Patterns of Clinical Management of Atopic Dermatitis: A Survey of Three Physician Specialties in the Middle East.

INTRODUCTION: Atopic dermatitis (AD) is a complex inflammatory disease of the skin that has a significant impact on the well-being of patients and their families. The prevalence of AD has increased in developing countries and regions, including the Middle East. Despite similarities in the presentation of the disease, there is a lack of consistent management and treatment guidelines for AD. The objective of this survey was to develop further insight into the management patterns of AD from dermatologists, pediatricians, and primary care/family medicine physicians in the Middle Eastern nations of Egypt, Lebanon, the United Arab Emirates, and Saudi Arabia. METHODS: The survey was composed of 47 closed-ended, multiple-choice questions. These questions assessed physician and patient characteristics and treatment familiarity and approach. RESULTS: A total of 400 physicians, including 200 dermatologists, 100 pediatricians, and 100 primary care physicians, participated in the survey. The findings provide insight into the management of AD by physician specialty within the region. A diverse array of management approaches was observed for both referral patterns and treatments for AD in the Middle East. CONCLUSION: The diversity of management tactics highlights the lack of a standard approach for the management of AD throughout the Middle East.

Case Report: Bi-allelic missense variant in the desmocollin 3 gene causes hypotrichosis and recurrent skin vesicles.

Background: Hypotrichosis with Recurrent Skin Vesicles (HYPTSV) is an extremely rare condition, having autosomal recessive inheritance. Here in we report a 4-years- old Saudi boy who presented with a history of recurrent skin blisters that are localized to the extremities and hypotrichosis since birth. Methods: The present study describes a consanguineous Saudi family segregating HYPTSV in an autosomal recessive fashion. A single proband (II-1) exhibited features such as diffused non-scarring alopecia on the scalp, intraepidermal blister, post-inflammatory hyperpigmented macules, and follicular hyperkeratosis. DNA of the index was subjected to whole-genome sequencing (WGS). Furthermore, 3D protein modeling was performed for the mutated and normal protein. Results: WGS revealed a novel bi-allelic missense variant (c.154G>C; p. Val52Leu) in the DSC3 gene, which segregated perfectly using Sanger sequencing. In addition, 3D protein modeling revealed a substantial change in the mutated DSC3 protein as compared to the normal DSC3 protein. Conclusion: This is the 3rd novel variant reported in the DSC3 gene associated with the HYPTSV phenotype. This report further strengthens the evidence that bi-allelic variants in the DSC3 cause severe HYPTSV in humans.

Ichthyosis Prematurity Syndrome: A Rare Form but Easily Recognizable Ichthyosis.

Ichthyosis prematurity syndrome is a rare autosomal recessive genodermatosis that is associated with mutations in the SLC27A4 gene. Its onset occurs in early childhood and presents with the clinical triad of premature birth, thick caseous desquamating epidermis, and neonatal asphyxia. Here, we describe a prematurely born baby patient (33 weeks of gestation) with a homozygous variant at the initiation codon site (c.1 A> G, p.Met1Val) in the SLC27A4 gene to raise awareness of this rare syndrome despite its distinctive features as we believe it is still underdiagnosed.

Scalp roof tiles.: A new diagnostic sign in neonates with Netherton Syndrome.

CLINICAL PRESENTATION: A 2-month-old baby boy, of full-term spontaneous vaginal delivery, presented to the dermatology outpatient clinic with generalized erythroderma, which had been noted since birth. Family history was positive for similar disease in his eldest sister, who died at 6 months of age without a diagnosis. On examination, the patient looked ill with generalized erythroderma, yet there were no signs of ectropion, eclabium, or deformed ears. Diffuse scalp scaling was observed with interlocking tessellation scales over the scalp (Figure 1). Hair microscopy showed in Figure 2. All laboratory results were normal.

Genetic Profile of Epidermolysis Bullosa Cases in King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Epidermolysis bullosa (EB) is a rare heterogeneous genetic mechanobullous skin disorder that is characterized by increased skin fragility leading to blistering following minor trauma. EB may be inherited as an autosomal dominant or an autosomal recessive disorder and can be classified into dystrophic EB (DEB), junctional EB (JEB), and EB simplex (EBS). A total of 28 Saudi patients with EB were included in this observational, retrospective chart-review study. A consecutive non-probability sampling technique was used to approach all affected patients. Molecular analysis was done to test the patients' genomic DNA using a custom-designed AmpliSeq panel of suspected genes. All disease-causing variants were checked against available public databases. Twelve patients (42.9%) were found to have DEB, 6 patients (21.4%) with JEB, and 10 patients (35.7%) with EBS. The molecular genetic results revealed detections of 24 various homozygous genetic variations in the genes associated with EB, of which 14 were novel mutations. The most frequent variations were detected in COL7A1 in 12 cases (42.9%), followed by LAMB3 in 5 cases (17.9%), TGM5 in 4 cases (14.3%), and other genes. Furthermore, the majority (87.5%) of EB cases were confirmed to have homozygous mutations, and few were documented with positive consanguinity history. Only 3 cases (12.5%) were found to be autosomal dominant displaying heterozygous mutations. This is the first study to establish the EB genetic profile in Saudi Arabia where DEB is the most frequent type. A total of 14 novel mutations were identified that had not been previously reported. Consanguineous marriage is clearly recognized in the Saudi population; therefore, we propose a nationwide EB program that would help extend the spectrum of the genetic profile and help in the diagnosis and better understanding of this disease.

Report of a Case that Expands the Phenotype of Infantile Krabbe Disease.

BACKGROUND Krabbe disease, or globoid cell leukodystrophy, is an autosomal recessive disease caused by the deficiency of lysosomal galactocerebrosidase. The most common form is infantile Krabbe disease, which is usually diagnosed within the first year of life and has high morbidity and mortality. Patients usually present with irritability, progressive neurodegeneration, spasticity, and peripheral neuropathy. This report is of a 6-year-old girl who had Krabbe disease since she was 5 weeks of age. CASE REPORT A 6-year-old female Saudi patient had initially presented at 5 weeks of age with hypoventilation, recurrent attacks of fever, and failure to thrive. The patient also skin hypopigmentation involving the face, neck, upper extremities, and lower extremities. Peripheral blood galactocerebrosidase enzyme activity was normal but was reduced in tissue fibroblasts. Whole exome sequencing (WES) and whole genome sequencing (WGS) showed a homozygous mutation in the GALC gene c.334A>G (p.Thr112Ala), which was previously reported in a compound heterozygous state with another mutation. CONCLUSIONS This case report describes a patient with homozygous mutation status Krabbe disease. Although this patient had the phenotype of early infantile-onset Krabbe disease, which usually has high morbidity and mortality, her condition is now relatively stable at 6 years of age, which could be due to relatively higher enzyme activity. This case also expanded the presentation or typical phenotype of infantile Krabbe disease as the patient also presented with hypoventilation and skin hypopigmentation.

Multifocal congenital pyogenic granuloma successfully treated with oral propranolol.

Disseminated congenital pyogenic granuloma (DCPG) is an uncommon condition. Individual lesions of DCPG share clinical and histologic similarities with infantile hemangioma (IH); endothelial glucose transporter 1 (GLUT-1), which is highly expressed in IH but generally not in pyogenic granulomas (PG), is an important diagnostic tool. Treatment for DCPG remains difficult. We describe a case of DCPG effectively treated with propranolol.

Methionine adenosyltransferase I/III deficiency: beyond the central nervous system manifestations.

Methionine adenosyltransferase (MAT) I/III deficiency (OMIM # 250850) is caused by a mutation in MAT1A, which encodes the two hepatic MAT isozymes I and III. With the implementation of newborn screening program to discover hypermethioninemia due to cystathionine beta-synthase deficiency, more cases are being discovered. While the majority of patients are asymptomatic, some might have central nervous system (CNS) and extra-CNS manifestations. Although neurologic manifestations and demyelination have been correlated to MAT deficiency in many reported cases, none of the previous reports focused on extra-CNS manifestations associated with the disease. This is a retrospective chart review for a 40-month-old patient with confirmed diagnosis of MAT deficiency. He was found to have a novel homozygous disease-causing variant in MAT1A (NM_000429.2) c.1081G>T (p.Val361Phe). Interestingly, our patient had an unexplained zinc and iron deficiency in addition to mild speech delay. We reviewed the literature and summarized all the reported extra-CNS manifestations. In conclusion, MAT deficiency patients should be thoroughly investigated to check for CNS and extra-CNS manifestations associated with the disease. Keeping in consideration the challenge of assuming correlation, a scrutinized look at extra-CNS manifestations and their course with time might pave the way to understanding the pathophysiology of the disease and MAT1A function.

Peeling skin syndrome associated with novel variant in FLG2 gene.

Peeling skin syndrome is a rare genodermatosis characterized by variably pruritic superficial generalized peeling of the skin with several genes involved until now little is known about the association between FLG2 and peeling skin syndrome. We describe multiple family members from a consanguineous Saudi family with peeling skin syndrome. Next Generation Sequencing identifies a cosegregating novel variant in FLG2 c.632C>G (p.Ser211*) as a likely etiology in this family. Here, we reported on the clinical manifestation of homozygous loss of function variant in FLG2 as a disease-causing gene for peeling skin syndrome and expand the dermatology findings.

Cowden syndrome. Early presentation, late diagnosis.

Cowden syndrome is a rare genodermatosis characterized by the formation of hamartomas in various organs and increased risk of malignancy. This disease has variable expression and often presents with subtle skin signs, which can be missed. We report a 39-year-old Saudi male who presented with acral keratoses of Cowden syndrome, and misdiagnosed and treated by many dermatologists as viral wart. We aim to increase awareness of Cowden syndrome among health care workers.

Permanent alopecia following cranial irradiation in a child.

BACKGROUND: Cranial irradiation is commonly used in childhood leukemia, with many potential cutaneous adverse effects. Radiation-induced permanent alopecia owing to scalp fibrosis is a rare but disturbing side effect. OBJECTIVE AND CONCLUSION: Here we report a Saudi boy with acute T-cell lymphoblastic leukemia who developed radiation-induced cicatricial alopecia. Topical treatment using minoxidil solution was tried but was ineffective.

Fish tank granuloma: misdiagnosed as cutaneous leishmaniasis.

Mycobacterium marinum is an atypical mycobacterium that causes a skin infection known as fish tank granuloma or swimming pool granuloma affecting people who are exposed to aquatic environments. In general, it is managed medically with antimicrobials and variable treatment protocols. Here, we report a Saudi gentleman who acquired this infection in Thailand and was misdiagnosed as cutaneous leishmaniasis. After establishing the correct diagnosis, treatment with minocycline and trimethoprim-sulfamethoxazole resulted in rapid healing.

Practical tip: Precooling topical calcineurin inhibitors tube; reduces burning sensation.

Burning sensation at the site of application is the most common side effect of topical calcineurin inhibitors and is considered the most common reasons for premature discontinuation. Here, we analyze the possible mechanism(s) and offer a simple practical tip to mitigate this adverse effect. Simple cooling of the tube, immediately before use, does reduce the burning sensation and enable most intolerant patients to use the medication comfortably. We also discuss the possible explanation(s) for the success of this maneuver.