Paediatric cutaneous lymphomas including rare subtypes: A 40-year experience at a tertiary referral centre.

BACKGROUND: Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. OBJECTIVES: To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. METHODS: Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan. RESULTS: A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large-cell lymphomas (n = 5), primary cutaneous marginal zone B-cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis-like T-cell lymphomas (n = 2), primary cutaneous peripheral T-cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B-lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow-up data covering a median of 70.8 months (range 1-324) were available for 74 patients, of whom three died due to cutaneous lymphoma. CONCLUSIONS: Our findings shed light on the peculiar aspects and long-term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger-scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis.

Intrauterine big toenail imprints: A new cause of congenital skin dimples.

Congenital skin dimples (SD) are small cutaneous depressions that can be noted on any part of the body and may be caused by traumatic, mechanical, metabolic, and genetic factors as well as by exposure to infections or drugs. We describe 3 cases of unrelated healthy newborns displaying SD and discuss as a possible explanation the persistent friction of the big toenail onto the immature skin of the fetus during intrauterine life causing as depression in the skin.

Effectiveness and Safety of Acitretin in Children with Plaque Psoriasis: A Multicenter Retrospective Analysis.

BACKGROUND: Acitretin is licensed for and is most commonly used to treat psoriasis. Little information exists about its efficacy and safety in childhood and adolescent psoriasis. METHODS: Retrospective analysis of a group of children and adolescents (<17 years of age) with moderate to severe plaque psoriasis treated with acitretin between 2010 and 2014 at Italian dermatology clinics. Patients were identified through databases or registries. RESULTS: The study population consisted of 18 patients with a median age of 9.5 years at the start of therapy. The median maintenance dosage per day was 0.41 mg/kg. Eight patients (44.4%) achieved complete clearance or good improvement of their psoriasis, defined as improvement from baseline of 75% or more on the Psoriasis Area and Severity Index at week 16. Three had three or more courses of treatment with short disease-free intervals. In three patients, acitretin treatment was ongoing at the time of data collection. The mean total duration of treatment in responders was 22.7 months. One patient discontinued treatment because of arthralgia. The remaining nine patients (50%) discontinued treatment because it was ineffective. Mucocutaneous adverse effects occurred in all patients, but did not affect therapy maintenance. CONCLUSIONS: In this retrospective case series, acitretin was a moderately effective, well-tolerated treatment in children with moderate to severe plaque psoriasis. Given the small number of patients, statements about long-term safety are not possible.

Extensive and Persistent Dermal Melanocytosis in a Male Carrier of Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome): A Case Report.

Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an oval blue-grey macule or macules, commonly located on the lumbosacral area. In rare DM cases, when presenting with diffuse macules persisting during the first years of life, it could represent a cutaneous feature of mucopolysaccharidoses (MPS). Extensive congenital DM is actually associated with Hurler syndrome (MPS type I) and Hunter syndrome (MPS type II), although several reports also described this association with MPS type VI and other lysosomal storage disorders (LySD), including GM1 gangliosidosis, mucolipidosis, Sandhoff disease, and Niemann-Pick disease. Here, we present the case of a two-year-old boy presenting with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch, harboring a heterozygous variant of uncertain significance, NM_152419.3: c.493C>T (p.Pro165Ser), in the exon 4 of HGSNAT gene, whose mutations are classically associated with MPS IIIC, also known as Sanfilippo syndrome. This is the first report that highlights the association between extensive congenital DM and MPS type IIIC, as well as a pathogenetic link between heterozygous LySD carrier status and congenital DM. We speculate that some cases of extensive congenital DM could be related to heterozygous LySD carriers, as a manifestation of a mild clinical phenotype.

Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed "drug-induced PG." In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.

Infantile digital fibromatosis: a rare tumour of infancy. Report of five cases.

Infantile digital fibromatosis (IDF) is a rare tumour of infancy with a typical clinical presentation and characteristic histopathological findings. Despite an alarming appearance, IDF does not cause deep infiltration or metastasis. The traditional approach of surgical resection was recently challenged by increasing evidence of self regression in months or years. We describe the clinical history of five patients with IDF that were followed in our departments for 5 years.

Rare and common manifestations of COVID-19 in children.

Introduction: It has been almost 2 years since the first reports on cutaneous manifestations of COVID-19. Those reported in children are different and include macular, papular, lichenoid, vesicular, urticarial, and vascular morphologies, among others. The prognosis of isolated cutaneous involvement in COVID-19 in children is usually self-limiting but the extreme variety of clinical presentations complicates the clinical approach. Methods: Numerous reviews have been systematically drafted and edited giving the clinicians a future direction for skin presentations during pandemics. Results and Discussion: Hereby we report the rare and common manifestations of COVID-19 in children and question the recurrence phenomena and age-related distribution of the eruptions.

Henoch-Schönlein purpura following COVID-19 vaccine in a child: a case report.

BACKGROUND: Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis, typical of childhood. It's a self-limiting disease and it affects different systems. HSP is characterized by dermatological, abdominal, joint and renal clinical manifestations. This condition usually occurs upon infections, mainly upper respiratory tract ones, medications, vaccinations and malignancies. CASE PRESENTATION: We describe the case of a 11 year-old girl who developed a urticarial rash 12 days after the first dose of Pfizer-BioNTech BNT16B2b2 mRNA vaccine and a clear picture of Henoch Schönlein purpura 5 days after administration of the second dose of the same vaccine. CONCLUSION: To our knowledge, this is the first description of a pediatric patient with Henoch-Schönlein purpura occurring in association with vaccination against COVID-19.

Diffuse normolipemic plane xanthoma in a child with common variable immunodeficiency.

Diffuse plane xanthoma is extremely rare in children. Although it may be associated with systemic disorders, its etiology remains obscure in a number of patients. The case of a boy with common variable immunodeficiency and normal serum lipid levels, who developed diffuse plane xanthoma during treatment with intravenous immunoglobulins, is reported.

A retrospective study on clinical subtypes and management of morphea in 10 Italian Dermatological Units.

BACKGROUND: There are still few dermatological studies on morphea. We evaluated the epidemiological and clinical features and management of pediatric morphea, reporting dermatologists experience. METHODS: A multicenter retrospective observational study was carried out on the epidemiological and clinical features and management of the disease between 01/01/2009 and 01/10/2014 in 10 Italian Dermatological Units. RESULTS: We collected the data of 69 children affected by: circumscribed morphea (39.1%); linear morphea of trunk and limbs (14.5%); en coupe de sabre morphea (ECDS) (14.5%); progressive facial hemiatrophy (8.7%); generalized form (18.8%); mixed morphea (4.4%). The mean age at onset was 6.86±3.21 years, mainly between 2 and 8 years, but is statistically significantly lower for ECDS (4.5±3.03). Localizations were: head/neck (30.4%), limbs (26.1%), trunk (14.5%), 2 or more sites (29%), most often the trunk plus limbs. Extracutaneous manifestations were observed in 26.1% patients. 10 patients presented a second autoimmune disorder. Treatments were topical in 26.1% cases and systemic (alone or associated with topical treatments) in 68.1%. CONCLUSIONS: There was a lack of uniformity in the management of patients and an increasing awareness of dermatologists on the use of systemic therapies, in particular of methotrexate, which is no longer exclusive to rheumatologists. Methotrexate causes stabilization and improvement of the clinical signs, but topical creams are still considered adjuvant or maintenance therapies during/after the use of systemic drugs.

"Hairy" granular cell tumor.

The occurrence of a solitary subcutaneous granular cell tumor characterized by overlying hypertrichosis in a child is reported. Granular cell tumor should be included in the differential diagnosis of cutaneous neoplasms associated hypertrichosis in the pediatric patient.

Hypertrophic scarring is the usual outcome of non-membranous aplasia cutis of the scalp.

The outcome of aplasia cutis congenita of the scalp, nonmembranous type, in a series of 21 Caucasian patients is reported. In all the patients the congenital skin defect healed with irregular hypertrophic scar formation.

Single-plaque vegetating bromoderma.

Potassium bromide is still in use for the treatment of multidrug-resistant seizures. It is a known cause of severe drug-induced skin disorders. The clinical presentation of bromoderma may be similar to that of pyoderma gangrenosum when occurring with a single lesion. The case of a young girl with a single vegetating plaque of bromoderma on the leg is reported. The presence of pustules at the periphery of the plaque provides the clinical clue to the diagnosis.

Nasal dermoid sinus cyst.

Midline congenital abnormalities of the skin may be related to subjacent visceral developmental defects. We report on three unrelated children presenting a small midline pit on the bridge of the nose from which a small tuft of hair was emerging. This presentation is the hallmark of a nasal dermoid sinus cyst. In one of the patients the sinus tract was connected to the anterior cerebral fossa and required neurosurgical management. Although midline cutaneous abnormalities may look trivial, dermatologists should keep a high index of suspicion for possible association with more severe underlying defect. The diagnosis of nasal dermoid sinus cyst requires appropriate imaging studies to determine the extension of the sinus tract thus allowing proper management.

Treatment patterns with systemic antipsoriatic agents in childhood psoriasis: an Italian database analysis.

BACKGROUND: The majority of available systemic therapies have never been systematically investigated in moderate to severe childhood plaque psoriasis. For this reason, treatment preferences for moderate to severe psoriasis in childhood are still unknown. The aim of this study was to investigate the systemic treatment patterns of moderate to severe psoriasis in children and adolescents aged 18 or older in Italy. Additional secondary outcomes were duration of treatment and reasons for discontinuation. METHODS: In order to define differences in treatment patterns, we performed a chart review of all consecutive patients treated with systemic drugs during an index period of 5 years. Consecutive sampling of all patients with psoriasis aged ≤18 years, who had been treated with at least one systemic drug over a 5-year period, was made. RESULTS: The records of 58 consecutive patients, 27 males, 31 females. with moderate to severe psoriasis treated with at least one systemic therapy were reviewed. The median age (standard deviation) at the start of the first systemic treatment was 11.7±3.7 years. The most preferred first-line systemic treatment was cyclosporine, which was administered as first systemic treatment in 53.4% of patients, followed by acitretin in 22.4% of patients, etanercept and PUVA respectively in 8.6%, methotrexate in 6.8%. 48.2% of patients received a second systemic treatment due to inefficacy or side effects of the first-line therapy during the index period. Because of the small sample, and voluntary contribution, selection bias may have occurred. CONCLUSIONS: A considerable variation in the management of the first-line systemic therapy in children with moderate to severe psoriasis was observed. Cyclosporine was most commonly preferred as a first-line treatment. The availability of new therapeutic agents could change the scenario of treatment patterns in childhood psoriasis.

Juvenile gangrenous vasculitis of the scrotum: Is it a variant of pyoderma gangrenosum?

Juvenile gangrenous vasculitis of the scrotum was described by Piñol et al in 1974 as a unique variant of scrotal gangrene of unknown origin, occurring exclusively in young individuals. It was characterized by an acute onset of skin ulcers undergoing complete resolution after appropriate therapy, with no relapses. We present a typical case of this extremely rare disease affecting a 16-year-old boy in whom the scrotal ulcerations were preceded by an episode of pharyngitis with fever. The condition promptly regressed after administration of intramuscular betamethasone in combination with oral ciprofloxacin. According to Piñol et al, juvenile gangrenous vasculitis of the scrotum, although poorly known to dermatologists, should be regarded as a distinctive entity within the wide group of scrotal gangrenes. On the other hand, the hypothesis that this condition may well represent a variant of pyoderma gangrenosum is discussed.

Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response.

Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. We investigated the presence of KIT(M541L) in five males with chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), all negative for Platelet-derived growth factor-alpha (PDGFR) or PDGFRbeta abnormalities, which responded to imatinib therapy. To assess whether the mutation was constitutive or somatic in nature, we evaluated its presence analyzing either the neoplastic or normal cell population (epidermal cells or CD3-positive T lymphocytes). KIT(M541L) substitution was found in 4 out of 5 patients and in all it was somatic in nature. All patients were treated with low dose imatinib (100 mg daily orally), achieving complete and persistent clinical and hematological remission (median follow-up 74 months). One patient relapsed after 50 months. Our study strongly suggests to search for the KIT(M541L) in patients with CEL, NOS, negative for PDGFRalpha and PDGFRbeta abnormalities, to identify a subgroup of cases who may benefit from low dose imatinib therapy.