Pyoderma gangrenosum: a review with special emphasis on Latin America literature

Abstract Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. Despite the existence of diagnostic criteria, there is no gold standard for diagnosis or treatment. In Latin America, recognizing and treating pyoderma gangrenosum is even more challenging since skin and soft tissue bacterial and non-bacterial infections are common mimickers. Therefore, this review aims to characterize reported cases of pyoderma gangrenosum in this region in order to assist in the assessment and management of this condition. Brazil, Mexico, Argentina, and Chile are the countries in Latin America that have reported the largest cohort of patients with this disease. The most frequent clinical presentation is the ulcerative form and the most frequently associated conditions are inflammatory bowel diseases, inflammatory arthropaties, and hematologic malignancies. The most common treatment modalities include systemic corticosteroids and cyclosporine. Other reported treatments are methotrexate, dapsone, and cyclophosphamide. Finally, the use of biological therapy is still limited in this region.

Oxidative stress in patients with endemic pemphigus foliaceus and healthy subjects with anti-desmoglein 1 antibodies

Abstract: Background: Previous studies have shown oxidative stress in pemphigus vulgaris and pemphigus foliaceus, nevertheless, it remains unknown whether a similar response is characteristic of endemic pemphigus foliaceus in Peru. Objectives: To determine the oxidative stress response in endemic pemphigus foliaceus patients and subjects with positive for anti-desmoglein1 antibodies (anti-dsg1) from endemic areas of Peru. Subjects and Methods: This is a cross-sectional study. The study population included 21 patients with Endemic Pemphigus foliaceus and 12 healthy subjects with anti-dsg1 antibodies from the Peruvian Amazon (Ucayali), as well as 30 healthy control subjects. Malondialdehyde, an indicator of lipid peroxidation by free radicals, was measured in serum. Results: We collected 21 cases of endemic pemphigus foliaceus, 15 of them with active chronic disease and 6 in clinical remission. Serum malondialdehyde values in patients with chronic active evolution and healthy subjects with anti-dsg1 antibodies were statistically higher than those of healthy controls (p<0.001). There was no significant difference between serum values of localized and generalized clinical forms. Study limitations: The main limitation of this present study is the small number of patients with endemic pemphigus and healthy subjects positive for desmoglein 1 antibodies. Conclusions: The increased serum levels of malondialdehyde in patients with chronic active endemic pemphigus foliaceus and healthy subjects from endemic areas with anti-dsg1 antibodies may suggest a contribution of systemic lipid peroxidation in the pathogenesis of endemic pemphigus foliaceus.

Pénfigo foliáceo endémico en Perú: una enfermedad autoinmune olvidada en la Amazonía / Effect of cyclosporine A in patients with complicated psoriasis

El pénfigo foliáceo endémico (PFE) es una enfermedad autoinmune de la piel endémica en áreas de la Amazonía peruana. Aunque no es una enfermedad frecuente, se presenta en personas de nivel socioeconómico bajo de áreas rurales de la amazonía, lo que dificulta su acceso a los servicios de salud y genera marginación, estigmatización y exclusión. Su difícil reconocimiento hace que el diagnóstico en los establecimientos del primer nivel de atención sea complicado Estos aspectos en su conjunto convierten al PFE en una enfermedad olvidada en la Amazonía. Es necesario capacitar al personal de salud médico y no médico de los establecimientos del primer nivel de atención de áreas endémicas para su reconocimiento y referencia a hospitales, donde puedan recibir manejo especializado. Las personas con PFE y otras enfermedades deberían beneficiarse del mejoramiento de los establecimientos de salud existentes en áreas rurales y alejadas del país como parte de la reforma de la salud.

The endemic pemphigus foliaceus (EPF) is an autoimmine skin disease endemic in areas of the Peruvian Amazon. Although not a common disease, occurs in people under rural areas of the Amazon, hindering their access to health services and generates marginalization, stigmatización and exclusion. Its difficult recognition makes diagnosis in the establishments of primary care is complicated. These aspects together make the EPF in a forgotten disease in the Amazon. It is necessary to train medical and non-medical health care establishments in the primary care areas endemic for recognition and referral to hospitals, where they con receive specialized management. People with EPF and other diseases should benefit from the improvement of existing facilities in rural and remote areas of the country as part of health reform health

Criptococosis / Cryptococcosis

La criptococosis es una infección micótica de distribución mundial, producida principalmente por el complejo Cryptococcus neoformans/Cryptococcus gattii (C. neoformans/C. gattii), ambos se encuentran ampliamente distribuidos en la naturaleza. C. neoformans afecta principalmente a personas inmunocomprometidas y C. gattii a pacientes inmunocompetentes expuestos a al nicho ecológico del hongo. Por lo general la puerta de entrada es por vía respiratoria y posteriormente se disemina a otras regiones del cuerpo, principalmente el sistema nervioso central. El diagnóstico se realiza por observación directa del hongo, estudios histopatológicos, aislamiento en cultivos y la presencia de antígeno capsular. Las manifestaciones cutáneas pueden ser por inoculación primaria a la piel, denominada criptococosis cutánea primaria o por diseminación hematógena como parte de una enfermedad sistémica, lo que se denomina criptococosis cutánea secundaria. Las principales diferencias son que en la primera existe un antecedente traumático previo, menor porcentaje de pacientes inmunodeprimidos y lesiones únicas o confinadas a las manos o áreas descubiertas. Aunque la incidencia de criptococosis ha disminuido con el tratamiento antirretroviral de gran actividad, aun es prevalente en regiones donde no se accede a este tratamiento, así mismo las manifestaciones cutáneas son difíciles de reconocer por lo que es importante que el médico considere este diagnóstico en pacientes con el virus de inmunodeficiencia humana o pacientes que antecedente traumático expuestos a la ecología del hongo como heces de palomas, tierra o madera en descomposición.

Cryptococcosis is an opportunistic fungal infection of worldwide distribution, mainly produced by the complex Cryptococcus neoformans / Cryptococcus gattii, both are widely distributed in nature, primarily affecting immunocompromised patients. Generally the gateway is through inhalation and later spread to other regions of the body, especially the central nervous system. The diagnosis is performed by direct observation of the fungus, histopathology, culture isolation and the presence of capsular antigen. Cutaneous manifestations may be for primary inoculation to the skin, called primary cutaneous cryptococcosis or for hematogenous spread as part of a systemic disease, which is called secondary cutaneous cryptococcosis. The main differences are a previous trauma, lower percentage of immunocompromised patients and single lesions confined to the hands or bare spots in the first case. Although the incidence of cryptococcosis has decreased with highly active antiretroviral therapy, is still prevalent in regions where there is not access to this treatment, also the skin manifestations are difficult to recognize what is important for the physician to consider this diagnosis in patients with the human immunodeficiency virus or patients with traumatic history exposed to ecology of the fungus as pigeon excreta, soil or decaying wood.

Cutaneous blastomycosis: a clue to a systemic disease / Blastomicose cutânea: um sinal de doença sistêmica

A 55-year-old male presented with back pain and slightly tender annular plaques with central ulceration on his face. A skin biopsy revealed scattered yeast with broad based buds. A CT scan of the abdomen revealed a pathologic T12 fracture. Tissue obtained from the spine confirmed budding yeasts. The patient was diagnosed with disseminated blastomycosis. The patient was treated with amphotericin and itraconazole and completely recovered. .

Paciente do sexo masculino, com 55 anos de idade, compareceu ao ambulatório com dores na costa e placas anulares ligeiramente sensíveis, com ulceração central na face. Uma biópsia cutânea revelou levedura disseminada, com brotos de base larga. A tomografia computadorizada do abdômen revelou uma fratura patológica da T12. Amostra de tecido obtido da coluna vertebral confirmou levedura em fase de brotamento. O paciente foi diagnosticado com blastomicose disseminada. Após tratamento com anfotericina e itraconazol, o paciente teve recuperação completa. .

Endemic pemphigus in the peruvian Amazon: epidemiology and risk factors for the development of complications during treatment / Pênfigo endêmico na Amazônia peruana: epidemiologia e fatores de risco para o desenvolvimento de complicações durante o tratamento

BACKGROUND: Pemphigus is an autoimmune blistering disease. According to a report, in areas of endemic pemphigus foliaceus (EPF) in Peru there are cases of pemphigus vulgaris with epidemiologic, clinical and histopathologic characteristics similar to those of "endemic pemphigus vulgaris" (EPV) in Brazil. OBJECTIVES: To determine the clinical and epidemiologic characteristics of endemic pemphigus and the risk factors of patients for developing complications during treatment. METHODS: A study was carried out from July 2003 to March 2008. The study population was 60 patients with EPF and 7 patients with EPV evaluated in hospitals and clinics in the Peruvian Amazon and Lima. A multivariate analysis was carried out using binary logistic regression. RESULTS: The average age of EPF patients was 31.4 years; 55% were men; 60% presented the generalized clinical variant. Non-compliance with the treatment was seen in 57.1% of the patients. Thirty-five percent presented complications (e.g. pyodermitis and pyelonephritis) during treatment. The risk factors for developing complications during treatment were non-compliance with the treatment and having the generalized clinical form. In the EPV group, the average age was 21.7 years; 71.4% were men. All patients presented with the mucocutaneous clinical variant and the initial presentation consisted of oral mucosa lesions; 71.4% presented complications during treatment, pyodermitis being the most frequent. CONCLUSIONS: Non-compliance with the treatment and the generalized clinical form are risk factors for the development of complications during treatment of patients with EPF. Peru indeed has EPV cases with epidemiologic characteristics similar to EPF. Living in a rural area may represent a risk factor for the development of complications during treatment of patients with EPV.

FUNDAMENTOS: O pênfigo é uma doença auto-imune bolhosa. Segundo um relatório, em áreas de pênfigo foliáceo endêmico no Peru há casos de pênfigo vulgar com características epidemiológicas, clínicas e histopatológicas semelhantes às do "pênfigo vulgar endêmico" no Brasil. OBJETIVOS: Determinar as características clínicas e epidemiológicas do pênfigo endêmico e os fatores de risco para o desenvolvimento de complicações durante o tratamento. MÉTODOS: Um estudo foi realizado de julho de 2003 a março de 2008. 60 doentes de pênfigo foliáceo endêmico e 7 de pênfigo vulgar endêmico foram avaliados em hospitais e clínicas na Amazônia peruana e em Lima. Uma análise multivariante foi feita usando regressão logística binária. RESULTADOS: A idade média dos doentes de pênfigo foliáceo endêmico foi 31,4 anos; 55% eram homens, 60% apresentavam a forma clínica generalizada. 57,1% nao cumpriram o tratamento. 35% apresentaram complicações (por exemplo, piodermites e pielonefrite). Os fatores de risco foram não cumprir o tratamento e ter a forma clínica generalizada. No grupo pênfigo vulgar endêmico, a idade média foi 21,7 anos; 71,4% eram homens. Todos os pacientes apresentavam a variante clínica mucocutânea e a apresentação inicial consistia de lesões da mucosa bucal; 71,4% apresentaram complicações durante o tratamento, piodermites sendo a mais freqüente. CONCLUSÕES: Não cumprir o tratamento e ter a forma clínica generalizada são fatores de risco para o desenvolvimento de complicações durante o tratamento de pênfigo foliáceo endêmico. Peru realmente tem casos de pênfigo vulgar endêmico com características epidemiológicas semelhantes às do pênfigo foliáceo endêmico. Viver numa área rural pode ser um fator de risco para o desenvolvimento de complicações.

Estudio comparativo del maíz morado (Zea mays L. ) y simvastatina en la reducción de lípidos séricos de pacientes diabéticos normotensos con dislipidemia / Comparative study of Peruvian purple corn (Zea mays L. ) and simvastatin in serum lipids reduction in normotense dyslipidemic diabetics

Objetivos: Determinar la eficacia de la administración del maíz morado (Zea mays) en la reducción de los niveles de lípidos séricos (efecto hipolipemiante) en pacientes diabéticos no hipertensos con dislipidemia. Comparar el efecto hipolipemiante del maíz morado con simvastatina. Diseño: Ensayo clínico. Institución: Instituto de Investigaciones Clínicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Pacientes diabéticos dislipidémicos no hipertensos. Intervenciones: Entre enero y octubre 2006, se formó aleatoriamente dos grupos de investigación de 15 pacientes diabéticos dislipidémicos no hipertensos, de diagnóstico reciente, sin tratamiento previo y sin complicaciones crónicas; un grupo recibió simvastatina 40 mg/día y el otro grupo maíz morado (comprimidos deshidratados y micropulverizados 1g/día), por un período de 30 días. Los pacientes paralelamente realizaron dieta hipograsa con evaluación nutricional semanal y recibieron el tratamiento hipoglicemiante convencional con glibenclamida. Se realizó dosaje basal y postratamiento de lípidos séricos, glucosa basal, hemoglobina glicosilada, pruebas de función hepática y renal. El análisis estadístico se efectuó con la prueba t de student, con un intervalo de confianza de 95 por ciento. Principales medidas de resultados: Modificación de los valores séricos de colesterol, triglicéridos y glucosa. Resultados: Se observó que en ambos grupos se produjo reducción en los valores séricos de colesterol total, colesterol LDL, triglicéridos y glucosa en ayunas; asimismo, aumento de los niveles séricos de colesterol HDL. Al compararse los resultados basales y postratamiento para maíz morado, se encontró reducción significativa de los valores de triglicéridos y aumento significativo del colesterol HDL. Para el grupo tratado con simvastatina, hubo reducción estadísticamente significativa del colesterol total, colesterol LDL, triglicéridos y aumento estadísticamente significativo del colesterol HDL, en comparación con los valores basales. El maíz morado mostró optimizar el control de la glucosa, efecto muy superior y estadísticamente significativo en comparación con la simvastatina. Se encontró diferencia estadísticamente significativa para los valores postratamiento de colesterol total, colesterol LDL, colesterol HDL y triglicéridos a favor del grupo que recibió simvastatina en comparación con el que recibió maíz morado. Conclusiones: A la dosis estudiada, el maíz morado mostró ser eficaz para reducir los niveles de triglicéridos, aumentar el colesterol HDL y optimizar el control de la glucosa en pacientes diabéticos no hipertensos. Simvastatina fue más eficaz que el maíz morado en el tratamiento de la dislipidemia, sin efectos importantes sobre la glicemia.

Objectives: To determine the effectiveness of Peruvian purple corn (Zea mays) administration in serum lipids levels reduction (hypolipidemic effect) in non hypertensive diabetic patients with dyslipidemia; to compare hypolipidemic effect of Peruvian purple corn and simvastatin. Design: Clinical essay. Setting: Instituto de Investigaciones Clinicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru. Participants: Non hypertensive dyslipidemic diabetic patients. Interventions: Between January and October 2006 two groups of 15 non hypertensive dyslipidemic diabetic patients were randomly formed, patients with recent diagnosis, without previous treatment and without chronic complications; one group recieved simvastatin 40 mg/day and the other group Peruvian purple corn (dehydrated and micropulverized pills 1g/day) for 30 days. Patients had low fat diet with weekly nutritional evaluation and received conventional hypoglicemic treatment with glibenclamide. Serum lipids, glucose, glycosylated hemoglobin, hepatic and renal function tests were done before and after treatment. Statistical analysis used Student t test with 95 per cent confidence interval. Main outcome measures: Serum cholesterol, triglycerids and glucose levels variation. Results: There was reduction in both groups of total cholesterol, LDL cholesterol, triglycerides and fasting glucose serum levels; HDL cholesterol serum levels increased. Comparing basal and post treatment results for purple corn, there was significant reduction of triglycerides levels and significant increase of HDL cholesterol. In the simvastatin group there was significant statistical reduction of total cholesterol, LDL cholesterol, triglycerides and statistically significant increase in HDL cholesterol compared with basal levels. Compared with simvastatin purple corn optimized glucose control more significantly. There was significant statistical difference for post treatment values of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides in favor of the group that received simvastatin compared with purple corn. Conclusions: At doses studied Peruvian purple corn was effective in reducing triglyceride levels, increasing HDL cholesterol and optimizing glucose control in non hypertensive diabetic patients. Simvastatin was more efficacious than Peruvian purple corn in treatment of dyslipidemia without important effects on glycemia.

Evaluación inmunopatológica del pénfigo foliáceo endémico luego de seis meses de tratamiento: seguimiento de cinco casos de la Amazonía peruana / Evaluation of the immunopathologic response in patiens with endemic pemphigus foliaceus after six months of systemic corticosteroid therapy

Objetivo. Describir la respuesta inmunopatológica de cinco pacientes peruanos con pénfigo foliáceo endémico antes y seis meses después de la terapia con corticosteroides sistémicos. Material y métodos. Estudio descriptivo de tipo serie de casos. Los pacientes fueron sometidos a examen físico, se obtuvodatos cínicos y, luego, una muestra de sangre, a la que se le realizó inmunofluorescencia indirecta (IFI). Se usó como sustratos esófago de mono y piel humana normal, Elisa IgM antidesmogleína 1, Elisa IgG antidesmogleína 1 (total y subclases), inmunoprecipitación (IP) antidesmogleína 1 y antidesmogleína 3. Los pacientes recibieron tratamiento con corticosteroides sistémicos por seis meses obteniéndose nuevamente una muestra de sangre para estudiar su evolución inmunopatológica. Resultados. Al examen físico inicial tres pacientes presentaban la forma clínica generalizada y dos, la localizada; a los seis meses de tratamiento solo un paciente presentaba lesiones activas debido a que su tratamiento había sido irregular. La IgManti-DSG-1 no mostró variaciones importantes manteniéndose positiva en un paciente y haciéndose positiva en un paciente inicialmente negativo. El Elisa para anticuerpos IgG4 se redujo notablemente en todos los pacientes incluidos los que tenían tratamiento irregular. De los dos pacientes que presentaban anticuerpos anti-DSG-3 (Elisa) uno redujo sus valores índices y elotro se hizo negativo; mientras que un paciente inicialmente negativo desarrolló al final del tratamiento anti-DSG-3. Conclusión. La respuesta antidesmogleína 1 IgG total e IgG4 así como la respuesta antidesmogleína 3 muestran reducción de sus valores índices con tendencia a la negativización luego de seis meses de tratamiento lo cual es evidenciado también con la IFI. La respuesta IgM antidesmogleína 1 no mostró variaciones importantes a pesar del tratamiento.

Aim. To describe the immunopathologic response in five patients with endemic pemphigus foliaceus (EPF) before and after six months of therapy with systemic corticosteroids. Material and methods. Case series study. Each patient was examined by a dermatologist who gathered the clinical information. A serum sample was obtained for indirect immunofluorescence (IFI) with monkey esophagous (ME) and normal human skin (NHS) assubstrates. Also, Elisa for IgM and IgG (total and subclasses) antidesmoglein 1 antibodies and immunoprecipitation (IP) for antidesmoglein 1 and 3 were carried out. All the patients received treatment with systemic corticosteroids for six months and blood serum was drawn after wards to assess the immunopathologicresponse. Results. On physical exam, 3 patients had the generalized form ofEPF, 2 patients had the localized form and one patient had someactive lesions because he was not compliant with the therapy.Anti-IgM desmoglein 1 values were decreased in 4 patients buta couple of the values remained unchanged or even increased because they were not completely compliant with the treatment.IgG4 desmoglein 1 antibodies were notably decreased in all the patients. A couple of patients who had antibodies against desmoglein 3 decreased, being one of them negative. One of the patients was initially negative for antibodies against desmoglein3 but later on, he developed anti desmoglein 3 antibodies.Conclusion. The immunological response against IgG and IgG4desmoglein 1 as well as against desmoglein 3 were reduced after the treatment and showed a tendency to become negative. This was correlated with IFI values as well. IgM desmoglein antibodies didnot show important variations despite of the corticosteroid treatment.

Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia / Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposure.

Miliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin.

Infección cutánea por citomegalovirus y radicales libres en el mecanismo patogénico del vitíligo generalizado de inicio reciente / Cytomegalovirus skin infection and free radicals in the initial pathogenic mechanism of early onset generalized vitiligo

Objetivo. Determinar el rol de la infección cutánea por citomegalovirus (CMV) y de los niveles elevados de peroxidación lipídica en piel y sangre, en el mecanismo patogénico del vitíligo generalizado de inicio reciente (VGIR). Material y métodos. Estudio analítico de casos y controles. Los pacientes fueron captados en el Servicio de Dermatología del Hospital Nacional Dos de Mayo (Lima, Perú) y seleccionados de acuerdo a criterios de inclusión/exclusión; luego, pasaron a formar parte de los grupos de investigación: Grupo de estudio: 30 pacientes con diagnóstico de VGIR (1 a 12 meses). Grupo control: 30 sujetos sin lesiones en la piel. Se obtuvo muestras de piel de las lesiones del grupo de estudio y piel sana del grupo control, a las que se les realizó reacción en cadena de la polimerasa (PCR) para CMV y estudio anatomopatológico con latinción de hematoxilina-eosina (HE) e inmunoperoxidasa. Se obtuvo muestras de sangre y piel de ambos grupos a las que se les realizó la cuantificación de peroxidación lipídica, mediante el dosaje del malonildialdehído (MDA). Resultados. El 76.6% de los pacientes con VGIR fueron positivos para genoma de CMV en comparación con el 23,3% del grupo control (p < 0,001). En el examen anatomopatológico realizado con las tinciones HE e inmunohistoquímica no se encontraron casos positivos de infección por CMV en ambos grupos. Los niveles de MDA del grupo de estudio fueron significativamente mayores en los pacientes con VGIR en comparación con el grupo control, tanto en piel (p < 0,001) como en sangre (p < 0,001). Conclusiones. Existe asociación entre la infección cutánea por CMV y el daño mediado por radicales libres constituyen mecanismos importantes en el vitíligo generalizado de inicio reciente.

Aim. To demonstrate skin infection by cytomegalovirus (CMV) and increased serum lipoperoxidation levels in patients with early on set generalized vitiligo. Subjects and methods. Case-control study, implemented since march 2004 until December 2005. Patients were divided into two groups: group A, 30 patients with recent diagnostic of vitiligo; group B, 30 controls without skin lesions. Skin samples were obtained from the patients of both groups; which were assessed bypolymerase chain reaction (PCR) for CMV genome, histopathologic test with hematoxilin-eosin stain and immunoperoxidase. Likewise, blood samples were obtained to determinate radical free levels (1ipoperoxidation). Results. Twenty three patients with vitiligo (76,6%) were positive for CMV genome by PCR test, while 7 controls (23,3%) were positive for CMV genome. Likewise a significant statistically difference for CMV infection in patients with vitiligo versus control group (p < 0,001) was found. The histopathology evaluation was negative for both groups. A significant statistically difference between lipoperoxidation levels inpatients with vitiligo and controls (p < 0,001) was found in skin and blood. Conclusions. There is an association between skin infection by CMV and vitiligo in a select group of patients, which have their systemic oxidant state increased in the first year of the disease.

Características ultraestructurales de la piel de pacientes con pénfigo foliáceo y vulgar endémico de la amazonía peruana: reporte preliminar / Ultrastructural aspects of patientsÆs skin with endemic pemphigus foliaceus and endemic pemphigus vulgaris from the peruvian amazonia: preliminary report

OBJETIVO: Describir las características ultraestructurales de la piel de pacientes con pénfigo foliáceo endémico (PFE) y vulgar endémico (PVE) de la amazonía peruana. INSTITUCIONES: Instituto de Investigaciones Clínicas e Instituto de Patología de la Universidad Nacional Mayor de San Marcos. MATERIAL Y MÉTODOS: Estudio descriptivo de tipo serie de casos. La población estuvo constituida por pacientes con las formas clínicas endémicas de pénfigo foliáceo y pénfigo vulgar captados en Hospital Regional de Pucallpa (Ucayali), Hospital Amazónico de Yarinacocha (Ucayali) y en el HospitalNacional Dos de Mayo (Lima). Se tomó una muestra de piel de los pacientes obteniéndose una fracción para microscopía óptica de alta resolución (MOAR) y otra para microscopía electrónica de transmisión (MET) con la finalidad de determinar características ultraestructurales con énfasis en los desmosomas. RESULTADOS: La MOAR mostró la presencia de acantolisis subcorneal en los 7 casos de PFE y acantolisis suprabasal en los 2 pacientes con PVE. La MET realizada en el PFE mostró separación de las células en el estrato córneo en el 57.1%, separación de las células del estrato espinoso en 28.6% y del estrato basal en el 71.4%. La MET de los pacientes con PVE mostró separación de las células del estrato basal y del estrato espinoso en el 100%. Las alteraciones ultraestructurales observadas en común para el PFE y PVE fueron principalmente la pérdida de la estructura desmosómica, pérdida de la distribución normal de los tonofilamentos y ampliación de los espacios intercelulares. CONCLUSIONES: Los resultados preliminares muestran que las características ultraestructurales del PFE y PVE no presentan diferencias significativas con sus respectivas formas no endémicas. El PFE y PVE no presentan diferencias ultraestructurales importantes salvo la localización primaria de laacantolisis.

OBJETIVE: Describe ultraestructural characteristics of the patientsÆs skin with endemic pemphigus foliaceus (EPF) and endemic pemphigus vulgaris (EPV) from the peruvian amazonia. MATERIAL AND METHODS: Descriptive, prospective and observational study. Population was patients with endemic forms of pemphigus foliaceus and vulgaris from the Regional Hospital of Pucallpa (Ucayali), Hospital Amazonico (Ucayali) and NationalHospital Dos de Mayo (Lima). Skin sampleswas obtained of the patients for a fraction for high resolution light microscopy (HRLM) and other for transmission electronic microscopy (TEM) to determinate the ultrastructural aspects, principally desmosoms. RESULTS: HRLM showed presence of subcorneal acantolisis in the 7 cases of EPF and suprabasalacantolisis in the 2 EPV patients. TEM done in EPF showed separation of cells in the corneal stratum in 57.1%, cells separation of the stratum spinosum in 28.6% and the basal strata in 71.4%. TEM in EPV patients showed cells separation in basal stratum and the stratum espinosum in 100%. Ultraestructural changes observed in both EPF and EPV were lost of desmosomic structure, loss of normal distribution of tonofilaments, enlarge of intercellular spaces. CONCLUSIONS: There are no important differences between ultraestructural characteristic of EPF and EPV with their respective non endemic presentation; except the primary location of the acontolisis.

Cutaneous manifestations of internal malignancies in a tertiary health care hospital of a developing country / Manifestações cutâneas de doenças malignas em um hospital terciário de um país em desenvolvimento

In a public hospital in Lima, Peru, 24 patients with 16 types of paraneoplastic dermatoses were identified by data collection. The most frequent dermatosis was dermatomyositis (four patients). The other dermatoses were malignant acanthosis nigricans, palmoplantar keratoderma, bullous dermatoses, lymphomatoid papulosis, edematous scarring vasculitic panniculitis, Norwegian scabies, primary systemic amyloidosis, necrolytic migratory erythema, infective dermatitis, pancreatic panniculitis, generalized pruritus, Lesser-Trelat syndrome, and acquired ichthyosis. Most of these paraneoplastic dermatoses were diagnosed before (45.8 percent) or at the time of (38.5 percent) the diagnosis of the underlying malignancy. The most frequent underlying malignancies were lymphoma, adenocarcinomas of the upper digestive tract, and malignant neoplasms of the pancreas. The average age of the patients was 47.0 ± 16.9 years and the length of the disease since diagnosis was 13.7 months. The mortality rate was 75 percent. Paraneoplastic dermatoses are rare dermatologic entities that are difficult to diagnose. Surveillance is also hampered when patients do not have easy access to health care centers due to financial and geographical issues. However, when identified, they might facilitate the early diagnosis of an associated tumor and contribute to increase the surveillance of patients.

Em um hospital público em Lima, Peru, 24 pacientes com 16 tipos de dermatoses paraneoplásicas foram identificados por meio de coleta de dados. A dermatose mais frequente foi dermatomiosite (quatro pacientes). As outras dermatoses foram acantose maligna, queratodermia palmoplantar, dermatoses bolhosas, papulose linfomatóide, cicatriz edematosa, paniculite e vasculite, escabiose norueguesa, amiloidose sistêmica primária, eritema necrolítico migratório, dermatite infecciosa, paniculite pancreática, prurido generalizado, sinal de Leser-Trelat e ictiose adquirida. Grande parte dessas dermatoses foi diagnosticada antes (45,8 por cento) ou no momento (38,5 por cento) do diagnóstico do tumor subjacente. Os tumores malignos mais frequentes foram linfoma, adenocarcinomas do trato digestivo superior e neoplasias malignas do pâncreas. A idade média dos pacientes foi de 47.0 ± 16.9 anos e a duração da doença desde o diagnóstico foi de 13,7 meses. A taxa de mortalidade foi de 75 por cento. Dermatoses paraneoplásicas são condições dermatológicas raras de difícil diagnóstico. O controle também é prejudicado quando pacientes não têm acesso fácil à centros de saúde por questões financeiras ou geográficas. No entanto, quando identificadas, elas podem facilitar o diagnóstico precoce de um tumor associado e contribuir para um aumento do controle dos pacientes.

Cryptococcus gattii meningoencephalitis in an HIV-negative patient from the Peruvian Andes / Meningoencefalite causada por Cryptococcus gattii em um paciente HIV-negativo procedente dos Andes Peruanos

We report a case of an immunocompetent Peruvian patient from the Andes with a one-month history of meningoencephalitis. Cryptococcus gattii was identified from a cerebrospinal fluid culture through assimilation of D-proline and D-tryptophan as the single nitrogen source. Initially, the patient received intravenous antifungal therapy with amphotericin B. The patient was discharged 29 days after hospitalization and continued with oral fluconazole treatment for ten weeks. During this period, the patient showed clinical improvement with slight right-side residual weakness. Through this case report, we confirm the existence of this microorganism as an infectious agent in Peru.

Nós reportamos o caso de um paciente peruano immunocompetente proveniente dos Andes com história de um mês com meningoencefalite. Foi identificado o Cryptococcus gattii na cultura de liquido cerebrospinal através da assimilação de D-prolina e D-tryptofano como fonte única de nitrogênio. Inicialmente, o paciente recebeu tratamento antifúngico intravenoso com amfotericina B. O paciente foi liberado 29 dias depois da hospitalização, seguindo tratamento oral durante 10 semanas com fluconazol. Durante este período, o paciente apresentou melhoria clinica e uma leve fraqueza residual direita. Com o reporte do caso, nós confirmamos a existência desse microorganismo como agente infeccioso em nosso país.

Influence of climatic factors on the medical attentions of dermatologic diseases in a hospital of Lima, Peru / Influência de fatores climáticos no tratamento médico de doenças dermatológicas em um hospital em Lima, Peru

BACKGROUND: Significant associations have been described between climatic factors and human health, which can occur in dermatologic diseases too. OBJECTIVE: To determine the influence of the climatic factors on the medical attentions of dermatologic diseases in a general hospital in Lima (Peru). PATIENTS AND METHODS: Observational study which was carried out in a national hospital between January 2004 and December 2007. The diagnoses were classified according to the ICD-10 system. The climate information was provided by the National Oceanographic and Atmospheric Administration from USA(NOAA). RESULTS: 3 294 patients were included in the study, the average age was 35.4 ± 20.7 years old, and 53.2 percent were females. The "El Niño" phenomenon was associated with an increase in the prevalence of actinic keratosis (p=0.002), viral warts (p=0.001) and rosacea (p=0.014). The "La Niña" phenomenon was associated with a reduction in viral warts (p=0.026). Spring was associated with an increase of dermatitis (p=0.003), and summer was associated with an increase of benign neoplasms (p=0.049). CONCLUSION: The climatic variations influenced the occurrence of certain dermatologic diseases. The present study may represent an orientation guide to specialists and general practitioners identifying the most common dermatologic diagnoses and thus enabling better preparation to treat these cases in determined seasons of the year.

FUNDAMENTO: Associações significativas entre fatores climáticos e saúde humana têm sido descritas, inclusive na área de Dermatologia. OBJETIVO: Determinar a influência de fatores climáticos no tratamento de doenças dermatológicas em um hospital em Lima (Peru). PACIENTES E MÉTODOS: Estudo observacional realizado em um hospital em Lima entre janeiro de 2004 e dezembro de 2007. Os diagnósticos foram classificados de acordo com o sistema ICD-10. Informações climáticas foram fornecidas pela "National Oceanographic and Atmospheric Administration" (NOAA - USA). RESULTADOS: 3.294 pacientes participaram do estudo. A idade media foi 35.4 ± 20.7 anos e 53,2 por cento eram mulheres. O fenômeno "El Niño" foi associado a um aumento da prevalência de queratose actínica (p=0,002), verrugas virais (p=0,001) e rosácea (p=0,014). O fenômeno "La Niña" foi associado a diminuição das verrugas virais (p=0,026). A primavera foi associada a um aumento de dermatite (p=0,003) e o verão, a um aumento de tumores benignos (p=0,049). CONCLUSÃO: Variações climáticas influenciam o aparecimento de algumas doenças dermatológicas. O presente trabalho pode orientar especialistas e clínicos gerais por meio da identificação dos diagnósticos dermatológicos mais comuns e, consequentemente, prepará-los para tratar doenças sazonais.

Dermatosis paraneoplásicas: importancia de la examinación cutánea para la detección precoz de una neoplasia maligna / Paraneoplastic dermatoses: importance of cutaneous examination for the early detection of malignancy

Se revisaron los registros de neoplasias malignas presentadas durante el periodo 1993-2007 en un hospital general de Lima, con el objetivo de conocer cuáles presentaban una mayor frecuencia dedermatosis paraneoplásicas. Se diagnosticaron un total de 528 cánceres nuevos siendo el de mama el más frecuente. Se diagnosticó 4.5 dermatosis paraneoplásicas por cada 100 cánceres nuevos diagnosticados y se presentaron con mayor frecuencia en los cánceres que comprometían el tejido linfático y los órganos hematopoyeticos (25,9%), seguidos por los órganos genitales femeninos (10%) y órganos digestivos(5,7%). Reconocer las lesiones características de la dermatosis paraneoplásicas facilita la detección precoz de un cáncer oculto cuyas manifestaciones propias, probablemente, aparecerían hasta meses e incluso años después.

It was revised the record of malignant neoplasms during the period 1993-2007 in a general hospital from Lima, with the objective to know which neoplasms presented a major frequency of paraneoplastic dermatoses. A total of 528 new cancers being breast cancer the most frequent. It was diagnosed 4.5 paraneoplastic dermatoses by each 100 new cancers diagnosed and these dermatoses were presented with major frequency in cancers implicating the Malignant neoplasms, stated orpresumed to be primary, of lymphoid, haematopoietic and related tissue (25,9%), following by female genital organs (10%) and digestive organs (5.7%). Recognize the characteristics of paraneoplastic dermatoses facilitate early detection of occult cancer whose self manifestations probably appear until months or even years later.

Enfermedades dermatológicas en un servicio académico asistencial universitario de Lima-Perú, 2004-2007 / Skin diseases in a dermatology academic teaching division of Lima-Peru, 2004-2007

OBJETIVOS: Evaluar la frecuencia de enfermedades dermatológicas en un Servicio de Dermatología Universitario de la ciudad de Lima. PACIENTES Y METODOS: Estudio descriptivo, observacional y retrospectivo, realizado en el Servicio Académico Asistencial de Dermatología de la UNMSM, durante enero del 2004 a diciembre 2007. Los diagnósticos fueron clasificados de acuerdo al CIE-10. RESULTADOS: Se incluyeron un total de 3294 pacientes nuevos, el promedio de edad fue de 35.4 ± 20.7 años, el 53.35% de pacientes fueron mujeres. Por grupo de enfermedad, las dermatosis infecciosas fueron las más comunes (29.3%), seguidas por las dermatitis (17.7%), neoplasias benignas (9.9%) y enfermedades de los anexos de la piel (9.8%). Las principales dermatosis encontradas fueron las verrugas víricas (14.3%), vitíligo (6%), otros tumores benignos de la piel (5.3%) y acné (4.8%). CONCLUSIONES: Las enfermedades infecciosas y las dermatitis fueron los diagnósticos más comunes. Las universidades como centro de formación integral del médico deberían ofrecer servicios académicos asistenciales que le permitan realizar docencia y proyeccióna la comunidad.

OBJECTIVES: To evaluate the frequency ofdermatological diseases at University Department of Dermatology of Lima. PATIENTSAND METHODS: Descriptive, observational and retrospective, performed at the Dermatology Academic Teaching Division of Universidad Nacional Mayor de San Marcos, during January 2004 to December 2007. Diagnoses were classified according to ICD-10. RESULTS: A total of 3294 new patients, the mean age was 35.4 ± 20.7 years, 53.35% of patients were female. For group of disease, infectious dermatoses were more common (29.3%), following by dermatitis(17.7%), benign neoplasms (9.9%) and diseasesof skin appendages (9.8%). The main dermatoses found were viral warts (14.3%), vitiligo (6%), other benign skin tumors (5.3%) and acne(4.8%). CONCLUSIONS: Infectious diseases and dermatitis were the most common diagnoses. The universities as centre of integral formation of physicians must provide academic assistance services that can deliver teaching and outreach to the community.

Eficacia y seguridad de la terapia tópica antioxidante versus placebo en el tratamiento del vitiligo generalizado de reciente inicio / Efficacia and security of topical antioxidant therapy versus placebo in the treatment of vitiligo of recent onset

Objetivo: Determinar la eficacia de la terapia tópica antioxidante en el tratamiento del vitíligo generalizado de inicio reciente. Material y métodos: Ensayo clínico aleatorizado, doble ciego, controlado con placebo. Los pacientes con vitíligo generalizado de inicio reciente fueron distribuidos aleatoriamente en dos grupos. Grupo de estudio: recibió terapia tópica reciente fueron distribuidos aleatoriamente en dos grupos. Grupo de estudio: recibió terapia tópica antioxidante aplicada en las lesiones cada 12 horas por 30 días. Grupo placebo: recibió terapia tópica con una sustancia carente de actividad farmacológica. La terapia tópica antioxidante estuvo compuesta fundamentalmente por pseudocatalasa activada por luz solar, luego de la aplicación se indicó a los pacientes exposición solar diaria por un período de 30 minutos. Al cabo de 10 semanas de tratamiento se evaluó si hubo re pigmentación, y se comparó los niveles pre y pos tratamiento de malonildialdehido (indicador de per oxidación lipídica) en lesiones cutáneas. Resultados: Al término del tratamiento los valores de MDA en lesiones del grupo que recibió terapia tópica antioxidante mostraron un incremento significativo del 24.5 por ciento con respecto a los valores basales (p=0.035); los valores del grupo placebo también mostraron un incremento significativo del 21.6 por ciento en los valores de MDA con respecto a la medición basal (p menor que 0.001). La evolución clínica mostró re pigmentación parcial de la lesiones en 16.6 por ciento de pacientes que recibieron terapia tópica antioxidante y en 6.6 por ciento de pacientes que recibieron placebo para lo cual no existió diferencia significativa (p = 0.206). En ningún paciente de ambos grupos se observó re pigmentación total de las lesiones. Conclusiones: Nuestros hallazgos en la muestra estudiada demuestran que la terapia tópica antioxidante no es eficaz en el tratamiento del vitíligo generalizado de inicio reciente y no reduce el estrés oxidativo.

Objective: To determine the efficacy of topical antioxidant therapy in the treatment of generalized vitiligo of recent onset. Material and methods: Randomized trial, double-blind, controlled with placebo. Patients with generalized vitiligo of recent onset were randomly distributed in two groups. Study group: They received topical antioxidant therapy applied in lesions each 12 hours for 30 days. Placebo group: They received topical therapy with a substance devoid of pharmacological activity. The topical antioxidant therapy was consisted primarily by pseudocatalasa activated by solar light, after the application, daily solar exposure was indicated to patients by a period of 30 minutes. After 10 weeks of treatment, repigmentation was evaluated whether there and pre and and post treatments of malonyldialdheyde (MDA) levels were compared in cutaneous lesion. Results: At the end of the treatment, values of MDA in lesions of group that receives topical antioxidant therapy showed a significant increase of 24.5 per cent with respect of basal values (p = 0.035); values of placebo group also showed a significant increase of 21.6 per cent in values of MDA with respect to basal measure (p minor that 0.001). Clinical evolution showed partial repigmentation of lesion in 16.6 per cent of patients that received topical antioxidant therapy and in 6.6 per cent of patients that received placebo for which there was no significant difference (p = 0.206). In no one patient of both groups we saw total repigmentation of lesion. Conclusions: Our findings in the sample studied showed that topical antioxidant therapy is not efficacy in the treatment of generalized vitiligo of recent onset and do not reduce the oxidative stress in cutaneous lesions.

Gestante con pénfigo foliáceo endémico y producto libre de enfermedad: Caso clínico / Endemic pemphigus foliaceus in a pregnant woman: Report of one case

Endemic pemphigus foliaceus (EPF) in an autoinmune skin disease present in areas of the Amazonia. We report a 36 year-old woman who presented EPF at 17 weeks of pregnancy. At 29 weeks, she started antimicrobial treatment and steroids. At the moment of delivery, the disease was in remission and cutaneous lesions were not seen in the neonate. Indirect immunofluorescence titers of total IgG in the mother and in the neonate were negative. Sixteen months later, IgG titers in the offspring were 1/20 and remained negative in the mother, who was on low doses of oral corticosteroids (Rev Méd Chile 2009; 137: 1205-8).

Prevalencia de Enfermedades Dermatológicas en una comunidad rural de Ucayali, Perú / Prevalence of skin diseases in a rural area of Peruvian Amazonia

Introcudicción: Las enfermedades dermatológicas representan un problema importante de salud en regiones tropicales. OBJETIVOS: Determinar la prevalencia de enfermedades dermatológicas en una comunidad rural de la selva peruana. DISEÑO: Estudio descriptivo ytransversal. LUGAR: Comunidad rural de Pueblo Libre, Distrito de Campo Verde, Coronel Portillo, Ucayali-Perú. PARTICIPANTES: Todos los pobladores de dicha comunidad. INTERVENCIONES: Durante el mes de febrero del 2005 se realizó una encuesta casa por casa, registrándose las características socio-demográficas, el diagnóstico dermatológico, sexo y edad en una ficha de recolección de datos. Los diagnósticos se basaron de acuerdo a laclasificación internacional de enfermedades (ICD-10). PRINCIPALES MEDIDAS DE RESULTADOS: Prevalencia de enfermedades dermatológicas. RESULTADOS: Se examinó a un total de 111 personas, la mayoría de la población adulta contaba con educación primaria incompleta (38,7 por ciento), se dedicaba preferentemente a la agricultura (34,2 por ciento) y en su totalidad refirió tener un ingreso mensual menor al mínimo vital. El 61,3 por ciento de la población estuvo afectada por una o más enfermedades dermatológicas y se encontró como único factor independiente de riesgo la agricultura como ocupación (p menor que 0,05; OR.: 6,2, IC95 por ciento: 1,1-35,7). Por grupos de enfermedad, las dermatosis infecciosas y parasitarias fueron las más prevalentes (39,6 por ciento), seguidas por las dermatitis (24.3 por ciento) Por enfermedad, las dermatofitosis o tiñas fueron el diagnóstico de mayor prevalencia (14.4 por ciento), seguidas por el prurito (9,9 por ciento). CONCLUSIONES: Existe una alta prevalencia de enfermedades dermatológicas en la comunidad estudiada siendo las más prevalentes las dermatosis infecciosas. Los resultados del presente estudio serviránpara la capacitación de los médicos generales en el diagnóstico y tratamiento de las dermatosis más comunes debido a la escasez.

Background: Dermatological diseases represent an important health problem in tropical areas. Aim: To determinate the prevalence of dermatological diseases in a rural area of thePeruvian Amazonia. Design: Descriptive and cross-sectional study. Place: Rural community of Pueblo Libre, District of Campo Verde, Coronel Portillo, Ucayali-Perú. Participants: All population of this community. Interventions: During February 2005 it was performed astatistical survey door-to-door, social-demographic characteristics, dermatological diagnoses, sex andage were registered in an instrument ofrecollection of dates. Diagnoses were classified in accordance with the ICD-10 system. Main measures of results: Prevalence of dermatologicaldiseases. Results: 111 persons were examinated, the majority of adult population had incomplete Primary School (38,7 per cent), they dedicate their time principally to the agriculture (34,2 per cent) and all of them said to have a salary less to the minimum vital. 61,3 per cent (CI95 per cent: 52,1-70,5) of the population was affected by one or more dermatological diseases and we find the agriculture as the unique independent factor of risk (p minor that 0,05; OR.: 6,2, CI95 per cent: 1,1-35,7). By groups of diseases, infectious and parasitic dermatoses were the most common (39,6 epr cent), following by dermatitis (24.3 per cent). By disease, the dermatophytosis were the most prevalent diagnosis (14.4 per cent), following by the prurito (9,9 per cent). Conclusions: Infectious dermatological diseases were the most common diagnoses in rural areas of the Peruvian Amazonia, which has similar climatic conditions with other tropical regions worldwide. These findings may assist in the training of general doctors in diagnosis and treatment of the mostcommon dermatoses in tropical areas.

Tiempo de espera y su relación con la satisfacción de los usuarios en la farmacia central de un hospital general de Lima / Waiting time and its relation with the userÆs satisfaction in the central pharmacy of a general hospital in Lima

Para determinar la influencia del tiempo de espera sobre la satisfacción del usuario en la farmacia central del Hospital Nacional Dos de Mayo (HNDM), se realizó un estudio transversal donde se registró los tiempos de espera por cada subproceso de atención (facturación, pago en caja y entrega de medicamentos) mediante la observación directa de los usuarios. Se evaluó el nivel de satisfacción del usuario según una escala Likert. Se incluyó 150 usuarios, 59% fueron mujeres, la edad promedio fue de 41,4 +/- 12,6 años. El promedio de tiempo total de espera fue de 37,1 +/- 14,7 minutos. El tiempo de espera fue significativamente mayor en el subproceso de facturación (p < 0,001); asimismo el tiempo que los usuarios tardaron en hacer colas fue mayor que el tiempo efectivo (30,1 +/- 14.0 frente a 6,3 +/- 4,4; p < 0,001). El 17,3% de los usuarios de la farmacia central del HNDM mostraron algún grado de satisfacción. El tiempo de espera menor a 20 minutos fue un predictor de satisfacción del usuario (OR: 4,6 [1,1-18,3]; p < 0,05) independientemente de los otros factores. En conclusión, el tiempo de espera prolongado principalmente en el subproceso de facturación, condiciona un bajo nivel de satisfacción del usuario en la farmacia central del HNDM.

To determine the influence of waiting time on customer's satisfaction in the central pharmacy of the Hospital Nacional Dos de Mayo (HNDM), we conducted a cross-sectional study which recorded the times of each sub process of care (billing, payment in cash and delivery of drugs) through direct observation of users. We evaluated the level of user's satisfaction using a Likert scale. We included 150 users, 59% were women, and its average age was 41.4 +/- 12.6 years. The average total waiting time was 37.1 +/- 14.7 minutes. The waiting time was significantly higher in the sub billing process (p < 0.001) and also the time that users took long queues was higher than the actual time (30.1 +/- 14.0 versus 6.3 +/- 4.4; p < 0.001). 17.3% of the users of the central pharmacy of HNDM showed some degree of satisfaction. The waiting time that it is less than 20 minutes was a predictor of user satisfaction (OR: 4.6 [1.1-18.3], p < 0.05) regardless of other factors. In conclusion, we can say that the long waiting time principally in the sub billing process, determines a low level of user satisfaction in the central pharmacy of HNDM.