pen of risankizumab 150 mg and asked to fill out the Self-Injection Assessment Questionnaire (SIAQ) before and after the injection at week 0 and at the following administration after 12 weeks. Subjects scored each item of the SIAQ on a 5-point scale, scores were later transformed from 0 (worst experience) to 10 (best experience). RESULTS: Twenty-two patients were enrolled. The mean SIAQ predose domain scores were 5.5 for feelings about injection, 6.2 for self-confidence, and 6.4 for satisfaction with self-injection. After dose scores were higher (> 8.5) for each of the six domains at Week 0 and even higher after 12 weeks (> 9.0). CONCLUSIONS: User-friendly devices, such as prefilled pens, and a lower number of injections improved patient satisfaction in a group of patients with psoriasis on treatment with biologic drugs. We believe that treatment adherence could be positively influenced by such changes in the way of administration of a biologic treatment.

Clinicopathologic and Dermoscopic Features of 20 Cases of Spark's Nevus, a Dermoscopic Simulator of Melanoma.

ABSTRACT: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma.

Recent advances in palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris. The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP. In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1ß, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP. Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.

Mycobacterium kansasii infection in a psoriasis patient treated with adalimumab and switch to apremilast: First report and literature review.

Patient under anti-TNF-alpha treatment have an increased risk of mycobacterial infections, particularly tuberculosis. Only four case reports of Mycobacterium kansasii infection under anti-TNF-α treatment (two with etanercept, two with infliximab) have been reported, but none under adalimumab. A 72-year-old man treated with adalimumab for psoriasis vulgaris and arthropathic psoriasis, complained on nocturnal cough, occasional hemoptysis and the new onset of ill-defined, reddish, asymptomatic persistent plaques-nodules covered by serum crusts on his back, on the dorsum of the right hand and right middle finger. Routine laboratory investigations, HIV and TB screening (QuantiFERON-TB-Gold test) were all within normal limits. A skin biopsy was inconclusive and special staining resulted negative for microorganisms. Only PCR identified M. kansasii. The patient stopped adalimumab and started anti-TB treatment with gradual improvement of the skin lesions. At 26 months follow-up visit no signs or symptoms of relapse of M. kansasii disease occurred.

Teledermatologic monitoring for chronic cutaneous autoimmune diseases with smartworking during COVID-19 emergency in a tertiary center in Italy.

Because of the coronavirus disease 2019 (COVID-19) emergency, on March 9, 2020 Italy went in lock-down imposing the closure of non-urgent outpatient clinics devoted to care of chronic, severe, inflammatory skin diseases that require periodic follow-up. In this emergency situation, due to the lack of a teledermatology platform and in order not to leave our vulnerable high-need patients without proper follow-up, we started a teledermatologic service in smartworking using phone calls and emails. The total number of patients scheduled was 195; in 12 cases, we were not able to talk to the patients. Remote monitoring was performed in 183 patients (126 moderate to severe psoriasis, 10 severe acne, 11 severe atopic dermatitis, 11 hidradenitis suppurativa, 9 blistering autoimmune diseases, and 16 other autoimmune skin diseases). During remote-visits, several interventions were conducted: triage for COVID-19 suspected symptoms, email check of clinical pictures and of laboratory examinations, advices for topical and systemic therapy continuation or discontinuation/switch and reschedule of next appointment. Only five patients required personal office visit (2.7%), reducing consistently the number of face-to face visits. Our real-life experience shows that remote monitoring was effective in preventing unnecessary worsening of severe chronic skin diseases and poor outcomes due to withdrawal of current therapy.

Update on the pathogenesis of Scleroderma: focus on circulating progenitor cells.

In systemic sclerosis (SSc), the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs) might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14 (+) cells) and probably correspond to a different degree of differentiation of a single cell of origin. Several subsets of CPCs have been described in patients with SSc, all have a monocytic origin but may or may not express CD14, and all of these cells have the ability to give origin to endothelial cells, or collagen (Col)-producing cells, or both. We were able to identify six subsets of CPCs: pluripotent stem cells (CD14 (+), CD45 (+), and CD34 (+)), monocyte-derived multipotential cells (MOMCs) or monocyte-derived mesenchymal progenitors (CD14 (+), CD45 (+), CD34 (+), Col I (+), CD11b (+), CD68 (+), CD105 (+), and VEGFR1 (+)), early endothelial progenitor cells (EPCs) or monocytic pro-angiogenic hematopoietic cells or circulating hematopoietic cells (CD14 (+), CD45 (+), CD34 (low/-), VEGFR2 (+/-), CXCR4 (+), c-kit (+), and DC117 (+)), late EPCs (CD14 (-), CD133 (+), VEGFR2 (+), CD144 (+) [VE-cadherin (+)], and CD146 (+)), fibroblast-like cells (FLCs)/circulating Col-producing monocytes (CD14 (+), CD45 (+), CD34 (+/-), and Col I (+)), and fibrocytes (CD14 (-), CD45 (+), CD34 (+), Col I (+), and CXCR4 (+)). It has been demonstrated that circulating CD14 (+) monocytes with an activated phenotype are increased in patients with SSc when compared with normal subjects. CD14 (+), CD34 (+), and Col I (+) spindle-shaped cells have been found in increased numbers in lungs of SSc patients with interstitial lung disease. Elevated blood amounts of early EPCs have been found in patients with SSc by different groups of researchers and such levels correlate directly with the interstitial lung involvement. The prevalence of hematopoietic markers expressed by CPCs that migrate from blood into injury sites in SSc differs and changes according to the degree of differentiation. CXCR4 is the most commonly expressed marker, followed by CD34 and CD45 at an end stage of differentiation. Such difference also indicates a continuous process of cell differentiation that might relate to the SSc clinical phenotype (degree of fibrosis and vascular involvement). A deeper understanding of the role of each subtype of CPCs in the development of the disease will help us to better classify patients in order to offer them targeted approaches in the future.

New onset of dermatomyositis/polymyositis during anti-TNF-α therapies: a systematic literature review.

We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM) in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA), one by Crohn's disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD) were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors) was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA) with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.

Fast growing penis ulcer: an unusual coincidence.

A 57-year-old man was seen with a 2-week history of progressive enlargement of an asymptomatic genital ulcer associated with bilateral inguinal lymphadenomegaly. Multiple unprotected heterosexual contacts were reported. The family doctor misdiagnosed primary syphilis with the following laboratory results: negative findings on the Venereal Disease Research Laboratory test, positive findings on the Treponema pallidum particle agglutination assay (titer 1:1280), and IgM negative on the Treponema pallidum particle agglutination assay. The patient was treated with penicillin G for the diagnosis of indeterminate latent syphilis and initially denied authorization for a skin biopsy. After 2 weeks, fast enlargement of the lesion was documented. He underwent skin biopsy, and the histopathologic examination revealed squamous cell carcinoma, and polymerase chain reaction for human papillomavirus 16 was positive.