FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

Localized pemphigus vulgaris on scalp: an atypical presentation.

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.

Atypical pediatric presentation of alopecic and aseptic nodules of the scalp with features of dissecting cellulitis.

Alopecic and aseptic nodules of the scalp (AANS) and dissecting cellulitis of the scalp (DCS) are rare, closely related conditions of young men that exclusively affect the hair-bearing scalp. We describe a 9-year-old boy who presented with a 6-year history of chronically relapsing, sterile, partially scarring nodules of the scalp and facial skin. Histopathology revealed mixed inflammatory infiltrates consisting of neutrophils, macrophages, lymphocytes, and plasma cells in the deep dermis, consistent with the morphological pattern of suppurative, partly granulomatous dermatitis. The present atypical case is characterized by prepubertal onset and facial involvement which, to our knowledge, has not yet been described before, may be included in the spectrum of "typical" AANS and "typical" DCS.

A novel DLL4 mutation in Adams-Oliver syndrome with absence of the right pulmonary artery in newborn.

Adams-Oliver syndrome (AOS), a rare inherited disorder, is characterized by scalp and terminal limb defects. Several genes associated with Notch pathway mutations have led to AOS. Here, we report a Thai male newborn presenting with aplasia cutis congenita and absence of a right pulmonary artery, which is suggestive of AOS. This was confirmed by the identification of a novel missense mutation in DLL4, a heterozygous one base pair change at nucleotide 82 (c.82G>C, p.Gly28Arg), which is in N-terminal domain. This is the first DLL4-related AOS case with arterial defect.

Cutaneous squamous cell carcinoma in an autosomal-recessive Adams-Oliver syndrome patient with a novel frameshift pathogenic variant in the EOGT gene.

Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.

Therapeutic options for perifolliculitis capitis abscedens et suffodens: A review.

Perifolliculitis capitis abscedens et suffodiens (PCAS) is a chronic skin inflammatory disease characterized by relapsing folliculitis and painful, fluctuant abscesses, sinus tracts, and scars. The treatment of PCAS is challenging and clinical practice varies a lot, and how to choose the best treatment for PCAS is a real problem for clinicians. We reviewed articles providing treatment options for patients with PCAS in different databases. Dermatologists may find this review helpful to meet the challenges of PCAS management, but there is still a lack of authoritative guidelines. In the future, more robust randomized control trials are needed to determine the best treatment for PCAS.

Nonmelanoma skin cancer in the setting of erosive pustular dermatosis of the scalp: A case series and comment on management implications.

BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory cutaneous disorder typically affecting sun-damaged skin of mature individuals. Clinical features of EPDS include sterile pustules and chronic crusted erosions that can be hyperkeratotic and lead to scarring alopecia, atrophy, and telangiectasia. While the condition occurs on sun-damaged skin, a relationship with non-melanoma skin cancer (NMSC) has not been investigated. OBJECTIVES: Here we attempted to identify cases of NMSC developing in the setting of EPDS. METHODS: Retrospective review of EPDS cases in a dermatology practice. RESULTS: Six patients with mean (range) age 82 (65-92) years that developed NMSC in the setting of EPDS are reported. Five patients had skin phototype I or II associated with substantial solar elastosis. Four patients had history of NMSC. Four patients developed squamous cell carcinoma and two patients basal cell carcinoma on the scalp in the setting of EPDS. A morphologic change in an EPDS lesion, such as a crusted plaque becoming nodular and/or growing significantly within a relatively short period of time, prompted a biopsy that revealed NMSC. CONCLUSIONS: NMSC may develop in the setting of EPDS. Possible mechanisms underlying this association include the chronic inflammation associated with EPDS and ultraviolet light exposure. It is crucial to promptly obtain a biopsy in EPDS cases showing signs suspicious for NMSC. Further studies are required to confirm whether NMSC shows a higher prevalence in the setting of EPDS.

Localized alopecia with itching on the scalp.

We describe the use of trichoscopy to arrive at a diagnosis, and discuss the possible differential diagnoses in a patient presenting with localized itching and alopecia of the scalp.

Serum tryptase levels in patients with psoriasis: a pilot study for a possible useful biomarker.

In psoriasis, biomarkers for disease prognosis and response to treatment may help clinicians to improve patient management. Hence, we decided to evaluate the role of serum tryptase (ST) in a sample of patients with psoriasis. We found higher levels of ST in patients with scalp psoriasis than in those without (6.1 vs. 4.6 ng/mL), in those with palmoplantar psoriasis than in those without (5.3 vs. 5 ng/mL) and, with less significance, in those with psoriatic arthritis than in those without (6.1 vs. 5.1 ng/mL).

Trichoscopy may enhance the differential diagnosis of erythroderma.

There is a paucity of data concerning the usefulness of trichoscopy in patients with erythroderma. The aim of the study was to compare the trichoscopic features in erythroderma of various aetiologies. In total, 49 patients with a determined cause of erythroderma [including atopic dermatitis (AD), mycosis fungoides (MF), allergic contact eczema (ACE), psoriasis (Pso), Sézary syndrome (SS), drug reaction, pityriasis rubra pilaris (PRP), dermatomyositis (DM), actinic reticuloid (AR), crusted scabies (CS) and pemphigus foliaceus (PF)] were included in the study. Dotted vessels were present in patients with AD, PRP, MF, SS and Pso, and absent in DM, CS and PF (χ², P < 0.02). Spermatozoon-like vessels were observed only in MF and SS (P = 0.001). Whitish-pinkish structureless areas were described in all patients with DM, AR and CS (P < 0.03). The type of vessel and the presence of whitish-pinkish structureless areas under trichoscopy may indicate the cause of erythroderma.

Impact of a health educational interventional program on reducing the head lice infestation among pupils in an elementary school of a sub-tropical region: a quasi-experimental study.

BACKGROUND: Pediculosis is an important social challenge that can be caused by human head louse, Pediculus humanus capitis. This infestation is cosmopolitan, especially in countries with low hygiene and sanitation. Regular health education classes for students and their parents are required to reduce this infestation in schools and families. This study aimed to evaluate the impact of a health education intervention program on reducing head lice among pupils of an elementary school. METHODS: In a quasi-experimental study, a total of 880 elementary school girls were screened for pediculosis in (2017-2018). The prevalence of pediculosis follow-up continued monthly until the end of the school year after a two months educational intervention course. Visual inspection was applied for initial diagnosis of infection. The suspected cases were confirmed by wood lamp and potassium hydroxide (KOH) microscopic examination. Also eight questions about diagnostic, epidemiology, treatment and prevention were answered in a questionnaire by 50 volunteer parents before and after the training intervention course, to evaluate their general knowledge and measure the effectiveness of learning. All data were statistically analyzed using SPSS software (version 20.0, SPSS, Inc., Chicago, IL, USA). McNemar's test was also applied to investigate the prevalence rate before and after the intervention. A p -value of less than 0.05 was considered as statistically significant. RESULTS: At the beginning of study, pre-intervention prevalence of pediculosis among pupils was 8.4% (49/594). The mean age in all pupils was 9.86 ± 1.83 years old and the most infestation was shown in fourth-grade students with 10 years old. Analysis of statistics demonstrated a significant difference between having infestation and the number of members in the families. Post-intervention phase led to a decreased prevalence of pediculosis in pupils to 3% (8/594) (p-value < 0.05). Based on statistical analysis of questions before and after the training in the questionnaire, a significant increase of parental knowledge was observed on the prevention program of pediculosis (p-value < 0.001). CONCLUSION: The prevalence of pediculosis was significantly reduced following the educational interventions in the school. The applied interventions may be implemented in other residual centers to get rid of this important infestation.

An Up-to-Date Approach to the Management of Dissecting Cellulitis.

Dissecting cellulitis of the scalp (DCS) also known as perifolliculitis capitis abscedens et suffodiens (PCAS) is a chronic, relapsing, inflammatory dermatosis consisting of edematous sterile pustules and nodules resulting in sinus tracts and scarring alopecia. Although first described as infectious in 1903, DCS is primarily an inflammatory process that can precede a secondary infection; this is similarly true of the other conditions within the follicular occlusion tetrad: hidradenitis suppurativa (HS), acne conglobata, and pilonidal sinus.

Refractory Dissecting Cellulitis of the Scalp Treated With Risankizumab.

Perifolliculitis capitis abscedens et suffodiens or dissecting cellulitis (DC) is a rare and chronic disease with a predilection for the occipital, vertex, and parietal scalp. DC is characterized by multinodular lesions with purulent drainage and sinus tract formation. It is classically seen in middle-aged males of African descent. The etiology of the disease is unknown; however, leading theories suggest that stasis associated with follicular occlusion begets bacterial infection and follicular destruction with a subsequent granulomatous and neutrophilic response.1 This is supported by the suppurative nature of the disease and its association with acne conglobota, pilonidal cysts, and hidradenitis suppurativa. These conditions are thought to have a shared etiology and are also widely accepted as being due to follicular occlusion.1 The approach to treatment of DC is varied as there is no current consensus on management. We present the case of risankizumab, an IL-23 inhibitor, used to successfully treat DC. J Drugs Dermatol. 2022;21(3): doi:10.36849/JDD.6699.

Treatment of Scalp Psoriasis.

Scalp involvement is seen in a majority of individuals with psoriasis, a chronic autoimmune skin disease with variable phenotypes. Occasionally, isolated scalp involvement is observed; and this causes significant psychosocial morbidity. Management of scalp psoriasis is difficult, in part due to the difficulty of applying topical agents and its refractory nature. Various treatment options are available with variable efficacy. Topical agents include topical steroids, keratolytics, tar and anthralin compounds, vitamin D analogues, and vitamin A derivatives. The combination treatment of topical betamethasone and calcipotriene is the most effective topical therapy. Systemic agents include conventional agents such as methotrexate, cyclosporine, and oral retinoids. Biologics offer a greater efficacy, with near complete or complete clearance of the scalp. In this article we review the published literature on adult and scalp psoriasis to highlight its treatment. Articles published in peer-reviewed journals were included for qualitative analysis of the literature, including reviews, clinical trials, case series, case reports published in the electronic database (MEDLINE/PubMed) through June 2021, cross references of respective articles, and trials from clinicaltrials.gov. J Drugs Dermatol. 2022;21(8):833-837. doi:10.36849/JDD.6498.

Trichorhinophalangeal syndrome type II associated with aplasia cutis congenita in a neonate.

Aplasia cutis congenita (ACC) was diagnosed in a newborn with dysmorphic facial features, oligodactyly of the bilateral feet, and hip instability. The neonate's clinical abnormalities in addition to genetic testing confirmed a diagnosis of trichorhinophalangeal syndrome (TRPS) type II. The possibility of concurrent Adams-Oliver syndrome (AOS) is raised.

Scalp eschar and neck lymphadenopathy by Rickettsia slovaca after Dermacentor marginatus tick bite case report: multidisciplinary approach to a tick-borne disease.

BACKGROUND: Scalp Eschar and Neck LymphAdenopathy after Tick bite is a zoonotic non-pathogen-specific disease most commonly due to Rickettsia slovaca and Rickettsia raoultii. Diagnosis is mostly based only on epidemiological and clinical findings, without serological or molecular corroboration. We presented a clinical case in which diagnosis was supported by entomological identification and by R. slovaca DNA amplifications from the tick vector. CASE PRESENTATION: A 6-year-old child presented with asthenia, scalp eschar and supraclavicular and lateral-cervical lymphadenopathy. Scalp Eschar and Neck LymphAdenopathy After Tick bite syndrome following a Dermacentor marginatus bite was diagnosed. Serological test on serum revealed an IgG titer of 1:1024 against spotted fever group rickettsiae, polymerase chain reaction assays on tick identified Rickettsia slovaca. Patient was successfully treated with doxycycline for 10 days. CONCLUSIONS: A multidisciplinary approach including epidemiological information, clinical evaluations, entomological identification and molecular investigations on tick, enabled proper diagnosis and therapy.

Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review.

Scalp psoriasis represents the most common difficult-to-treat area in psoriasis patients. Its presence is linked to severe discomfort and impairment of quality of life given the associated symptoms (most of all, scaling and pruritus) and the location in a highly visible area, thus a prompt treatment is required. Its management may be challenging as the scalp is quite sensitive to long-term treatment with topical corticosteroids and usually resistant to topical and systemic agents. Likely, the currently available therapeutic armamentarium has been enriched with biologicals and small molecules that revolutionized psoriasis treatment and that of scalp psoriasis. Nevertheless, the lack of international dedicated guidelines pushed us to perform a comprehensive review on the efficacy and safety of biologics and small molecules on scalp psoriasis with the aim to put the basis for a therapeutic algorithm. After reviewing all the available evidence on the short-term and long-term efficacy of biologics and small molecules on scalp psoriasis the use of the newest biologics (anti-IL-17 and anti-IL-23) seems to be linked to the highest clinical performances in controlling scalp psoriasis. However, head-to-head comparisons between different biologics or biologics and small molecules are lacking. Hence, treatment selection should always be individualized.

Clinical and trichoscopic features in various forms of scalp psoriasis.

BACKGROUND: Scalp psoriasis is often undiagnosed or inadequately treated. The patient himself underestimates the seriousness of this hair disease and consults too late to a dermatologist. OBJECTIVES: The aim of our study was to create a correlation between the clinical patterns and trichoscopy of scalp psoriasis such in a way to help the clinician to make the diagnosis and select the appropriate therapy. MATERIAL AND METHODS: We gathered all patients affected of scalp psoriasis afferent to Outpatient's hair consultation of the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, from January 2012 to December 2018. All patients were evaluated through clinical, trichoscopic examination and a skin biopsy only in doubtful cases. We quantified the severity of the disease with several objective and subjective parameters every 4 months, up to 1 year. We recorded therapies, outcome data and quality of life. RESULTS: We collected 156 patients affected by scalp psoriasis, identifying seven clinical patterns with specific trichoscopical correlation. In the order of frequency, the clinical patterns were as follows: plaque psoriasis (with a prevalence of erythema, silver-white scales and twisted red loops vessels and red dots); thin scales (with silvery-white scales, simple red lines and signet red ring vessels); sebopsoriasis (with greasy scales, erythema with red dots, globules and twisted and bushy red loops at high magnification); psoriatic cap (with silver-white scales, erythema and polymorphic vascular pattern); pityriasis amiantacea (with yellowish adherent scales, erythema and simple red loops capillaries); cicatricial psoriatic alopecia (with erythema associated with yellowish, silver-white scales with twisted and bushy red loops capillaries) and pustular psoriasis (with 'flower shape' pustular lesions, erythema simple red loops capillaries). CONCLUSIONS: The description of different clinical patterns of scalp psoriasis and its trichoscopical correlations may help the clinician to make the diagnosis also in atypical presentations and to prescribe an adequate therapeutic regimen.

Demographic, clinical and dermoscopic features of melanocytic nevi on the scalp.

BACKGROUND: The scalp is a special anatomical area and dermoscopic findings of this region may significantly differ from other body parts. OBJECTIVE: To investigate and compare the clinical and dermoscopic patterns of scalp melanocytic nevi in patients ≤15 years of age and above, and to analyse their relevance to demographic features, atypical mole syndrome (AMS) and total body nevus count (TBNC). METHODS: In this retrospective cohort study, the clinical data and dermoscopic images of patients with scalp melanocytic nevi were retrieved, reviewed and analysed. Demographic, clinical and dermoscopic features were compared in patients ≤15 years of age and above. RESULTS: A total of 196 scalp melanocytic nevi in 126 patients (female/male:64/62; ≤15/>15 years of age: 49/77) with a median age of 18.5 years (range 0-72) were evaluated. Statistically, the globular pattern was significantly higher in all age groups, and the papillomatous pattern was significantly lower in patients ≤15 years of age (P = 0.008 and P = 0.005, respectively). The eclipse pattern was significantly higher, and the homogenous pattern was significantly lower in patients ≤15 years of age with AMS (P = 0.003 and P = 0.014, respectively). Finally, patients ≤15 years of age with 50 to 100 TBNC had a higher eclipse pattern than those with 0 to 25 TBNC. CONCLUSION: The findings of this retrospective study might implicate that children with eclipse pattern of scalp melanocytic nevi might be 'moley' in the future with an impending risk of AMS. This hypothesis requires confirmation in future prospective studies on a larger cohort of patients.