Netherton syndrome (NS) is a rare and potentially life-threatening genetic skin disease responsible for skin inflammation and scaling, hair abnormalities and severe allergic manifestations. NS is caused by loss-of-function variants in Serine Peptidase Inhibitor Kazal-Type 5 (SPINK5), encoding the serine protease inhibitor LEKTI. NS patients have a profound skin barrier defect caused by unopposed kallikrein-related proteases activity (KLKs). They develop severe skin inflammation with eczematous-like lesions and high serum IgE levels. Multiomics studies have revealed that the IL-17/IL-36 pathway is the most predominant upregulated pathway in NS. It is associated with a Th2 signature with complement activation in the ichthyosis linearis circumflexa subtype, and with interferon and Th9 activation in the scaly erythrodermic form. Several case reports proved the efficacy of different biotherapies targeting IL-17A, IL-12/IL-23, IL-4R and IL-13R, TNF-a and IL-1β in pediatric NS patients. Intravenous immunoglobulins (IVIG) have also shown efficacy. These studies showed no severe side effects. At present, IL-17 blockade seems to be the most efficient treatment, but case reports remain limited with small numbers of patients and no placebo-control. Additional pathways must also be explored, and more efficient strategies could be used to block IL-17 and IL-23 pathways. In the future, the combination of specific strategies aiming at repairing the initial skin barrier defect could potentiate the efficacy of biologics. The current reports suggest that biological therapy is safe and often effective at pediatric age. However, controlled clinical trials that include a larger number of patients need to be conducted to reach more reliable conclusions.

Infantile perianal pyramidal protrusion (IPPP) is a benign condition generally noted in childhood but may persist for several years. Dermoscopy may help to distinguish it from other conditions, particularly genital warts. We report six cases of IPPP and describe the dermoscopic features that will distinguish these lesions from verrucae.

Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children’s University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.

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protein loss of 4.5 g. The presentation indicated a nephrotic syndrome with systemic involvement; therefore, a renal biopsy was performed, and the findings were consistent with membranous nephropathy (Figure , C). Additional serologic studies showed positive rapid plasma reagin test and treponema pallidum hemagglutination test with a titer of 1:128 and 1:40 960, respectively.On further questioning, the patient admitted having unprotected sexual intercourse with multiple female partners before the development of the rash. Therefore, secondary syphilis-associated nephrotic syndrome was diagnosed. The patient was treated with a single intramuscular injection of 2.4 million units of penicillin G benzathine. The treatment led to recovery of renal function, remission of nephrotic syndrome, and complete resolution of the skin eruptions.Syphilis is a well-known sexually transmitted disease caused by Treponema pallidum. 1 The sign of Biett collarette (Figure , A), which is characterized by a central maculopapule encircled by a white ring of scales, appears to be pathognomonic for secondary syphilis. 2 Nephrotic syndrome is a rare complication of acquired syphilis. 3 Membranous nephropathy is the most common pathologic finding. 4 Antisyphilis therapy will result in complete resolution of the renal manifestations. Our case highlights the importance of maintaining a high index of suspicion for secondary syphilis when evaluating teenagers with nephrotic syndrome. n