Progressive multifocal leukoencephalopathy: a challenging diagnosis established at autopsy.

Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.

Progressive multifocal leukoencephalopathy: a challenging diagnosis established at autopsy

Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.

Celiac Crisis: an unusual presentation of gluten-sensitive enteropathy

Celiac disease (CD)­also known as gluten-sensitive enteropathy­is a chronic, genetically predisposing and autoimmune entity with a wide range of clinical manifestations triggered by gluten ingestion, which affects 1% of the general population. Currently, up to 60% of the diagnosis of CD is in adults due to the atypical course of the disease. The severe acute onset of CD­also called celiac crisis­is very uncommon and is still not well documented in adults. We report the case of a 58-year-old man who presented a 45-day history of subtle-onset diarrhea followed by malabsorption syndrome with progressive weight loss, anasarca, and electrolyte disturbances. The diagnostic work-up included an upper digestive endoscopy, which showed scalloping of the duodenal mucosa with pathological features confirmed on biopsies. Specific antibodies were positive, and a satisfactory clinical response was obtained once a gluten-free diet was started. Celiac crisis is a rare initial presentation of CD characterized by severe diarrhea, dehydration, weight loss, hypoproteinemia, and metabolic and electrolyte disturbances. Although rare, it should be considered in patients with apparently unexplained chronic diarrhea.

Celiac Crisis: an unusual presentation of gluten-sensitive enteropathy.

Celiac disease (CD)-also known as gluten-sensitive enteropathy-is a chronic, genetically predisposing and autoimmune entity with a wide range of clinical manifestations triggered by gluten ingestion, which affects 1% of the general population. Currently, up to 60% of the diagnosis of CD is in adults due to the atypical course of the disease. The severe acute onset of CD-also called celiac crisis-is very uncommon and is still not well documented in adults. We report the case of a 58-year-old man who presented a 45-day history of subtle-onset diarrhea followed by malabsorption syndrome with progressive weight loss, anasarca, and electrolyte disturbances. The diagnostic work-up included an upper digestive endoscopy, which showed scalloping of the duodenal mucosa with pathological features confirmed on biopsies. Specific antibodies were positive, and a satisfactory clinical response was obtained once a gluten-free diet was started. Celiac crisis is a rare initial presentation of CD characterized by severe diarrhea, dehydration, weight loss, hypoproteinemia, and metabolic and electrolyte disturbances. Although rare, it should be considered in patients with apparently unexplained chronic diarrhea.

Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring cell gastric adenocarcinoma.

Gastric adenocarcinoma is a common neoplasia and is responsible for up to 30% of the overall deaths due to cancer. Advanced disease is mostly characterized by peritoneum, liver, and lung involvement. The spread of the disease to the bone is rare, and bone marrow dissemination is even rarer. In this setting, leukoerythroblastosis may be the initial manifestation of the disease. The authors report the case of a 64-year-old Caucasian man who sought medical care complaining of back pain, weakness, and weight loss. The physical examination revealed pallor, and the laboratory work-up depicted severe anemia and thrombocytopenia; the peripheral blood smear was consistent with leukoerythroblastosis. The ongoing investigation through a bone marrow biopsy showed massive involvement of the bone marrow by a signet ring cell adenocarcinoma. During hospitalization, the patient presented melena, and an upper digestive endoscopy depicted an ulcerated and infiltrative lesion in the cardia, upon which the histological examination revealed a signet ring cell adenocarcinoma. This case highlights the bone marrow invasion represented by bicytopenia and leukoerythroblastosis as the initial manifestation of this histological type of gastric cancer. Although treatment attempts were made with chemotherapy and radiotherapy, the patient died early on, showing the aggressive behavior of this form of tumoral presentation.

Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring cell gastric adenocarcinoma

Gastric adenocarcinoma is a common neoplasia and is responsible for up to 30% of the overall deaths due to cancer. Advanced disease is mostly characterized by peritoneum, liver, and lung involvement. The spread of the disease to the bone is rare, and bone marrow dissemination is even rarer. In this setting, leukoerythroblastosis may be the initial manifestation of the disease. The authors report the case of a 64-year-old Caucasian man who sought medical care complaining of back pain, weakness, and weight loss. The physical examination revealed pallor, and the laboratory work-up depicted severe anemia and thrombocytopenia; the peripheral blood smear was consistent with leukoerythroblastosis. The ongoing investigation through a bone marrow biopsy showed massive involvement of the bone marrow by a signet ring cell adenocarcinoma. During hospitalization, the patient presented melena, and an upper digestive endoscopy depicted an ulcerated and infiltrative lesion in the cardia, upon which the histological examination revealed a signet ring cell adenocarcinoma. This case highlights the bone marrow invasion represented by bicytopenia and leukoerythroblastosis as the initial manifestation of this histological type of gastric cancer. Although treatment attempts were made with chemotherapy and radiotherapy, the patient died early on, showing the aggressive behavior of this form of tumoral presentation.

Amyloidosis: an unusual cause of portal hypertension.

Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis.

Severe cognitive dysfunction and shrinking lung syndrome in systemic lupus erythematous.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ or system. Neuropsychiatric and pulmonary involvement can occur in 40 and 50% of patients respectively, and may occur in several different clinical forms. While the main neuropsychiatric manifestations are represented by cognitive impairment, organic cerebral syndromes, delirium, psychosis, seizures, and peripheral neuropathies, the main forms of pulmonary involvement are pleurisy with or without pleural effusion, pneumonitis, interstitial disease, pulmonary hypertension, and alveolar hemorrhage. The authors report the case of a 49-year-old woman whose first manifestation of SLE was represented by two rare manifestations: rapidly progressive cognitive impairment, which was associated with respiratory failure caused by the shrinking lung syndrome. The authors call attention to the under-diagnosis of lupus pulmonary complications and its association with severe cognitive impairment that often necessitates aggressive treatment.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) syndrome and pulmonary thromboembolism: an overlooked concomitance.

The Eosinophilic Granulomatosis with Polyangiitis (formerly Churg- Strauss Syndrome) (EGPA) is a systemic inflammatory disease characterized by the presence of rhinitis, asthma, peripheral eosinophilia, and vasculitis-the latter being characteristic of the late stage of the disease. After several years from the onset of the disease, small- and medium-sized vessel vasculitis ensues, undertaking various organs and systems. Upper and lower airways, skin, nervous system, gastrointestinal tract, heart, and kidneys are the most commonly involved organs. It is believed that tissue injury is the result of processes mediated by antineutrophil cytoplasmic antibody (ANCA), or toxic mediators released by eosinophils. Although it is classified as ANCA-associated vasculitis, these autoantibodies are present in only 40% of cases. The authors report the case of a patient with EGPA, who had a history of asthma, peripheral and central neuropathy, palpable purpura, gastrointestinal micro perforation, peripheral eosinophilia, and the presence of myeloperoxidase-antineutrophil cytoplasmic antibody. Inflammatory parameters improved after the initiation of treatment, but 1 month after hospital discharge the patient developed symptoms compatible with pulmonary embolism and died. Thrombophilia that occurs in EGPA is due to the interaction between the inflammatory response and eosinophilia with the clotting system resulting in a pro-thrombotic state. Although not yet well-determined, the authors call attention to the possibility of the impact of thromboembolic events on the prognosis of patients with EGPA. In addition to the adequate immunosuppressive treatment, prophylaxis and treatment for thrombosis should never be overlooked.

Black esophagus: exploring the dark.

Black esophagus is a rare but underdiagnosed disease. It occurs most frequently in severely ill patients and carries a high mortality rate. Cause of death is usually attributed to the comorbid conditions. Treatment is directed at the underlying cause, acid suppression and keeping the patient nil-per-os. Surgery is needed in complicated cases and stenosis is the most feared longterm sequel. In the present article, two cases are described and literature is reviewed.

Paroxysmal nocturnal hemoglobinuria: rare cause of acute renal failure.

Paroxysmal nocturnal hemoglobinuria is a rare acquired disease, characterized by hemolytic anemia, recurrent infections, cytopenias, and vascular thrombosis. It occurs by non-malignant clonal expansion of one or more hematopoietic stem cells that acquired somatic mutations in PIG-A gene linked to chromosome X. This mutation results in lower erythrocyte expression of CD55 and CD59 surface proteins and consequently increased susceptibility to the complement system. The renal involvement is generally benign, resulting in mild impairment in urinary concentration. Acute renal failure requiring hemodialytic support accompanying PNH is rarely observed. The authors report a case of a 37-year-old male who presented with bicytopenia (hemolytic anemia and thrombocytopenia) associated with acute renal failure requiring dialysis. Diagnosis was challenging because of the rarity and unfamiliarity with this entity, but was confirmed by flow cytometry. In the course of the disease, acute pyelonephritis with multiple renal abscesses was diagnosed requiring prolonged antibiotic therapy. Patient outcome was favorable after the control of hemolysis and the infection treatment.

Infective endocarditis: a consumptive disease among the elderly.

The clinical presentation of infective endocarditis varies according to the etiologic agent and the host. In elderly individuals, infective endocarditis can be difficult to diagnose and poses a challenge for the physician. The course of subacute infective endocarditis is indolent, and the onset of cardiac structural lesion is slow and gradual. In elderly patients, anemia and weight loss are occasionally the only or the most striking symptoms. In such cases, the clinical reasoning process leads to a hypothesis of wasting syndrome or neoplastic disease, especially when there is no fever. We report the case of an elderly patient who had mitral insufficiency due to degenerative valve disease and presented with bacterial endocarditis due to Streptococcus mitis. The patient was not treated, because the diagnosis was not established in a timely manner. It is of note that the patient presented with marked weight loss and no fever. The autopsy revealed impairment of the mitral valve and left atrium due to endocarditis, as well as lung involvement due to chronic inhalation of smoke from biomass burning, such as that produced by wood-burning stoves.

Comprometimento do sistema nervoso no lupus eritematoso sistemico / Involvement of the nervous system in systemic lupus erythematosus

O comprometimento do sistema nervoso (SN) no lupus eritematoso sistemico (LES) envolve multiplas manifestacoes de graus variaveis, entre elas fadiga, perda de capacidade de concentracao, convulsoes e coma. O diagnostico precoce do envolvimento do SN e de fundamental importancia para a adocao de medidas terapeuticas mais objetivas. No presente trabalho os autores discorrem sobre aspectos clinicos, laboratoriais e terapeuticos do comprometimento do SN no LES.

Miosite tropical / Tropical myositis

Os autores descrevem seis casos de miosite tropical ou piomiosite que ocorreram na Divisao de Clinica Medica do Hospital Universitario da USP durante o periodo de 1985 a 1992. O Staphylococcus aureus foi o agente responsavel por este quadro infeccioso sendo isolado a partir de abscessos musculares em quatro casos e de hemoculturas em dois casos. A antibioticoterapia adequada associada a drenagem cirurgica determinou evolucao satisfatoria, sem mortalidade e sequelas osteomusculares.

Indice de estadiamento radiologico na osteoartrose / Radiological staging index in osteoarthrosis

A associacao de dor articular e alteracoes radiologicas (como osteofitos, reducao do espaco articular e em alguns casos cistos e erosoes osseas) e o criterio mais comumente adotado na pratica diaria para o diagnostico de osteoartrose (OA). No entanto, o achado de tais alteracoes radiologicas nao permite quantificar de maneira objetiva a intensidade do comprometimento articular. Com o objetivo de mensurar de forma quantitativa as lesoes radiologicas que ocorrem na OA, os autores elaboram um INDICE DE ESTADIAMENTO RADIOLOGICO (IER), que leva em consideracao os seguintes parametros: I. gravidade das alteracoes radiologicas; II. area da articulacao comprometida e III. numero de articulacoes afetadas (uma ou mais de acordo com o interesse do investigador). A aplicacao deste indice na pratica medica, permite obter de forma simples a quantificacao das lesoes radiologicas da osteoartrose, possibilitando deste modo uma melhor monitorizacao clinica.

Mini-pulsos de ciclofosfamida no tratamento da dermatopolimiosite com envolvimento pulmonar / Mini-pulses of cyclophosphamide in the treatment of dermatopolymyositis with pulmonary envolvement

Os autores apresentam um novo esquema terapeutico para o tratamento da Dermatopolimiosite (DM/PM) com fibrose pulmonar refrataria a corticoterapia. Com o objetivo de atingir um controle clinico adequado e minimizar a ocorrencia de efeitos adversos, os autores propoem a utilizacao de ciclofosfamida endovenosa em esquema de pequenas doses mensais (mini-pulsos) e descrevem dois pacientes portadores de DM/PM com comprometimento pulmonar que nao respondem a prednisona. Foram submetidos ao esquema de mini-pulsos por aproximadamente dois anos com normalizacao do quadro clinico muscular e pulmonar que se mantiveram ate a ultima avaliacao ambulatorial.

Lupus eritematoso sistemico no idoso: caracteristicas clinicas e laboratoriais / Systemic lupus erythematosus in the elderly: clinical and laboratorial characteristics

As caracteristicas clinicas e laboratoriais de 199 pacientes com lupus eritematoso sistemico (LES) foram estudadas. Os pacientes que apresentaram inicio apos 50 anos foram comparados aqueles com inicio mais precoce. O acometimento clinico definiu diferencas importantes entre as duas populacoes. Os pacientes idosos apresentaram maior frequencia de manifestacoes musculares (p<0,05) e menor frequencia de alteracoes cutaneas (p<0,001) e de alopecia (p<0,02). Alem disso a apresentacao clinica mais frequente foi fraqueza muscular, poliartrite e emagrecimento (>10Kg), condicoes estas que podem sugerir o diagnostico de polimialgia reumatica ou doenca neoplasica. A presenca dos diversos auto-anticorpos foi semelhante nos dois grupos. Em contraste com estudos anteriores nao encontramos maior frequencia de anti-La/SSB no LES de inicio tardio. A apresentacao clinica do LES no idoso e menos exuberante e muitas vezes pouco caracteristica, exigindo consideracao especial para este diagnostico no sentido de se evitar retardo na sua terapeutica.