The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis.

Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were significantly different (p < 0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure.

Lucio phenomenon of leprosy LL type on pregnancy: A Rare Case.

Introduction: Lucio phenomenon is a rare type of reaction in untreated, diffusely infiltrative form of lepromatous leprosy type, characterised with ulcerative type of skin lesions. Case: A 29 year old Indonesian female, 7th months primigravida with a four-month history of painful scarlet spots that darken and ulcerate on both of her hands and legs. The patient was experiencing fever. The patient's eyebrows were lost and her earlobes were thickened 3 years ago. Slit-skin smear: BI 6þ,MI 7%. Histopathology: Lucio phenomenon. PCR detecting M. leprae DNA on skin lesion and amniotic fluid: positive; umbilical cord membrane and umbilical cord: negative. Anti-PGL-1 IgM and IgG: patient: 4,854 U/mL and 1,061 U/mL, respectively; 5 month-old baby: 5 U/mL and 1,724 U/mL, respectively; 1 year-old baby: 0 U/mL and 3 U/mL, respectively. Conclusion: Placenta is considered a protective barrier toward feto-maternal transmission of M. leprae. The baby had the passive antibody to M. leprae from the mother's blood transmitted through the umbilical cord as demonstrated by the presence of anti-PGL-1 IgG antibody.

Bullous erythema nodosum leprosum manifesting in the post partum period with unusual features.

A 30 year old woman who presented with multiple numb patches on the body was initially diagnosed as borderline lepromatous leprosy and started on multidrug therapy for leprosy. She had an episode of Type 1 reaction during the fifth month of pregnancy. After delivery, she stopped therapy fearing harm to her child and developed an episode of Type 2 reaction. The reaction was unusual in that bullous lesions developed over previous leprosy patches which had initially become indurated, with associated neuritis. Histopathology revealed bullae with intense neutrophilic reaction and strong positivity for acid fast bacilli. There was no response to steroid therapy which was started for the reaction. Thalidomide had to be prescribed after stopping lactation by medical means. She responded dramatically to Thalidomide with regression of cutaneous lesions and neuritis. This patient is being reported as a very unusual manifestation of bullous erythema nodosum leprosum in the postpartum period responding dramatically to thalidomide.

Gestação e hanseníase: uma associação de risco nos serviços de saúde / Pregnancy and leprosy: a association of risk in the health services

Estudo descritivo, com abordagem quantitativa. Teve por objetivos levantar aspectos sociodemográficos de um grupo de mulheres com hanseníase, em idade fértil; verificar características clínicas da hanseníase no mesmo grupo; e identificar risco de exposição de mulheres em tratamento de hanseníase a uma gestação, bem como a prática anticoncepcional destas. Os dados foram coletados em outubro de 2006, em um Centro de Referência em Dermatologia Sanitária, localizado em Fortaleza-CE. Participaram 80 mulheres portadoras de hanseníase, em idade fértil (30% do total das cadastra-das no serviço). Foram excluídas mulheres histerectomizadas e menopausadas. Destas, 10 (12,5%) estavam na faixa etária da adolescência; 38 (47,5%) eram casadas ou viviam de forma consensual; 16 (20%) mantinham o desejo de conceber; 39 (48,8%) utilizavam métodos anticoncepcionais, sendo que 9 (23%) faziam sem a orientação de um profissional; e 66 (82,5%) desconheciam os efeitos da gestação na hanseníase. Oito (10%) manifestaram a hanseníase na gravidez, 32 (40%) apresentaram reações hansênicas e 4 (13%) fizeram uso de Talidomida (fármaco teratogênico em mulheres em idade fértil). Com base nos resultados encontrados podemos afirmar que mulheres portadoras de hanseníase em tratamento, ficam expostas a uma gravidez de alto risco, aumentando as chances e a gravidade das reações hansênicas e das recidivas, o que deve ser atenção adequada em anticoncepção.

Descriptive study with quantitative approach. Aimed to raise sociodemographic aspects from a group of wom-en with leprosy in childbearing; verify clinical character-istics of leprosy in the same group, and identify expo-sure of pregnant women in treatment for leprosy and the contraceptive practice of these. Data were collected in October 2006 in a Reference Center in Sanitary Der-matology, located in Fortaleza, Brazil. Participated 80 women with leprosy, in childbearing age (30% of total enrolled in the service). Were excluded hysterectomized women and postmenopausal. Of these, 10 (12.5%) were aged teens, 38 (47.5%) were married or living in a con-sensual manner, 16 (20%) had the desire to conceive, 39 (48.8%) used contraceptive methods, and 9 (23%) were without the guidance of a professional, and 66 (82.5%) ignored the effects of pregnancy on leprosy. Eight (10%) had leprosy in pregnancy, 32 (40%) had reactions and 4 (13%) made use of Thalidomide (drug teratogenic in women of childbearing age). Based on these results we can affirm that women with leprosy treatment, are exposed to a high risk pregnancy, increasing the likeli-hood and severity of the reactions and relapses, which should be mitigated by proper care in contraception.

Pigmentary demarcation lines on the face in Saudi women.

BACKGROUND: Pigmentary demarcation lines (PDL) are physiological abrupt transition lines between hyperpigmented skin and lighter areas. Recent evidence suggests that they involve the face. AIMS: To survey facial PDL in Saudi females referred to general dermatology clinics for various complaints and determine any associated risks. METHODS: Screening for facial lines was done in general dermatology clinics over a year. Whenever a patient was found to have facial PDL, a detailed questionnaire and examination were undertaken. RESULTS: Out of 1033 patients screened, 144 patients (14%) were found to have at least one of the facial PDLs. The median age of onset was 16 years. The most common line was F with 76 patients (53%). Family history was positive in 51 patients (35%). CONCLUSION: Facial PDL is a common and chronic pigmentary problem in Saudi women. It should be recognized and differentiated from other similar diseases like melasma. A significant proportion of patients have a milder presentation.

Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine.

Two multigravidae aged 27 and 29 years, with previous uneventful pregnancies, second being psoriatic, reported at 24 and 28 weeks of pregnancies, with generalized pustular lesions. Laboratory findings, including serum calcium were normal. Ultrasonography showed normal fetal growth. Histopathology confirmed pustular psoriasis. Patients were put on cyclosporine 3 mg/ kg weight/ day after failure of an initial systemic steroid. Blood pressure, pulse, and fetal heart sounds were recorded every 12 hours, and ultrasonography and blood parameters, biweekly. Cyclosporine was tapered and stopped after delivery of two healthy babies at 38 weeks. We conclude that cyclosporine can be an option in the management of pustular psoriasis of pregnancy or psoriasis with pustulation in pregnancy.

Periorbital melanosis is an extension of pigmentary demarcation line-F on face.

BACKGROUND: To date, periorbital melanosis is an ill-defined entity. The condition has been stated to be darkening of the skin around the eyes, dark circles, infraorbital darkening and so on. AIMS: This study was aimed at exploring the nature of pigmentation in periorbital melanosis. METHODS: One hundred consecutive patients of periorbital melanosis were examined and investigated to define periorbital melanosis. Extent of periorbital melanosis was determined by clinical examination. Wood's lamp examination was performed in all the patients to determine the depth of pigmentation. A 2-mm punch biopsy was carried out in 17 of 100 patients. RESULTS: In 92 (92%) patients periorbital melanosis was an extension of pigmentary demarcation line over the face (PDL-F). CONCLUSION: Periorbital melanosis and pigmentary demarcation line of the face are not two different conditions; rather they are two different manifestations of the same disease.

A clinical study of skin changes in pregnancy.

BACKGROUND: During pregnancy profound immunologic, metabolic, endocrine and vascular changes occur, that are responsible for the changes of the skin and its appendages, both physiologic and pathologic. AIMS: We undertook a clinical study to find out the frequency and pattern of skin changes in pregnant women. METHODS: All consecutive pregnant women were included in the study. RESULTS: A total of 607 pregnant women were included in this study. Of these, 303 (49.9%) pregnant women were primigravida and 304 (51.1%) were multigravida. Skin changes grouped into: physiological changes (all cases), specific dermatoses (22 cases) and other dermatoses affected by pregnancy (125 cases). Most common physiological changes were pigmentary alterations seen in 555 (91.4%) followed by striae seen in 484 (79.7%) cases. Of the various specific dermatoses of pregnancy, pruritic urticarial papules and plaques of pregnancy (PUPPP) was the most common disorder (14 cases) followed by pruritus gravidarum (5 cases). The most common dermatoses affected by pregnancy were candidal vaginitis (17 cases), acne vulgaris (15 cases), skin tags (15 cases), eczemas (14 cases). CONCLUSION: This study brings into focus various skin changes during pregnancy in south India.

Pele na gestacão / Skin in pregnancy

As manifestacões cutâneas durante a gravidez correspondem a alteracões fisiológicas, dermatoses próprias do período gestacional ou doencas pré-existentes. O penfigóide gestacional, a erupcão polimorfa da gravidez, a foliculite pruriginosa, o prurigo da gravidez e o prurido gravídico são considerados dermatoses próprias da gestacão. Uma forma de psoríase pustulosa grave, o impetigo herpetiforme, está descrito na gestacão. As lesões cutâneas da artrite psoriásica, do lúpus eritematoso, da dermatopolimiosite e os pênfigos podem piorar na gravidez. O eritema nodoso e o eritema nodoso hanseniano podem ser desencadeados pela gravidez. O tratamento deve considerar os riscos e benefícios para a mãe e o concepto.

Administración de fármacos utilizados en dermatología durante el embarazo y la lactancia (I) / Administration of drugs used in dermatology during pregnancy and breastfeeding (I)

No disponible

S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide.

In July 1998, the US Food and Drug Administration approved the marketing of thalidomide for the treatment of cutaneous manifestations of erythema nodosum leprosum. To ensure that fetal exposure to this teratogenic agent does not occur, the manufacturer has instituted a comprehensive program to control prescribing, dispensing, and use of the drug. This program, known as the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S. [Celgene Corporation, Warren, New Jersey]), is based in part on experience gained with other drugs--specifically isotretinoin and clozapine--that offer important clinical benefits but carry the potential for serious harm. To achieve its goal of the lowest possible incidence of drug-associated teratogenicity, the S.T.E.P.S. program uses a three-pronged approach: (1) controlling access to the drug; (2) educating prescribers, pharmacists, and patients; and (3) monitoring compliance. Clinicians who wish to prescribe thalidomide must be registered in the S.T.E.P.S. Prescriber Registry and agree to prescribe the drug in accordance with S.T.E.P.S. patient eligibility criteria and monitoring procedures. Pharmacies must also register and agree to comply with patient identification and monitoring criteria. Finally, patients receive visual aids, including a videotape, written material, and verbal counseling about the benefits and risks of thalidomide therapy, the importance of not becoming pregnant during therapy, and the types of contraception required (including emergency contraception) and their availability. Women of childbearing potential must agree to undergo pregnancy testing before starting therapy and on a regular schedule during therapy. All patients must agree to complete a confidential survey about their compliance with contraception, testing, and drug therapy. The manufacturer is monitoring survey results and outcome data and is prepared to make whatever modifications to the S.T.E.P.S. program are necessary to ensure its effectiveness. In addition to minimizing the potential risk for fetal harm associated with thalidomide therapy, the S.T.E.P.S. program may provide a model for future cases in which a drug offers compelling benefits but poses profound risks unless its distribution is carefully controlled.