Phacomatosis pigmentokeratotica--a patient with hypophosphatemic rickets.

The epidermal naevus syndrome (ENS) is a sporadic condition characterized by congenital epidermal naevi associated with anomalies in other organ systems, most commonly the central nervous system and skeleton. We report a case of ENS presenting hypophosphataemic rickets resistant to traditional therapeutic agents.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis.

Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1-q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor beta (OSMRbeta), in three families. OSMRbeta is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching.

The role of intramolecular epitope spreading in the pathogenesis of endemic pemphigus foliaceus (fogo selvagem).

We report here a relationship between intramolecular epitope spreading and the clinical onset of the endemic form of pemphigus foliaceus in a Brazilian community with a high prevalence and incidence of the disease. Also known as Fogo Selvagem (FS), this disease is characterized by severe skin blistering and pathogenic anti-desmoglein-1 (Dsg1) autoantibodies. These autoantibodies bind the Dsg1 ectodomain and trigger keratinocyte cell detachment, the hallmark of FS. We show that (a) sera from FS patients in the preclinical stage recognized epitopes on the COOH-terminal EC5 domain of Dsg1, (b) disease onset was associated with the emergence of antibodies specific for epitopes on the NH2-terminal EC1 and EC2 domains, (c) all sera from FS patients with active disease recognized the EC1 and/or EC2 domains, and (d) sera from FS patients in remission showed reactivity restricted to EC5. These results suggest that anti-Dsg1 autoantibodies in FS are initially raised against the COOH-terminal EC5 domain of Dsg1 in individuals without skin disease; in genetically predisposed subjects the autoimmune response may then undergo intramolecular epitope spreading toward epitopes on the NH2-terminal EC1 and EC2 domains of Dsg1 leading to disease onset. Moreover, intramolecular epitope spreading may also modulate remissions and relapses of FS.

Coati (Nasua nasua) attacks on humans: case report.

Coatis [including Nasua nasua, the ring-tailed coati], are medium-sized mammals widely distributed in the Americas. They are social animals, whose normal diet includes insects, fruits, and small vertebrates, and rarely prey on larger sized animals. There are, to our knowledge, no reports in the medical literature of attacks on humans. This report describes a coati attack on 2 children in their home. The children sustained deep scratches and bites. The animal may have injured the humans in a defensive strike, but motivation for attack was uncertain. Coati attacks may occur in places where there is interaction between these mammals and humans.

A Lutzomyia longipalpis Salivary Protein Induces Cross-Reactive Antibodies to Pemphigus Autoantigen Desmoglein 1.

Fogo selvagem (FS) is a blistering skin disease caused by pathogenic IgG4 autoantibodies to desmoglein 1 (DSG1). Preclinical FS and leishmaniasis are endemic to certain regions of Brazil and exhibit nonpathogenic anti-DSG1 antibodies. Recurring bites from Lutzomyia longipalpis, the sand fly vector of leishmaniasis, immunize individuals with L. longipalpis salivary antigens LJM17 and LJM11. We measured the antibody responses to LJM17, LJM11, and DSG1 in normal settlers and patients with FS from an endemic focus of FS and nonendemic control populations. We also immunized mice with these antigens and assessed the IgG response. Healthy individuals and patients with FS from endemic areas had significantly higher values of IgG4 anti-LJM17 antibodies than nonendemic controls (P < 0.001 for both). The levels of IgG anti-DSG1 and IgG4 anti-LJM17 and anti-LJM11 antibodies correlated positively in normal settlers and patients with FS. Mice immunized with recombinant LJM17 produced IgG1 antibodies (human IgG4 homolog) that strongly cross-reacted with recombinant DSG1; these IgG1 antibodies were inhibited by LJM17, LJM11, and DSG1 in a dose-dependent manner. However, they did not bind human or mouse epidermis by indirect immunofluorescence. Lastly, we identified short-sequence homologies of surface-exposed residues within the human DSG1 ectodomain and LJM17. Inoculation by LJM17 from L. longipalpis-elicited DSG1-cross-reactive IgG4 antibodies may lead to FS in genetically predisposed individuals.

Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus foliaceus - Brazilian Society of Dermatology.

Pemphigus are intraepidermal autoimmune bullous dermatoses that occur with lesions on the skin and / or mucous membranes. The most frequent types are pemphigus vulgaris and pemphigus foliaceus (classic and endemic). This consensus aims to present a complete and updated review of the treatment of these two more frequent forms of pemphigus, based on the literature and the personal experience of the authors. In moderate and severe cases of pemphigus vulgaris and foliaceus, systemic corticosteroid therapy (prednisone or prednisolone) is the treatment of choice. Adjuvant drugs, usually immunosuppressive drugs (azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide) may be prescribed as corticosteroid sparers in refractory cases or with contraindications to corticosteroids to minimize side effects. In severe and nonresponsive cases, corticosteroids in the form of intravenous pulse therapy, immunoglobulin and plasmapheresis / immunoadsorption can be administered. Immunobiological drugs, particularly rituximab, appear as a promising alternative. For milder cases, smaller doses of oral corticosteroid, dapsone and topical corticosteroids are options. At the end flowcharts are presented as suggestions for a therapeutic approach for patients with pemphigus vulgaris and pemphigus foliaceus.

Do you know this syndrome? Harlequin syndrome.

Harlequin syndrome is a rare condition in which one half of the face fails to flush and sweat due to damage of the sympathetic fibers on the ipsilateral side. The majority of cases are idiopathic, but may be iatrogenic or caused by space-occupying lesions or brainstem infarction. We report a case of idiopathic harlequin syndrome in a 34-year-old man with a 5-month history of unilateral facial flushing and sweating after exercise. Despite the rarity of this syndrome, dermatologists should be aware of this condition in order to diagnose properly and provide multidisciplinary assistance.

Fogo selvagem: endemic pemphigus foliaceus.

Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.

Cutaneous leiomyosarcoma on the face.

Leiomyosarcoma is a rare skin tumor, most common in white men in the fifth to eighth decades of life. Primary tumors are classified in dermal or subcutaneous, that differ by clinical and prognostic features. They may appear on any site of the body, but are rare on the face. A 54-year-old female was admitted with a 5cm exophytic nodular lesion of 8 months duration on the right cheek, site of previous chronic radiodermatitis. Histopathology revealed spindle-shaped cell neoplasia, positive for smooth muscle actin on immunohistochemistry. Cutaneous leiomyosarcomas on the face are rare and may occur in previously irradiated areas. Immunohistochemistry is mandatory for an accurate diagnosis. Its similarity with other tumors may complicate the diagnosis, with delay expansion of the tumor.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

Abstract This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Divergent Specificity Development of IgG1 and IgG4 Autoantibodies in Endemic Pemphigus Foliaceus (Fogo Selvagem).

We have shown that although the IgG response in fogo selvagem (FS) is mainly restricted to desmoglein (Dsg) 1, other keratinocyte cadherins are also targeted by FS patients and healthy control subjects living in the endemic region of Limão Verde, Brazil (endemic controls). Evaluating nonpathogenic IgG1 and pathogenic IgG4 subclass responses to desmosomal proteins may reveal important differences between pathogenic and nonpathogenic responses, and how these differences relate to the pathogenic IgG4 response and resultant FS. In this study, we tested by ELISA >100 sera from each FS patient, endemic control, and nonendemic control for IgG1 and IgG4 autoantibodies to keratinocyte cadherins besides Dsg1. IgG1 and IgG4 subclass responses in endemic controls are highly correlated between Dsg1 and other keratinocyte cadherins. This correlation persists in the IgG1 response among FS patients, but diminishes in IgG4 response, suggesting that IgG1 binds highly conserved linear epitopes among cadherins, whereas IgG4 binds mainly specific conformational epitopes on Dsg1. A confirmatory test comparing serum samples of 11 individuals before and after their FS onset substantiated our findings that IgG1 recognizes primarily linear epitopes on Dsg1 both before and after disease onset, whereas IgG4 recognizes primarily linear epitopes before disease onset, but recognizes more conformational epitopes on Dsg1 after the onset of disease. This study may provide a mechanism by which a specificity convergence of the IgG4 response to unique Dsg1 epitopes, most likely conformational pathogenic epitopes, leads to the onset of FS disease.

Prevalence of anti-desmoglein-3 antibodies in endemic regions of Fogo selvagem in Brazil.

Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a previously identified focus of disease. Autoantibodies against desmoglein 3 (Dsg3) have also been detected in sera from patients with FS. In an effort to further characterize the serological, geographical, and clinical epidemiology of the disease, we sought to determine the prevalence of anti-Dsg3 autoantibodies in sera from normal subjects living outside of and in an endemic area using an ELISA. Anti-Dsg3 antibodies were detected in 53 of 146 normal subjects from Limao Verde (36%), and in eight of 140 normal subjects from surrounding areas (6%). A significant trend was observed in the proportion of positive tests relative to distance from the endemic area (P < 0.001). Our seroepidemiological observations support the concept that the likely environmental trigger of the antibody response in FS is located in this endemic area, and that the population at risk to develop FS may also be at risk to develop an endemic form of pemphigus vulgaris as reported by our co-investigators from Brasilia.

Disseminated cutaneous atypical mycobacteriosis by M. chelonae after sclerotherapy of varicose veins in a immunocompetent patient: a case report.

Atypical mycobacteria are saprophytic organisms not transmitted from person to person, which affect mainly immunosuppressed but also immunocompetent individuals. We present a case of atypical mycobacteriosis after a vascular procedure, with widespread cutaneous lesions associated with polyarthralgia. Mycobacterium chelonae was identified by the polymerase chain reaction (PCR) method. The patient showed improvement after treatment with three antibiotics. Mycobacterium chelonae causes skin lesions after invasive procedures. The clinical form depends on the immune state of the host and on the entry points. The diagnosis is based essentially on culture and the mycobacteria is identified by PCR. We highlight the importance of investigating atypical mycobacteriosis when faced with granulomatous lesions associated with a history of invasive procedures.

Rendu-Osler-Weber syndrome: dermatological approach.

The Rendu-Osler-Weber syndrome is a rare systemic fibrovascular dysplasia, recognized by mucocutaneous telangiectasias, arteriovenous malformations, epistaxis and family history. Recurrent bleeding, hypoxemia, congestive heart failure, portosystemic encephalopathy, and symptoms related to angiodysplasia of the central nervous system may occur. Since the treatment is based on supportive measures, early recognition is of utmost importance. This article reports the case of a 53-year-old male patient who presented telangiectasias on fingers, oral cavity and nasal mucosa for 10 years, with a history of recurrent epistaxis of varying severity since childhood. Mother, sister and daughter have similar lesions.

Brazilian spotted fever: the importance of dermatological signs for early diagnosis.

Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis. We report a case of Brazilian spotted fever in a 19-year-old patient who presented maculopapular exanthema in the palmar region and upper limbs, lymphadenopathy, fever, chills, headache, conjunctival hyperemia, nausea, vomiting, dyspnea, myalgia, developing neurological signs and abdominal pain. He was treated with doxycycline with clinical improvement. We emphasize the importance of the recognition of this disease by dermatologists as cutaneous manifestations are the key findings to establish early diagnosis and prevent complications.

Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma.

BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors.

Anti-desmoglein-1 antibodies in onchocerciasis, leishmaniasis and Chagas disease suggest a possible etiological link to Fogo selvagem.

Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem (FS) are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.