Extracutaneous Findings Research Articles

Gorlin Syndrome: A Comprehensive Evaluation of Skin Findings.

Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other. The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated. A total of 30 patients were diagnosed with Gorlin syndrome of whom 36.7% were children. BCC was the most common finding (90%) followed by OKCs (83.3%), skeletal system anomalies (76.7%), and palmoplantar pitting (76.7%). While classical BCC (63.3%) lesions were the predominant clinical subtype among all patients, acrochordon-like or small-sized papular BCCs were seen in 45.4% of pediatric patients. Three patients, 2 of whom were children, had BCC lesions in the palmoplantar region in association with palmoplantar pitting. Epidermoid cysts presenting clinically as solitary (n = 12) or a few nodules (n = 4) without punctum, located more commonly in acral areas (n = 10) were seen in 16 (53.3%) patients of whom 7 were children. Epidermoid cysts were seen in 60% of patients with OKCs, and the relationship between epidermoid cysts and OKCs was not statistically significant (P = .15). Extracutaneous tumors such as medulloblastoma (n = 3), cardiac fibroma (n = 1), and ameloblastoma (n = 1) were also recorded. The awareness of papular or acrochordon-like BCCs, palmoplantar BCCs, and acral epidermoid cysts without punctum may facilitate early diagnosis of Gorlin syndrome in children.

O08 Severely pruritic juvenile dermatomyositis

Abstract A 7-year-old female with type IV skin and autism spectrum disorder presented with a 4 month history of progressive proximal myopathy, weight loss and 20 month history of a worsening, intensely pruritic rash. Cutaneous examination showed a widespread eczematous eruption, post-inflammatory hypopigmentation, heliotrope rash and firm subcutaneous changes, in addition to palmar-plantar papules, pustules and burrows. Extra-cutaneous findings included multiple fixed flexion deformities and muscle wasting. Investigations revealed a normocytic anaemia, elevated muscle enzymes, strongly positive anti-nuclear antibodies and negative myositis-specific antibodies. Whole body MRI reported proximal muscle oedema. Skin biopsy demonstrated lichenoid and perifollicular inflammation, dermal mucin and subcutaneous calcification. Clinical findings were consistent with a diagnosis of juvenile dermatomyositis (JDM), complicated by concurrent scabies. Prednisolone in combination with methotrexate was commenced as first-line therapy in line with current consensus JDM treatment plans, in addition to topical steroids and sun protection. Muscle power started to improve after 5 months but ongoing cutaneous inflammation prompted second-line therapy with IV immunoglobulin. Oral ivermectin was required for the management of scabies due to topical permethrin failure. JDM is a rare autoimmune small-vessel vasculopathy with significant morbidity and limited evidence-based guidelines. Unlike adult-onset disease there is no racial predilection or association with malignancy. Calcinosis is more common in children but early treatment reduces disease complications. JDM has a variable disease course with a median time to remission of 4.67 years. Residual skin changes are increasingly recognised to be an early predictor of prolonged recovery time and these patients may benefit from biologic agents.

P16 Linear bullous aplasia cutis congenita of the scalp: an unusual presentation of a rare condition

Abstract Aplasia cutis congenita (ACC) is a heterogenous group of congenital disorders characterized by focal or widespread absence of skin. Bullous ACC is a rare variant that presents with well-circumscribed oval lesions resembling bullae or vesicles covered with a thin membrane. There have been 20 previously reported cases of bullous ACC. We present a female neonate referred to dermatology at day 2 of life following an IVF-assisted pregnancy and delivery by elective caesarean section for breech presentation. There was no antenatal history of infection, trauma or drugs, and no relevant family history. Clinical examination of the parietal scalp revealed five well-demarcated bullae in a linear distribution along Blaschko lines. The hair collar and ‘golf club set’ signs were absent. Skin swabs for microbiology and viral studies were negative. Ultrasonography showed no associated osseous defect. Clinical examination was otherwise normal. A diagnosis of multibullous ACC was made, and a conservative approach adopted. Clinical follow up at 2 years found resorption of one bulla with flattening of the remainder. Neurodevelopment was normal. On review of the literature, 10/20 (50%) cases of bullous ACC presented with multiple bullae. The hair collar sign was positive in 50%, strengthening theories that bullous ACC may represent a ‘forme fruste’ of a neural tube defect. Four other cases reported distribution along Blashko lines, suggesting possible underlying cutaneous mosaicism. The majority (90%) had no associated cutaneous or extracutaneous findings. Clinical outcomes were good with spontaneous resorption of bullae, suggesting conservative management is appropriate in most cases.

Feline sporotrichosis: Characterization of cutaneous and extracutaneous lesions using different diagnostic methods.

Sporotrichosis is a mycotic infection of the cutaneous and subcutaneous tissues caused by Sporothrix spp. that can also cause extracutaneous manifestations. This study aimed to characterize cutaneous and extracutaneous sporotrichosis lesions in cats. Over 1 year, 102 cats rescued by the Zoonoses Control Center of Belo Horizonte, Brazil, euthanized with clinical suspicion of feline sporotrichosis were evaluated. After euthanasia, the animals were evaluated by macroscopic, cytological, histopathological, and immunohistochemistry (IHC) examinations; fungal culture; and polymerase chain reaction (PCR). Sporothrix infection was identified by at least one diagnostic technique in all cats (n = 102) evaluated by postmortem examination, including 26/28 cases (93%) evaluated by IHC, 66/90 cases (73%) evaluated by cytology, 70/102 cases (68.6%) evaluated by histopathology, and 62/74 cases (84%) evaluated by fungal culture. Two cats had positive results only by fungal culture. Cytology and histopathology examinations were effective in diagnosing sporotrichosis, although IHC was needed to confirm the diagnosis in cats with low fungal loads. Sporothrix brasiliensis was confirmed by the sequencing of 3 samples. Skin lesions were characterized mainly by pyogranulomatous to granulomatous dermatitis (frequently with subcutaneous inflammation) with different intensities of Sporothrix spp. yeast. Extracutaneous findings associated with sporotrichosis included rhinitis or rhinosinusitis, lymphadenitis, pneumonia, meningitis, periorchitis, conjunctivitis, and glossitis. Extracutaneous infections were observed in 74/102 cases, and a possible association between the chronicity of the disease and the higher pathogenicity of this fungal species in cats requires further investigation.

Cutis marmorata telangiectatica congenita: Incidence of extracutaneous manifestations and a proposed clinical definition.

Cutis marmorata telangiectatica congenita (CMTC) is a capillary malformation characterized by congenital, reticulated, well-demarcated dark blue, red-purple, or violaceous macules or plaques, with a coarse fixed livedo pattern. Nearly always, contiguous areas of skin atrophy and/or ulceration are present. CMTC is usually localized but may rarely be generalized. Such generalized cases may be a feature of Adams-Oliver syndrome (AOS). The nosologic confusion surrounding the term CMTC and uncertainty about the risk of associated abnormalities hinders the appropriate workup of patients and prognostic counseling for families. We hypothesized that the risk of associated anomalies in children with localized CMTC is very low. We performed a literature review and retrospective review of patients with CMTC to propose a more precise clinical definition and ascertain the risk of associated anomalies. We included 78 patients determined to have a diagnosis of CMTC based on consensus. The majority of patients had localized CMTC. Most patients with generalized CMTC met the criteria for the diagnosis of AOS. The associations found in patients with localized CMTC were mostly dermatological, with atrophy, ulcerations, or erosions present in 71%. Extracutaneous findings were present in 34.4% of patients and consisted mainly of extremity asymmetry (24.5%) that improved over time. Our study showed a very low frequency of extracutaneous anomalies among patients with localized CTMC, ipsilateral limb discrepancy being the most common. We did not find a strong association with any other visceral anomalies that would justify routine evaluation in patients with localized CMTC.

A Case of Subcutaneous Sarcoidosis Treated With Intralesional Kenalog

Abstract Sarcoidosis is a granulomatous disorder that is characterized by the development of noncaseating granulomas affecting multiple organ systems, most commonly the lungs and lymph nodes of the body. Aside from these organ systems, sarcoidosis can also affect the skin, eyes, central nervous system, liver, heart, kidneys, and musculoskeletal system. We present a patient with subcutaneous sarcoidosis, also known as Darier-Roussy disease, without extracutaneous findings. Patients may benefit from topical or intralesional steroids for localized involvement to decrease the size of the nodules while avoiding the adverse effects of systemic medications.

899 Phenotypic and genomic characterization of eight patients with patterned cutaneous hypopigmentation associated with extracutaneous findings

899 Phenotypic and genomic characterization of eight patients with patterned cutaneous hypopigmentation associated with extracutaneous findings

Clinical characteristics of 47 children with pigmentary mosaicism: A cross-sectional study

BackgroundPigmentary mosaicism (PM), also known as Blaschkoid dyspigmentation, is a rare pigmentary anomaly. Although several case reports have been published describing extracutaneous manifestations associated with PM, there are very few studies on the clinical characteristics of patients with PM. AimTo describe the clinical characteristics of patients with PM. Patients and methodsThis descriptive cross-sectional study was conducted among 47 children examined by a dermatologist and a pediatrician. The pattern and location of the PM, type of pigmentation and extracutaneous manifestations were documented. ResultsThe most common pattern of PM was narrow-band PM, followed by broad-band and checkerboard patterns. The trunk was the most affected region, followed by the legs and arms. PM manifested as hypopigmentation in 51.1% of cases, as hyperpigmentation in 27.6%, and as hypo/hyperpigmentation in 21.2%. Accompanying diseases were present in 40.4% of patients: neuropsychiatric diseases were the most common, followed by endocrinological or hematological diseases and growth/developmental delay. ConclusionPM has been associated with several extracutaneous findings but there is still some debate whether these associations reflect different PM phenotypes or whether they are simply coincidental. Our study suggests that extracutaneous involvement in PM patients is frequent, thus warranting careful examination of PM patients.

Persistent Generalized Cutis Marmorata Telangiectatica Congenita with Venectasia.

Persistent Generalized Cutis Marmorata Telangiectatica Congenita with Venectasia.

292 Heterozygous pathogenic variants affecting the the highly conserved VWFA domain of integrin-β4 cause isolated nail dystrophy

Pathogenic variants in ITGB4 cause various forms of autosomal recessive epidermolysis bullosa (EB). ITGB4 encodes integrin-β4, which plays a critical role in the maintenance of the skin basement membrane integrity. Here, we aimed to delineate the genetic basis of dominant isolated nail dystrophy in 2 families. We studied a total of five affected individuals with nail dystrophy and no other cutaneous or extra-cutaneous findings. Whole exome sequencing revealed a different heterozygous missense variant in ITGB4 gene in each of the 2 families.

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

Acral lesions in a pediatric population during the COVID-19 pandemic: a case series of 36 patients from a single hospital in Spain

BackgroundTo describe the cutaneous acral findings in a pediatric population noticed during this pandemic.MethodsA retrospective descriptive study was performed collecting data on 36 patients under 14 years old, presenting suspicious acral skin manifestations for coronavirus disease 2019 (COVID-19).ResultsPatients were mostly male (63.8%). The mean age was 11.11 years. 66.67% of patients showed erythematous papules, and 44.44% purpuric macules. Feet were affected in 97.22% of patients and hands in 5.55%. Lesions were asymptomatic in 50% of patients. 30.55% of patients showed extracutaneous findings, preceding skin lesions in 12.62 days. Seven patients underwent specific severe acute coronavirus 2 (SARS-CoV-2) testing; all of these patients tested negative.ConclusionsThe association between these symptoms and SARS-CoV-2 remains unclear. We recommend using these manifestations as a sign of SARS-CoV-2 infection in children. This could lead to the examination of asymptomatic and mildly symptomatic children so that contagions may be avoided.

Erythema elevatum et diutinum as a systemic disease

Erythema elevatum et diutinum (EED) is a rare, chronic dermatosis. It has been associated with extracutaneous findings, including arthralgias, scleritis, panuveitis, peripheral ulcerative keratitis, oral and penile ulcers, and neuropathy. Additionally, EED is connected with various systemic diseases, including HIV, IgA paraproteinemia, myelomas, neutrophilic dermatoses, and inflammatory bowel diseases. The presence of such extracutaneous manifestations in EED patients suggests that EED may be a multiorgan entity. Extracutaneous manifestations in EED may involve deposition of circulating immune complexes; thus, patients with EED should be evaluated for systemic manifestations to ensure targeted management.

Patterned cutaneous hypopigmentation phenotype characterization: A retrospective study in 106 children.

Cutaneous patterned hypopigmentation's phenotype is highly variable and may be associated with extracutaneous anomalies. We evaluated the phenotypic and clinical characteristics of patients with cutaneous patterned hypopigmentation to determine whether certain patterns were more likely to be associated with underlying anomalies. The charts of 106 children with cutaneous patterned hypopigmentation were reviewed retrospectively (2007-2018) at Sainte-Justine University Hospital Centre, in Montreal, Canada. Retrieved information included sex, age at diagnosis, phototype, pattern, and distribution of the cutaneous lesions and the presence of extracutaneous findings. Data were recorded on a software tool which collects and analyzes phenotypic information. The predominant types of cutaneous patterned hypopigmentation were along Blaschko's lines in narrow (38.7%) and broad bands (53.8%). Mixed patterns were observed in 22.5% of children. The anterior trunk and posterior trunk were most frequently affected (69% and 56%, respectively). Extracutaneous involvement, especially neurological and developmental, was present in 28.3% of patients and was significantly associated with ≥4 involved body sites. Distribution and types of cutaneous patterned hypopigmentation were not predictive of extracutaneous findings, with the exception of multiple sites involvement and possibly centrofacial location and blocklike lesions. Follow-up until school entry should help identify subtler associated extracutaneous anomalies.

Angioma serpiginosum: a case report and review of the literature

BackgroundAngioma serpiginosum is a rare vascular anomaly whose pathogenesis is still unknown. It is characterized by the onset of vascular reddish macules and papules during childhood, lesions are usually monolateral with a linear serpiginous pattern. It is rarely associated with extracutaneous findings. This entity has not yet been included in the classification of the International Society for the Study of Vascular Anomalies.Case presentationWe describe the first Italian report of angioma serpiginosum with a congenital symmetrical presentation. The patient had a further extension of macules during puberty involving both of the soles. No extracutaneous manifestations were present. Diagnosis was confirmed with dermoscopy and light microscopy that revealed the typical clusters of dilated, thickened and PAS+ capillaries in the upper dermis. Moreover, Immunohistochemistry showed positive WT-1 staining. Genetic analysis with next generation sequencing did not detected any mutation.ConclusionsOur patient presented a peculiar symmetrical and planar extension with a serpiginous linear pattern. The proliferative nature of this condition has been widely discussed in literature. In our case immunohistochemistry was positive for Wilms tumor-1, a new endothelial marker expressed during angiogenesis in reparative processes and endothelial tumors.Clinical evolution, histological and immunohistochemical findings suggest that angioma serpiginosum should be considered as a vascular proliferation. For these reasons we think it should be included in the international classification as a tumor.

Newborn Girl with Rapidly Progressive Linearly Distributed Vesicles and Pustules

One-day old infant girl, born at term, presents with blanching erythematous macules, vesicles and pustules scattered on her upper and lower extremities. These lesions progressed rapidly and began to coalesce and take on a linear configuration, even appearing on her trunk and face. A punch biopsy revealed eosinophilic spongiosis. Based on skin findings and histopathology this girl was diagnosed with Incontinentia pigmenti (IP) in accordance with the IP Diagnostic Criteria 2013. IP is a rare, X linked dominant genetic syndrome occurring in 1 of 50,000 births. IP presents with characteristic cutaneous lesions and in varying frequency, extracutaneous manifestations. The cutaneous manifestations appear in four progressive stages. The first stage consists of multifocal and coalescing erythematous macules and patches with overlying tense vesicles on the patient’s trunk and extremities. These lesions are distributed along Blashko lines. In stage two, the lesions become hyperkeratotic appearing similar to viral warts. The lesions in the third stage darken and become hyperpigmented. They may appear as swirled macules. In the final stage hypopigmentation of the lesion occurs. Cutaneous symptoms often do not require additional medical care. Extracutaneous findings include dental, neurologic, and ocular anomalies. Requiring increased frequency of follow up by specialists during early childhood.

Infantile hemangioma with minimal or arrested growth as the skin manifestation of PHACE syndrome.

Infantile hemangiomas with minimal or arrested growth are vascular tumors with a proliferative component involving <25% of their total surface area. They are commonly described as localized lesions and are mainly located on the lower body. Little has been described about segmental forms on the face and their associations with PHACE syndrome. We carried out a multicenter, retrospective, case-series study involving 5 hospitals in Spain. Information was collected on cases of PHACE syndrome featuring infantile hemangiomas with minimal or arrested growth. The frontotemporal and maxillary areas were the most frequently involved sites in our series. The upper eyelid and upper lip were the 2 locations most frequently associated with proliferation and ulceration. Four patients experienced spontaneous resolution, and the rest had a very good cosmetic outcome with oral treatment. Cerebral and cervical arterial anomalies were the most frequent extracutaneous findings associated with PHACE, followed by cerebral and ocular anomalies. Some unique associated disorders were fructose intolerance and retinoblastoma. We present the largest case series of segmental facial infantile hemangiomas with minimal or arrested growth in PHACE syndrome and emphasize the importance of recognizing these lesions in early infancy, because they can indicate PHACE syndrome. The data presented suggest that infantile hemangiomas with minimal or arrested growth-associated PHACE syndrome does not seem to differ significantly from PHACE syndrome with classic infantile hemangiomas, and thus the same recommendations for diagnosis, management, and therapy should be followed. Future studies with more patients could contribute to enlighten this specific subset.

Cutaneous Polyarteritis Nodosa (cPAN) in ab 5 Years Old Girl

Polyarteritis nodosa is a rare form of systemic vasculitis. Cutaneous polyarteritis nodosa (cPAN) is subtype of systemic PAN which predominantly affects the skin, extra-cutaneous findings include fever, malaise, myalgias, arthralgias, and neuropathy. The true incidence of cutaneous PAN is unknown. cPAN is recognized as a separate entity and is essentially a benign disorder which should be distinguished from systemic PAN, as the clinical course and management of the two conditions is different. In this case report, we have described a patient with fever and gangrene of both hands and feet. The patient underwent a very extensive workup in order to determine the cause of her condition, which finally turned out cPAN on skin biopsy

Pigmentary Mosaicism with Myxomatous Mitral Valve Disease and Various Extra Cutaneous Findings

Pigmentary Mosaicism with Myxomatous Mitral Valve Disease and Various Extra Cutaneous Findings