Update on Neonatal Isolated Hyperthyrotropinemia: A Systematic Review

The purpose of this paper was to systematically summarize the published literature on neonatal isolated hyperthyrotropinemia (HTT), with a focus on prevalence, L-T4 management, re-evaluation of thyroid function during infancy or childhood, etiology including genetic variation, thyroid imaging tests, and developmental outcome. Electronic and manual searches were conducted for relevant publications, and a total of 46 articles were included in this systematic review. The overall prevalence of neonatal HTT was estimated at 0.06%. The occurrence of abnormal imaging tests was found to be higher in the persistent than in the transient condition. A continuous spectrum of thyroid impairment severity can occur because of genetic factors, environmental factors, or a combination of the two. Excessive or insufficient iodine levels were found in 46% and 16% of infants, respectively. Thirty-five different genetic variants have been found in three genes in 37 patients with neonatal HTT of different ethnic backgrounds extracted from studies with variable design. In general, genetic variants reported in the TSHR gene, the most auspicious candidate gene for HTT, may explain the phenotype of the patients. Many practitioners elect to treat infants with HTT to prevent any possible adverse developmental effects. Most patients with thyroid abnormalities and/or carrying monoallelic or biallelic genetic variants have received L-T4 treatment. For all those neonates on treatment with L-T4, it is essential to ensure follow-up until 2 or 3 years of age and to conduct medically supervised trial-off therapy when warranted. TSH levels were found to be elevated following cessation of therapy in 44% of children. Withdrawal of treatment was judged as unsuccessful, and medication was restarted, in 78% of cases. Finally, data extracted from nine studies showed that none of the 94 included patients proved to have a poor developmental outcome (0/94). Among subjects presenting with normal cognitive performance, 82% of cases have received L-T4 therapy. Until now, the precise neurodevelopmental risks posed by mild disease remain uncertain.Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Tellechea, Mariana Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Pityriasis Lichenoides et Varioliformis Acuta: Case Report and Review of the Literature

We report a case of a 63-year-old man hospitalized for a polymorphous generalized eruption consisting of maculopapules with peripheral scaling, vesicopustules, and ulceronecrotic and crusted lesions measuring 5–20 mm, localized on his trunk and extremities, particularly exuberant in the flexural area. Histopathology showed necrotic keratinocytes with exocytosis of red blood cells and lymphocytes and a dermal perivascular and periadnexal inflammatory infiltrate, composed of CD8+/CD4–/CD30– T cells, indicating the clinical diagnosis of pityriasis lichenoides et varioliformis acuta. He was treated with erythromycin and methylprednisolone reduced gradually over 5 months, with a slow but complete response; the patient was without lesions after 2 years of follow-up. The authors want to remind of this rare entity which may present difficulties in diagnosis and therapy

PLASMOCITOMA CUTÂNEO METASTÁTICO EM DOENTE COM MIELOMA MÚLTIPLO

Introduction: In multiple myeloma, the cutaneous lesions are rare and usually occur in late stages of MM as a reflection of increased tumour cell burden. Case report: The authors present the case of a 66 year-old woman with IgG lambda multiple myeloma that, after 16 months and apparently under control haematological, developed a tender and firm erythemato-violaceous plaque, on the back of the right thigh. A diagnosis of cutaneous plasmocytoma was confirmed by skin biopsy. Local radiotherapy induced a complete regression of skin lesion, but the patient died 4 months later, duo to uncontrolled multiple myeloma. Discussion: Secondary cutaneous plasmocytoma usually arise from direct spread from underlying bone, manifest as erythematous to violaceous infiltrated nodules or plaques, are extremely rare and indicate a poor prognosis, as in our case. The presentation as an erysipela-like lesion with no underlying bone disease is even rarer.KEYWORDS – Multiple myeloma; Plasmacytoma; Skin neoplasms/secondary.Introdução: No mieloma múltiplo as lesões cutâneas são raras e ocorrem em fases tardias da doença, como um reflexo da elevada carga tumoral. Caso clínico: Os autores relatam o caso de uma doente de 66 anos com mieloma múltiplo IgG lambda que, após 16 meses de evolução e aparentemente sob controlo hematológico, desenvolveu uma placa eritemato-violácea, dolorosa e de consistência dura, atingindo a face posterior da coxa direita. A biopsia cutânea confirmou o diagnóstico de plasmocitoma cutâneo. Radioterapia local induziu regressão completa da lesão cutânea, no entanto a doente faleceu 4 meses depois. Discussão: O plasmocitoma cutâneo secundário surge habitualmente por contiguidade a partir de lesões ósseas subjacentes, manifesta-se por placas ou nódulos eritemato-violáceos infiltrados, são extremamente raros e indicam um prognóstico desfavorável como no nosso caso. A apresentação da lesão como erisipela-like sem doença óssea subjacente é ainda mais raro.PALAVRAS-CHAVE – Mieloma múltiplo; Plasmacitoma; Neoplasias da pele

DERMATITE HERPETIFORME EM IDADE PEDIÁTRICA – UM DIAGNÓSTICO A TER EM CONTA

Introduction: Dermatitis herpetiformis is a chronic, pruritic, polymorphous dermatosis, considered the cutaneous equivalent of coeliac disease. In pediatric patients, differential diagnosis with other more common dermatosis makes this a challenging diagnosis.Case Report: We present the case of an 8-year old male patient, with polymorphous, pruritic lesions on the extensor surfaces of limbs, evolving for 2 years. Lesional skin biopsy showed neutrophils on the tips of the dermal papillae, and direct immunofluorescence of perilesional skin demonstrated granular deposits of IgA also on the tips of the dermal papillae, establishing the diagnosis of dermatitis herpetiformis. Subsequent studies confirmed the association to celiac disease and the adoption of a gluten-free diet led to the clinical resolution of both cutaneous lesions and enteropathy.Introdução: A Dermatite herpetiforme é uma dermatose crónica, pruriginosa e polimórfica considerada o equivalente cutâneo da doença celíaca. Na população pediátrica é, com frequência, um diagnóstico difícil de evocar, quer pela sua raridade quer pelo polimorfismo das lesões cutâneas.Caso Clínico: Apresentamos um doente do sexo masculino de 8 anos, com lesões polimorfas nas superfícies extensoras dos membros evoluindo há 2 anos. A biopsia cutânea lesional demonstrou neutrófilos nas papilas dérmicas e a imunofluorescência directa peri-lesional revelou depósitos granulosos de IgA nas papilas dérmicas, estabelecendo o diagnóstico de dermatite herpetiforme. Estudo complementar subsequente confirmou a associação a doença celíaca e a adopção de uma dieta sem glúten levou à resolução clínica cutânea e da enteropatia

HISTIOCITOSE CEFÁLICA BENIGNA

Benign cephalic histiocytosis is a type of non-Langerhans histiocytitic disorder. Of unknown etiology, is a self-healing disease, arising in childhood and is characterized by papular lesions primarily affecting the face. We describe a 10-month-old girl who presented with 6 months of evolution, yellow-red papules asymptomatic, on her face. The histological and immunohistochemical study showed the presence of a diffuse infiltration of histiocytes, throu- ghout the dermis, negative for the protein S100 and CD1a and positive for CD68. Given the diagnosis of benign cepha- lic histiocytosis, we chose an expectant attitude verifying complete regression after one year of follow-up. Since its description by Gianotti, et al. in 1971, only 40 cases were reported in the literature. KEYWORDS – Histiocytosis; Non-Langerhans-cell; Facial dermatoses; Skin diseases. A histiocitose cefálica benigna faz parte do grupo das histiocitoses de células não-Langerhans. De etio- logia desconhecida, é uma doença autolimitada, que surge na infância e se caracteriza por lesões papulosas que afetam fundamentalmente a face. Descrevemos o caso clínico de uma criança de 10 meses de idade que apresentava desde há 6 meses lesões papu- losas, eritemato-amareladas, assintomáticas e de localização exclusiva à face. O estudo histológico e imuno-histo- químico revelou a presença de um infiltrado difuso de histiócitos em toda a derme, negativo para a proteína S100 e CD1a e positivo para CD68. Perante o diagnóstico de histiocitose cefálica benigna, optou-se por uma atitude expec- tante verificando-se regressão clínica completa após um ano de seguimento. Desde a sua descrição por Gianotti, et al. em 1971, apenas 40 casos foram descritos na literatura.PALAVRAS-CHAVE – Histiocitose cefálica benigna; Histiocitoses de células não-Langerhans; Doença autolimitada.

NODULAR MALIGNANT MELANOMA - OR MAYBE NOT?

O poroma écrino é um tumor anexial benigno relativamente raro com múltiplas apresentações clínicas, mimetizadoras de várias outras neoplasias cutâneas. A sua forma pigmentada é pouco usual, estando descrita sobretudo na raça não caucasóide e poupando as extremidades. Os autores apresentam o caso clínico de uma doente com uma lesão tumoral pigmentada localizada no ombro esquerdo que evocou um diagnóstico inicial de melanoma maligno nodular mas cujo estudo histopatológico revelou tratar-se da variante pigmentada do poroma écrino. A lesão foi excisada e encontra-se sem recorrência até à data, com um período de seguimento de seis meses.Eccrine poroma is a relatively rare benign adnexal tumor with multiple clinical presentations, mimicking several other cutaneous neoplasms. The pigmented form is uncommon and usually located in nonacral sites in non-white patients. The authors present the case of a patient with a pigmented tumoural lesion on the left shoulder clinically thought to represent nodular malignant melanoma, but whose histopathology revealed a pigmented form of eccrine poroma. The lesion was surgically removed and no recurrence was seen after six months of follow-up

HIPERSENSIBILIDADE RETARDADA A HEPARINA DE BAIXO PESO MOLECULAR – QUE ALTERNATIVA À ANTICOAGULAÇÃO?

A 75 year-old obese patient was submitted to anticoagulant therapy for deep vein thrombosis (DVT) of the lower limb: classic intravenous heparin for 3 days and subcutaneous dalteparin for 10 days. Three days after the end of treatment the patient developed eczema-like plaques at the subcutaneous low-molecular-weight heparin (LMWH) injec- tion sites. Prick, intradermal and patch tests were performed using heparins and fondaparinux, and were inconclusive or negative at 30 minutes and at 48 hours, therefore, subcutaneous tests were than performed. At D3 and D7 intradermal tests were positive for fraxiparin, dalteparin and enoxaparin and subcutaneous tests were also positive at D5. All tests were negative for fondaparinux, considered a safe anticoagulant alternative. Allergy testing with several heparins and heparinoids is essential to confirm delayed hypersensitivity to LMWH and identify safe alternatives in case of future need for anticoagulation, as in this patient with risk factors for DVT.KEYWORDS – Anticoagulants; Hypersensitivity, Delayed; Heparin, Low-Molecular-Weight; Drug Eruptions; Skin Tests.Um doente de 75 anos de idade, obeso, realizou terapêutica anticoagulante por trombose venosa profunda (TVP) do membro inferior: heparina clássica endovenosa durante 3 dias e dalteparina subcutânea durante 10 dias. Três dias depois do término do tratamento o doente é observado por placas eczematiformes nos locais de administração da heparina de baixo peso molecular (HBPM). Os testes epicutâneos, prick, intradérmicos e subcutâneos realizados se- quencialmente com várias HBPM e fondaparinux foram negativos nas leituras imediatas e às 48h. Às 72 horas sugiram lesões eczematiformes nos testes intradérmicos e subcutâneos à enoxaparina, fraxiparina e dalteparina, confirmando o diagnóstico de hipersensibilidade retardada a HBPM. Os testes com o fondaparinux foram negativos, considerando-o uma alternativa anticoagulante segura. Os testes epicutâneos revelaram discreta reacção em D7 apenas à dalteparina e fraxiparina. Os testes de alergia, sobretudo os intradérmicos, com várias heparinas e heparinóides são essenciais para confirmar o diagnóstico e identificar alternativas seguras em caso de necessidade de anticoagulação futura, como neste doente com factores de risco para TVP.PALAVRAS-CHAVE – Anticoagulantes; Hipersensibilidade Retardada; Heparinas de baixo peso molecular; Erupções Cutâneas; Testes Cutâneos

ESCLEREDEMA ADULTORUM DE BUSCHKE – CASO CLÍNICO

Scleredema adultorum of Buschke (SAB) is a rare connective tissue disease characterized by non-pitting induration of the skin. Histologically there is thickening of the dermis with large collagen fibers separated by deposits of mucopolysaccharids. A 51-year-old male patient, with poorly controlled diabetes mellitus, progressively developed in a 5-year period, a di- ffuse cutaneous infiltration with ill-defined limits on the posterior neck, upper half of the trunk and proximal limbs, with marked skin stiffness and a significantly reduced mobility of the shoulder girdles and neck. The diagnosis of SAB was confirmed by histological examination. Other complementary exams did not reveal significant changes, allowing the diagnosis of the third subtype of SAB - diabeticorum. The patient was treated with phototherapy, initially with UVA1 without any benefit, and later with an experimental therapeutic modality of PUVA1 with significant clinical improvement, allowing the patient to dress himself.KEYWORDS – Scleredema Adultorum; Diabetes Mellitus; Phototherapy; PUVA Therapy.O Escleredema adultorum de Buschke (EAB) é uma doença rara do tecido conjuntivo caracterizada pelo endurecimento não depressível da pele. Histologicamente há espessamento da derme com fibras de colagénio espes- sadas separadas por mucopolissacáridos. Apresentamos um doente de 51 anos de idade, diabético insulinotratado com mau controlo metabólico, que referia um quadro com 5 anos de evolução de agravamento progressivo, caracte- rizado por infiltração cutânea difusa de limites mal definidos na região cervical posterior, metade superior do tronco e raiz dos membros, marcada diminuição da mobilidade cutânea e limitação funcional da charneira cervical e ombros. A hipótese de EAB foi confirmada pela histologia. Os restantes exames complementares de diagnóstico não revelaram alterações significativas, permitindo estabelecer o diagnóstico do subtipo III – diabeticorum. Iniciou fototerapia com radiação UVA1 sem qualquer benefício, e posteriormente uma terapêutica experimental com PUVA1, com melhoria clínica significativa, objectivável pela maior facilidade na realização de tarefas básicas como o vestir.PALAVRAS-CHAVE – Escleredema Adultorum; Escleredema Diabeticorum; Diabetes Mellitus; Fototerapia; PUVA

MERKEL CELL CARCINOMA – REPORT OF 7 CASES

Introdução: O carcinoma de células de Merkel é um carcinoma neuro-endócrino raro, agressivo que se manifesta geralmente nos idosos. Apresenta-se geralmente como um nódulo de crescimento rápido localizado preferencialmente na cabeça, pescoço ou membros. Tem elevada taxa de recorrência loco-regional e à distância. A excisão cirúrgica radical é o tratamento consensual e o papel da linfadenectomia, da radioterapia e da quimioterapia ainda não está claramente estabelecido. Material e Métodos: O objectivo deste estudo retrospectivo passou por avaliar os doentes com carcinoma de células de Merkel observados no nosso serviço entre os anos de 2000 e 2009 relativamente ao sexo, idade, raça, clínica, localização do tumor, estadio, neoplasias associadas, tratamento e evolução.Resultados: Os dados desta casuística foram concordantes com os da literatura, nomeadamente quanto à idade, associação com processos linfoproliferativos B, elevadas taxas de recidiva loco-regional e de mortalidade.Introduction: Merkel cell carcinoma is a rare, aggressive cutaneous neuroendocrine carcinoma that affects primarily elderly people. Patients present with a rapidly growing nodule, preferably located at the head, neck and limbs. Merkel cell carcinoma as a propensity for local recurrence and regional lymph node metastases and wide local excision is the initial consensual approach. The role of lymph node dissection, radiation therapy and chemotherapy is not yet clearly established. Material and Methods: The aim of this retrospective study was to evaluate Merkel cell carcinoma patients followed in our department between the years 2000 and 2009, regarding sex, age, race, clinical features, location, stage, associated malignancies, treatment and evolution.  Results: Our data are consistent with the literature, namely regarding age, associated lymphoproliferative disease and high local recurrence and mortality rates

Mechanisms involved in the development and healing of diabetic foot ulceration

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 \ub1 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-\u3b1, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs