Extracutaneous Features Research Articles

PA15 Becker naevus syndrome associated with a mosaic pathogenic variant in ACTB

Abstract A 15-year-old girl presented with an 8-year history of a gradually enlarging, irregular, nonconfluent hyperpigmented patch on her left flank. The lesion demonstrated an area of increased hair growth, did not cross the midline and was mildly pruritic but otherwise asymptomatic. Another pigmented patch, present since birth, was also noted on her right lower back and was consistent with a café-au-lait macule. Medical history included a marfanoid phenotype with musculoskeletal complications including scoliosis and joint hypermobility, for which she was under the care of the orthopaedic team for bilateral patellar instability associated with recurrent dislocation. She was also noted to have increased skin laxity, mild pectus excavatum, mitral valve prolapse and symptomatic tachyarrhythmias. She was born at term, to nonconsanguineous parents, with no postnatal developmental concerns. There was a family history of an older brother with significant scoliosis and hip dysplasia requiring hip replacements, developing from the age of 14 years. Genetic testing was negative for FBN1 and five other genes associated with Marfan syndrome. Thyroid function and bone profile were normal. Menarche occurred at 11 years of age, and a full hormone profile was normal except for a mildly raised prolactin level, deemed to be a normal variant in puberty. Abdominal and pelvic ultrasounds were normal. Skin biopsy from the left flank revealed orthokeratosis, irregular elongation of rete ridges and sparse perivascular chronic inflammation in the superficial dermis. Next-generation sequencing and droplet digital polymerase chain reaction from DNA extracted from skin revealed de novo mosaic pathogenic variants in ACTB, which encodes β-actin, an intracellular protein involved in cell migration, signalling and proliferation. Recurrent mosaic variants in ACTB have previously been associated with 61% of Becker naevi and one case of Becker naevus syndrome in one study (Cai ED, Sun BK, Chian A et al. Postzygotic mutations in beta-actin are associated with Becker’s nevus and Becker’s Nevus syndrome. J Invest Dermatol 2017; 137:1795–8), as well as congenital smooth muscle hamartomas and odontomaxillary dysplasia. Our patient had cutaneous and extracutaneous features suggestive of Becker naevus syndrome. This rare syndrome predominantly involves skeletal and soft tissue abnormalities, with breast hypoplasia most frequently reported. Notable features here include a café-au-lait macule, scoliosis and pectus excavatum. This case highlights the value of DNA analysis from skin in confirming a diagnosis, after 9 years of presentation to paediatric services. Given the heterogeneous extracutaneous phenotypes, there are also important implications for counselling and screening of associated conditions.

Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache.

Sturge-Weber syndrome (SWS) is a congenital, sporadic, and rare neurocutaneous disorder, characterized by the presence of a facial port-wine birthmark (PWB), glaucoma, and neurological manifestations including leptomeningeal angiomatosis and seizures. It is caused by a postzygotic, somatic, gain-of-function variant of the GNAQ gene, and more recently, the GNA11 gene in association with distinctive clinical features. Neuroimaging can help identify and stratify patients at risk for significant complications allowing closer follow-up; although no presymptomatic treatment has been demonstrated to be effective to date, these patients could benefit from early treatment and/or supportive interventions. Choroid plexus (CP) thickness measurements in brain magnetic resonance imaging (MRI) have a high sensitivity and specificity for early and incipient changes in SWS. In contrast, the absence of pathologic findings makes it possible to rule out associated neurological involvement and leads to periodical observation, with new imaging studies only in cases of new clinical signs/symptoms. Periodic ophthalmological examination is also recommended every 3 months during the first year and yearly afterwards to monitor for glaucoma and choroidal hemangiomas. Treatment for SWS depends on the extent and areas that are affected. These include laser surgery for PWB, anticonvulsants in the case of brain involvement, with either seizures or abnormal EEG, and medical treatment or surgery for glaucoma. Sirolimus has been used in a limited number of patients and appears to be a safe and potentially effective treatment for cutaneous and extra-cutaneous features, however controlled clinical studies have not been carried out. Better knowledge of GNAQ/GNA11 molecular pathways will help to develop future targeted treatments.

Skin manifestations and clinical features of drug reaction with eosinophilia and systemic symptoms: a retrospective multicentre study of 125 patients.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated. This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features. We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews. Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P < 0.01). Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.

Bilateral nevus of Ota with palatal involvement, unilateral nevus of Ito, and a port-wine stain: A rare presentation

Nevus of Ota and nevus of Ito are dermal melanocytoses, usually presenting themselves as a bluish-black or grayish-brown, patchy, diffuse, or mottled pigmentation of the skin. They share a common pathogenic mechanism involving failure in the migration of melanocytes from the dermis to the epidermis and differ only in the sites of their distribution on the body. Nevus of Ota, often unilateral, may rarely be bilateral or may involve the oral mucosa. Even rarer is its association with nevus of Ito and other extracutaneous features. A port-wine stain is a form of congenital capillary malformation presenting itself as a pinkish-red to purple discoloration, most commonly of the unilateral head and neck area. Only 25% of cases occur on other sites of the body. The presence of a port-wine stain in conjunction with two different dermal nevi has been an exceedingly rarely reported entity. Herein, we report a 26-year-old male who presented himself with a bilateral nevus of Ota with oral mucosal involvement and associated with nevus of Ito and a port-wine stain.

Phacomatosis pigmentokeratotica.

A 20 yr old female† presented to the department of Dermatology and Sexually Transmitted Diseases, Safdarjung Hospital, New Delhi, India, in February 2019, with progressive asymptomatic brownish-black lesions on the face, neck and chest since birth. Examination revealed yellowish-brown verrucous papules and plaques arranged linearly along the lines of Blaschko on the forehead, nose, right pre-auricular area, neck and chest, suggestive of naevus sebaceous (Fig. 1A and B). Light brown-coloured patch of size 10 × 7 cm with overlying dark brown-to-black macules and papules, suggestive of speckled lentiginous naevus, was present on the left side of the face, extending from forehead to mandibular region (Fig. 2). Biochemical, ophthalmic, neurological and skeletal evaluation revealed no abnormality. Histopathological examination from verrucous plaque showed hyperkeratosis, acanthosis, papillomatosis and follicular plugging in the epidermis. Dermis showed increased number of enlarged sebaceous glands placed abnormally higher, with a few immature hair structures and dilated apocrine glands (Fig. 3). These features were consistent with naevus sebaceous.Fig. 1: (A) Yellowish-brown verrucous papules and plaques arranged linearly along lines of Blaschko, suggestive of naevus sebaceous. (B) Naevus sebaceous over the right pre-auricular area (inset showing similar lesion over anterior chest).Fig. 2: Light brown-coloured patch of size 10 × 7 cm with overlying dark brown-to-black macules and papules, suggestive of speckled lentiginous naevus.Fig. 3: Hyperkeratotic, acanthotic and papillomatous epidermis with follicular plugging. There are an increased number of closely set large sebaceous glands (black arrow) that are placed abnormally higher in the dermis along with a few immature hair structures (yellow arrow). Lower dermis shows dilated apocrine glands (blue arrow) (Hematoxylin and eosin, x100).Phacomatosis pigmentokeratotica (PPK) is a rare form of epidermal naevus syndrome characterized by coexistence of an organoid naevus with sebaceous differentiation along Blaschko’s lines and speckled lentiginous naevus in a checkerboard pattern. Our case represents a rare form of PPK without any extra-cutaneous features. Patients with PPK are at risk of developing basal cell carcinoma and syringocystadenoma papilliferum in naevus sebaceous and malignant melanoma in speckled lentiginous naevus; hence, regular follow up is necessary. The patient was planned for serial surgical excision of naevus sebaceous. Acknowledgment: Authors acknowledge Dr Shruti Sharma, Scientist D, National Institute of Pathology, Indian Council of Medical Research, New Delhi, for providing histopathologic image. Conflicts of Interest: None.

Clinical and dermoscopic analysis of generalised linear and whorled hypermelanosis in a child: A case report

Linear and whorled nevoid hypermelanosis (LWNH) is a rare sporadic disorder of pigmentation characterised by swirls and streaks of macular pigmentation along the lines of Blaschko. It can be frequently associated with extracutaneous features. We report clinical and dermoscopic presentation of a case of generalised linear and whorled nevoid hypermelanosis in a 1-year-old child involving the trunk and extremities while sparing the face, palms, soles and mucosae without any extracutaneous features.

Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis.

Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G>A, p.(Gly448Arg) and NM_014908.3: c.1558A>G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.

Management of pediatric generalized pustular psoriasis using biologics: An evidence-based review

Management of pediatric generalized pustular psoriasis using biologics: An evidence-based review

P04 Primary mediastinal large B-cell lymphoma in a Caucasian female with anti-SAE-1 positive dermatomyositis

Abstract Case report - Introduction This is a case of a female patient who was diagnosed with dermatomyositis with anti-Small ubiquitin-like modifier Activating Enzyme-1 (SAE-1) and anti-Ro52 autoantibodies. She had extensive skin involvement with mild extracutaneous features and responded well to a combination of prednisolone, hydroxychloroquine and azathioprine. She subsequently developed primary mediastinal large B-cell lymphoma about 3 years after diagnosis of dermatomyositis. Case report - Case description A 59-year-old Caucasian female presented in January 2018 to the dermatologist with a 6-month history of itchy, dry, flaky skin around her eyes with periorbital erythema which later progressed to fixed periorbital oedema. At that point, a diagnostic biopsy was taken from the left lower eyelid which showed a deep inflammatory infiltrate with significant oedema and dilated blood vessels. A few weeks later, she developed a widespread erythematous rash. Other than some cramps and myalgia in the thighs, there was no muscle weakness or dysphagia. There were no red flag symptoms, but some dry cough without dyspnoea. Clinical examination revealed periungual erythema, periorbital erythema and oedema, widespread erythematous eruption on the torso and limbs and papular eruptions on the hand dorsum. Muscle power in upper and lower limbs scored 5 in the MRC scale. Blood tests showed slight lymphopaenia, antinuclear antibodies titre 1:400, dsDNA and ENA negative, raised IgG kappa monoclonal protein at 10g/L with normal kappa/lambda ratio, creatine kinase initially 93 that later rose to 209, slightly raised lactate dehydrogenase 262, otherwise unremarkable biochemistry and inflammatory markers. Extended myositis screen with immunoblot revealed positive SAE-1 and anti-Ro52 autoantibodies. MRI of the femurs showed mild oedema in the adductors. Electromyogram showed some myopathic motor units, not florid but convincingly present. Computed tomography of neck, thorax, abdomen and pelvis did not reveal any underlying malignancy at the time. The diagnosis of SAE-1-positive dermatomyositis was made and she was treated with high-dose prednisolone (1mg/kg), azathioprine and hydroxychloroquine with good response and dermatomyositis went into remission. In December 2020, she developed dyspnoea and was found to have left-sided pleural effusion and anterior mediastinal mass, a biopsy of which confirmed primary mediastinal large B-cell lymphoma. She is currently receiving chemotherapy with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone and azathioprine was discontinued. Her dermatomyositis remains in remission. Case report - Discussion The SAE-1 autoantibody was first identified in 2007. Its prevalence ranges from 1% to 8% in different cohorts. The main clinical feature of anti-SAE-1-positive disease tends to be a widespread cutaneous involvement which is typically pruritic, either amyopathic or associated with mild muscle involvement. Other extracutaneous manifestations include arthralgia, dysphagia and interstitial lung disease (ILD) with variable frequency in different cohorts. ILD is usually milder than in other amyopathic dermatomyositis subgroups. Our patient presented with rather extensive cutaneous disease (clinical photography available) requiring high-dose prednisolone and we decided to add azathioprine as a steroid-sparing agent. She had minimal muscle disease and no other extracutaneous manifestations. Interestingly, she developed lymphoma 3 years following the diagnosis of dermatomyositis. The association between dermatomyositis and malignancy is well-established. The generally accepted definition of cancer-associated myositis is malignancy within 3 years of disease onset. Dermatomyositis as opposed to polymyositis, increasing age, male sex, dysphagia, cutaneous ulceration and the presence of anti-transcription intermediary factor-1 gamma antibodies (TIF1γ) were all associated with increased cancer risk in a recent meta-analysis by Oldroyd et al. Anti-SAE-1 is variably reported to be associated with cancers. A recently published study of a North American cohort of anti-SAE-1-positive dermatomyositis patients reported five cases of cancers, mainly internal malignancies and one case of B-cell lymphoproliferative disorder. We are not aware of any more reported cases of lymphoma in patients with anti-SAE-1 autoantibodies. A 2018 study did report two cases of dermatomyositis patients who developed lymphoma without specifying the autoantibody profile in those patients. Our case contributes to the fact that dermatomyositis can be associated with malignancies. It also raises awareness that this rare subgroup of dermatomyositis with SAE-1 autoantibodies can be associated with lymphoma. However, this association has not been widely reported in the literature. Case report - Key learning points

Leprosy suspect presenting at a chest clinic.

Leprosy is an ancient ailment, also known as Hansen's disease. It primarily involves the superficial peripheral nerves, skin, upper respiratory tract mucosa, eyes, bones and testicles, but not the lungs. Although leprosy patients are not included in the study area of pulmonology, here we present an undiagnosed leprosy patient with a history of smoking, who was referred owing to upper respiratory tract symptoms and bilateral pleural effusions. From this undiagnosed case, we would like to draw specific attention of pulmonologists, since a patient with leprosy can present in this way due to hypoalbuminemia resulting from a systemic inflammatory state, which may then progress to sepsis. Collaboration of different specialists may be required to clinch extra-neurological and extra-cutaneous features of leprosy.

Importance of extracutaneous organ involvement in determining the clinical severity and prognosis of incontinentia pigmenti caused by mutations in the IKBKG gene.

Incontinentia pigmenti (IP) is a rare X-linked skin disease caused by mutations in the IKBKG gene, which is required for activation of the nuclear factor-kappa B signalling pathway. Multiple systems can be affected with highly variable phenotypic expressivity. We aimed to clarify the clinical characteristics observed in molecularly confirmed Korean IP patients. The medical records of 25 females confirmed as IP by molecular genetic analysis were retrospectively reviewed. The phenotypic score of extracutaneous manifestations was calculated to assess the disease severity. The IKBKG gene partial deletion or intragenic mutations were investigated using long-range PCR, multiplex ligation-dependent probe amplification and direct sequencing methods. Among the 25 individuals, 18 (72%) were sporadic cases. All patients showed typical skin manifestations at birth or during the neonatal period. Extracutaneous findings were noted in 17 (68%) patients; ocular manifestations (28%), neurological abnormalities (28%), hair abnormalities (20%), dental anomalies (12%), nail dystrophy (8%). The common exon 4-10 IKBKG deletion was observed in 20 (80%) patients. In addition, five intragenic sequence variants were identified, including three novel variants. The phenotype scores were highly variable, ranging from abnormal skin pigmentation only to one or more extracutaneous features, although no significant difference was observed for each clinical characteristic between the group with sequence variants and that with common large deletion. Our cohort with IP showed heterogeneity of extracutaneous manifestations and high incidence of sporadic cases. Long-term monitoring with multidisciplinary management is essential for evaluating the clinical status, providing adequate genetic counselling and understanding the genotype-phenotype correlation in IP.

O22 An inflammatory journey from brain to skin: a case of En Coupe De Sabre scleroderma presenting with raised intracranial pressure, seizures, and uveitis

O22 An inflammatory journey from brain to skin: a case of En Coupe De Sabre scleroderma presenting with raised intracranial pressure, seizures, and uveitis

Epidermolysis bullosa with congenital absence of skin: Review of the literature

Bart syndrome was initially described as association of congenital absence of skin (CAS), nail abnormalities, and epidermolysis bullosa (EB). Further reports of patients with CAS and EB have been made with wide clinical heterogeneity among them. Current guidelines recommend the elimination of eponyms and use of the descriptive term EB with CAS. We performed a PubMed and Medline database search of patients with Bart syndrome or EB with CAS. We included case reports or case series that contained clinical and demographic information. After review, 55 articles were included, reporting 96 patients. CAS involved the lower extremities in all patients, with additional upper limb, trunk, or head involvement in 17%. In all patients, the time to healing ranged from 2weeks to 6months; most received only conservative treatment. The subtype and frequency of associated EB most frequently reported were recessive dystrophic EB (41.4%) and dominant dystrophic EB (22.8%). Extracutaneous features were present in 29 patients; with pyloric atresia and ear malformations being the most common. The prognosis varied based on the subtype of EB and the presence of additional comorbidities; 50% of the patients with junctional EB with pyloric atresia and CAS died during the first months of life, while mortality among those with recessive dystrophic EB was 6.8%. Epidermolysis bullosa with CAS is a clinically heterogeneous disorder, most often associated with recessive dystrophic EB, but other EB subtypes may occur. Further investigations are necessary to better establish a pathological mechanism for CAS, and its association with EB.

Comparing paediatric- and adult-onset linear morphoea in a large tertiary-referral scleroderma centre.

Linear morphoea is a severe morphoea subtype associated with extracutaneous manifestations, potentially permanent disfigurement and functional impairment. Linear morphoea is more prevalent in paediatric patients, and knowledge of disease in adults is limited. The objective of this study was to compare paediatric- and adult-onset linear morphoea, in an exclusively adult population. This was a retrospective cohort study of adult patients with linear morphoea seen over a 3-year period at a single-site adult tertiary-referral Connective Tissue Disease centre. Clinical markers of disease severity and course, including anatomical distribution, extracutaneous manifestations, cutaneous symptoms, associated autoimmunity, inflammatory blood parameters, Dermatology Life Quality Index scores, treatment requirements and modified Localised Scleroderma Activity Tool were assessed and compared in paediatric- and adult-onset linear morphoea. Of 298 patients with morphoea seen during the study period, 135 had linear morphoea and 133 were included in the study. Most were female (78.9%), the mean age was 36.5 years and almost half (43.6%) had adult-onset disease. Disease was similarly severe between groups with regard to anatomical distribution, cutaneous symptoms (n = 89, 66.9%), extracutaneous manifestations (n = 76, 57.1%), antinuclear antibody-positivity (n = 40, 40.4%), raised erythrocyte sedimentation rate (n = 27, 25.0%) and associated autoimmune diagnoses (n = 15, 11.3%). Prescribed treatments were similar between groups; 73.7% receiving methotrexate and almost one-third (32.3%) requiring more than one steroid-sparing agent. Those with paediatric-onset had more disease-related damage, with a mean modified Localised Scleroderma Skin Damage Index score of 19.5 (95% confidence interval: 17.0-22.0) versus 8.1 (95% confidence interval: 4.4-11.8; p < 0.001). Significantly more patients with adult-onset linear morphoea had quiescent disease (p = 0.0332), and even after correcting for disease duration, paediatric-onset patients still had 2.6 times greater odds of active disease (odds ratio = 2.59, 95% confidence interval: 0.9-7.6; p = 0.083). Linear morphoea in adults can be a severe disease with extracutaneous, autoimmune and systemic features. Adults with paediatric-onset disease appear to have more severe cumulative damage, greater functional impairment and ongoing disease activity. This patient subgroup may require particularly close monitoring and more aggressive therapy.

A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients

BackgroundX-linked ichthyosis (XLI; OMIM# 308100) is a recessive keratinization disorder characterized by the presence of dark brown, polygonal, adherent scales on different parts of the body surface. It almost exclusively affects males and the estimated prevalence ranges from 1:2000–6000 in males worldwide. Extracutaneous manifestations are frequent including corneal opacities, cryptorchidism, neuropsychiatric symptoms or others. Up to 90% of XLI cases are caused by recurrent hemizygous microdeletion encompassing entire STS gene on chromosome Xp22.3, while only a minority of patients shows partial deletions or loss of function point mutations in STS. Larger deletions also involving contiguous genes are identified in syndromic patients.MethodsHere, we report clinical and genetic findings of a large Pakistani family having 16 affected individuals including 2 females with XLI. Molecular karyotyping and direct DNA sequencing of coding region of the STS gene was performed.ResultsThe clinical manifestations in affected individuals involved generalized dryness and scaling of the skin with polygonal, dark scales of the skin on scalp, trunk, limbs, and neck while sparing face, palms and soles. There were no associated extra-cutaneous features such as short stature, cryptorchidism, photophobia, corneal opacities, male baldness, and behavioral, cognitive, or neurological phenotypes including intellectual disability, autism or attention deficit hyperactivity disorder. Molecular karyotyping was normal and no copy number variation was found. Sanger sequencing identified a novel hemizygous nonsense mutation (c.287G > A; p.W96*), in exon 4 of STS gene in all affected male individuals. In addition, two XLI affected females in the family were found to be homozygous for the identified variant.ConclusionsThis study is useful for understanding the genetic basis of XLI in the patients studied, for extending the known mutational spectrum of STS, diagnosis of female carriers and for further application of mutation screening in the genetic counseling of this family.

Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases.

Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders. To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism. This was a consensus expert review as part of the European Reference Network project (ERN-Skin). This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism. What's already known about this topic? Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes. Some cutaneous patterns are known to be seen in mosaicism. Very few treatment options are available for most mosaic abnormalities of the skin. Recent high-sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature. What does this study add? Expert consensus from the European Reference Network project. Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype. Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential. Practical tips on correct sample collection and genetic investigation. Review of trials of targeted therapies. Guidelines for a practical clinical approach to the patient with suspected mosaicism.

Italian translation, cultural adaptation, and pilot testing of a questionnaire to assess family burden in inherited ichthyoses

BackgroundInherited ichthyoses are rare disorders characterized by generalized skin scaling. Among them, autosomal recessive congenital ichthyoses (ARCI) form a major subgroup presenting lifelong and severely disabling cutaneous and extracutaneous features and symptoms for which no curative treatment is available. Management relies on daily time-consuming and distressing topical medications. Disease manifestations, symptoms, and daily care affect not only the patient self-perception, but also different dimensions of patient and family life. To date, there is only a French validated ichthyosis-specific questionnaire, “Family Burden in Ichthyosis” (FBI), for the evaluation of family disease burden. It addresses economical aspects, daily life, familial and personal relationships, work, and psychological impact. The aim of our study was to develop an Italian translation of the French FBI questionnaire and to pilot-test it in ARCI patients.MethodsThe guidelines for cross-cultural adaptation of health-related quality of life measures were followed. Specifically, two independent forward translations were produced, followed by a reconciliation step by a multidisciplinary expert committee and back-translation. Revision of the original text and all translations was performed by the expert committee leading to a final version, which was pilot-tested by cognitive debriefing on 10 caregivers whose comments were evaluated by the committee.ResultsThe translation and reconciliation process led to minor changes in five items in order to clarify the questions in relation to the possible answers or to obtain semantic/idiomatic/cultural equivalence of the Italian version with the French one. The cognitive debriefing process resulted into further minor wording modifications in four items to describe more precisely the disease impact according to parents’ comments. The FBI developer approved the final Italian FBI version.ConclusionsThe Italian version of the FBI generated in the present study is a useful instrument to measure the impact of ichthyosis on family daily life, education and working activities, psychological implications, and the disease economic load. The questionnaire will be further validated through a multicenter Italian study on burden of ARCI. A validated Italian questionnaire is a valuable tool for future clinical trials. In addition, it can be used to rapidly identify family distressing situations, which require attention and prompt intervention.

Cutaneous Sarcoidosis- A not so Rare Entity in Pakistan

Objective: To study the demographic characteristics, clinicopathological features and radiological stage of cutaneous sarcoidosis in a public sector tertiary care hospital of the largest metropolitan city of Pakistan. Methods: A case series was conducted from August 2014 to July 2017 at the Dermatology department of Civil Hospital Karachi. Case records of cutaneous sarcoidosis patients with a histopathological diagnosis of noncaseating sarcoidal granuloma on skin biopsy were reviewed. Diagnosis was done based on clinical manifestations, radiologic examinations and pathologic data. Results: Mean age at the time of diagnosis was 35.8 years, while the mean duration of disease was 31.6 months. Plaques were found in five patients (50%), one of whom had coexistent plaques and nodules. Three patients (30%) displayed subcutaneous lesions, whereas two patients (20%) had maculopapules. Extracutaneous involvement occurred in six patients (60%), affecting mainly lungs and lymph nodes. Skin biopsy revealed typical sarcoid non-caseating granulomas in nine cases (90%). Radiological evaluation revealed Stage 0 in six patients (60%), Stage 1 and 3 in one patient (10%), while two patients (20%) showed Stage 2 involvement. The mainstay of treatment was topical or systemic corticosteroids to which a good response was achieved. Conclusion: Our study concurred with the literature in that sarcoid plaques are the most common lesions while the involvement of the lungs and lymph nodes are the commonest extracutaneous features. Moreover, since cutaneous sarcoidosis leads to a diverse range of presentation, diagnosis in countries like Pakistan, where tuberculosis is endemic can be overlooked. Therefore, further studies are needed to overcome this diagnostic dilemma.

Hereditary palmoplantar keratodermas. Part I. Non-syndromic palmoplantar keratodermas: classification, clinical and genetic features.

The term palmoplantar keratoderma (PPK) indicates any form of persistent thickening of the epidermis of palms and soles and includes genetic as well as acquired conditions. We review the nosology of hereditary PPKs that comprise an increasing number of entities with different prognoses, and a multitude of associated cutaneous and extracutaneous features. On the basis of the phenotypic consequences of the underlying genetic defect, hereditary PPKs may be divided into the following: (i) non-syndromic, isolated PPKs, which are characterized by a unique or predominant palmoplantar involvement; (ii) non-syndromic PPKs with additional distinctive cutaneous and adnexal manifestations, here named complex PPKs; (iii) syndromic PPKs, in which PPK is associated with specific extracutaneous manifestations. To date, the diagnosis of the different hereditary PPKs is based mainly on clinical history and features combined with histopathological findings. In recent years, the exponentially increasing use of next-generation sequencing technologies has led to the identification of several novel disease genes, and thus substantially contributed to elucidate the molecular basis of such a heterogeneous group of disorders. Here, we focus on hereditary non-syndromic isolated and complex PPKs. Syndromic PPKs are reviewed in the second part of this 2-part article, where other well-defined genetic diseases, which may present PPK among their phenotypic manifestations, are also listed and diagnostic and therapeutic approaches for PPKs are summarized.

Concomitant presence of bilateral nevus of Ota with unilateral nevus of Ito and halo nevus: a rare association

&lt;p&gt;Nevus of Ota is dermal melanocytosis, generally presents as blue-black or gray-brown patchy diffuse pigmentation. Most commonly occurs unilaterally on face in areas innervated by the first and second divisions of trigeminal nerves. Bilateral involvement and oral mucosal involvement can occur, but as a rare manifestation. Nevus of Ota may be very rarely associated with the nevus of Ito and other extra cutaneous features. The halo nevus may be seen in congenital or acquired melanocytic nevi. Presence of halo nevus in conjunction with two different dermal nevi is not reported till date. We are reporting 19 year old female presented with bilateral Nevus of Ota with oral mucosal involvement and associated nevus of Ito and halo nevus.&lt;/p&gt;