Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Demographic and Clinical Characteristics of Human Immunodeficiency Virus-Infected Patients Receiving Dialysis in Portugal: a Nationwide Multicentre Survey

Background: Data on human immunodeficiency virus (HIV) infected patients receiving dialysis in Portugal is scarce. Methods: This nationwide epidemiological survey retrospectively evaluates HIV-infected patients on chronic dialysis in Portugal between 1997 and 2002. Results: Sixty-six patients were evaluated (mean age: 39.1±1.6 years, 47 men, 35 black African). Sixty-two patients started dialysis and 4 patients who were receiving dialysis had HIV seroconversion. Eighty-five percent of patients were treated in Lisbon. The annual incidence of HIV-infected patients on chronic dialysis was 0.5% in 1997 and 0.9% in 2002. Seventy-eight percent of patients were HIV-1 infected , 13% had hepatitis B and 31% hepatitis C. Sexual contact was the mode of transmission of HIV in 53% of cases. Four patients had biopsy-proved HIV-associated nephropathy. Ninety-five percent of patients were on chronic hemodialysis. Fifty percent of patients had acquired immunodeficiency syndrome. At follow-up, 12 patients died. HIV-infected CKD patient survival after starting dialysis was 80% at 3 years. Conclusion: The incidence of HIV-infected patients on chronic dialysis in Portugal has almost doubled. Widespread use of highly active antiretroviral therapy and the increasing number of black Africans from former overseas Portuguese colonies now living in Portugal are possible reasons for this large increase.

Antemortem diagnosis of human rabies in a veterinarian infected when handling a herbivore in Minas Gerais, Brazil

The Ministry of Health's National Human Rabies Control Program advocates pre-exposure prophylaxis (PEP) for professionals involved with animals that are at risk of contracting rabies. We report an antemortem and postmortem diagnosis of rabies in a veterinarian who became infected when handling herbivores with rabies. The antemortem diagnosis was carried out with a saliva sample and a biopsy of hair follicles using molecular biology techniques, while the postmortem diagnosis used a brain sample and conventional techniques. The veterinarian had collected samples to diagnose rabies in suspect herbivores (bovines and caprines) that were subsequently confirmed to be positive in laboratory tests. After onset of classic rabies symptoms, saliva and hair follicles were collected and used for antemortem diagnostic tests and found to be positive by RT-PCR. Genetic sequencing showed that the infection was caused by variant 3 (Desmodus rotundus), a finding confirmed by tests on the brain sample. It is essential that professionals who are at risk of infection by the rabies virus undergo pre-exposure prophylaxis. This study also confirms that molecular biology techniques were used successfully for antemortem diagnosis and therefore not only allow therapeutic methods to be developed, but also enable the source of infection in human rabies cases to be identified accurately and quickly.

Human ocular sparganosis in southern Brazil

We report the first case of human ocular sparganosis in the state of Santa Catarina, southern Brazil. A young female patient presented with three periocular moveable inflammatory masses in her right eye, during two years. By surgical excisional biopsy, a helminth larval stage was removed and identified as sparganum. Clinical, laboratory and epidemiological data on this parasite are presented.

TINU syndrome – Two Clinical Cases of Tubulo-Interstitial Nephritis and Uveitis

TINU (Tubulo-Interstitial Nephritis and Uveitis)syndrome is a rare disease of unknown aetiology characterised by the association between interstitial nephritis and uveitis. The authors present the cases of two young children whose symptoms began with anorexia and weight loss, associated with renal failure and proteinuria of tubular origin. One child also presented anaemia, glycosuria without hyperglycaemia and microhaematuria. A few months later both developed uveitis. In both cases the renal biopsy showed changes compatible with interstitial nephritis. As interstitial nephritis and uveitis aetiologies were not identified, TINU syndrome was suggested as a possible diagnosis. In both children there was a complete resolution, with one needing systemic steroids and immunosuppressive treatment. TINU syndrome should always be considered in the differential diagnosis of patients with renal and ophthalmologic changes.

Prognostic Factors in Adult Patients with Idiopathic IgA Nephropathy

Introduction. IgA nephropathy is the dominant primary glomerular disease found throughout the majority of the world’s developed countries. Accurately identifying patients who are at risk of progressive disease is challenging. We aimed to characterise clinical and histological features that predict poor prognosis in adults. Patients and Methods. We performed a single-centre retrospective observational study of biopsy-proven IgA nephropathy. The primary outcome was renal survival and death from any cause, and the secondary outcome was proteinuria remission. Results. Data from 49 cases were available for analysis with a median follow-up of 4 years. There were no deaths. Univariable analyses identified acute renal failure, low estimated glomerular filtration rate for ≥3 months (low eGFR), arterial hypertension, baseline proteinuria, glomerular sclerosis >50% and interstitial fibrosis >50% as poor prognostic markers. Low eGFR persisted significant by multivariable model that used only clinical parameters. Multivariable models with histopathologic parameters observed that tubular atrophy/interstitial fibrosis >50% was independently associated with the primary outcome. Proteinuria remission throughout follow-up had no prognostic value in our revision. Conclusions. Two independent predictors of poor renal survival at time of biopsy were found: low eGFR and tubular atrophy/interstitial fibrosis >50%.

ABO-Incompatible Liver Transplantation in Acute Liver Failure: A Single Portuguese Center Study

INTRODUCTION: ABO-incompatible liver transplantation (ABOi LT) is considered to be a rescue option in emergency transplantation. Herein, we have reported our experience with ABOi LT including long-term survival and major complications in these situations. PATIENT AND METHODS: ABOi LT was performed in cases of severe hepatic failure with imminent death. The standard immunosuppression consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Pretransplantation patients with anti-ABO titers above 16 underwent plasmapheresis. If the titer was above 128, intravenous immunoglobulin (IVIG) was added at the end of plasmapheresis. The therapeutic approach was based on the clinical situation, hepatic function, and titer evolution. A rapid increase in titer required five consecutive plasmapheresis sessions followed by administration of IVIG, and at the end of the fifth session, rituximab. RESULTS: From January 2009 to July 2012, 10 patients, including 4 men and 6 women of mean age 47.8 years (range, 29 to 64 years), underwent ABOi LT. At a mean follow-up of 19.6 months (range, 2 days to 39 months), 5 patients are alive including 4 with their original grafts. One patient was retransplanted at 9 months. Major complications were infections, which were responsible for 3 deaths due to multiorgan septic failure (2 during the first month); rejection episodes (4 biopsy-proven of humoral rejections in 3 patients and 1 cellular rejection) and biliary. CONCLUSION: The use of ABOi LT as a life-saving procedure is justifiable in emergencies when no other donor is available. With careful recipient selection close monitoring of hemagglutinins and specific immunosuppression we have obtained acceptable outcomes.

Case for Diagnosis

Blastic plasmacytoid dendritic cell tumor is a rare, highly aggressive systemic neoplasm for which effective therapies have not yet been established. We describe a 73-year-old man with multiple nodules and patches emerging on the trunk and limbs. Lesional skin biopsy revealed a plasmacytoid dendritic cell tumor with dense dermal infiltrate of tumor cells with blastoid features. No apparent systemic involvement was identified in the initial stage. The patient was treated with prednisone daily, with notorious improvement of the skin lesions, although no complete remission was obtained. During the six-month follow-up period, no disease progression was documented, but fatal systemic progression occurred after that period of time.

Obstipação Funcional e Encopresis - Estudo Clínico e Manométrico

A obstipação é um problema frequente na idade pediátrica. Os autores propuseram-se analisar os dados clínicos e os registos da manomatria anorectal de um grupo de crianças com obstipação funcional para encontrar as características preditivas de risco de desenvolvimento de encopresis. Foram analisados os processos de 46 crianças com características clínicas de obstipação funcional e agrupadas em dois grupos. o grupo A (n=20) constítuido por crianças obstipadas mas sem encopresis e o grupo B (n=26) por crinaças com história de encopresis. Todas as crianças efecturam manometria anorectal. A duração da obstipação foi mais prolongada no grupo das crianças encopréticas. A análise dos traçados manométricos não demonstrou diferenças significativas entre os dois grupos, no que diz respeito ao tónus anal mínimo e máximo e à contracção anal voluntária. O reflexo recto anal inibidor (RRAI) esteve presente em todos os doentes, para volumes de distensão elevados, mas semelhantes. O limiar da sensibilidade à distensão foi mais elevado no grupo B. A relação entre os volumes de distensão desencadeando a sensaibilidade rectal e o RRAI foi semelhante nos dois grupos e em 50% dos casos o RRAI precedeu a sensibilidade para a distensão rectal. Os factores preditivos de aparecimento de encopresis, forma o sexo masculino e o tempo de duração da obstipação.

Whipple's disease: rare disorder and late diagnosis

Whipple's disease is a rare systemic infectious disorder caused by the bacterium Tropheryma whipplei. We report the case of a 61-year-old male patient who presented to emergency room complaining of asthenia, arthralgia, anorexia, articular complaints intermittent diarrhea, and a 10-kg weight loss in one year. Laboratory tests showed the following results: Hb = 7.5 g/dL, albumin = 2.5 mg/dL, weight = 50.3 kg (BMI 17.4 kg/m²). Upper gastrointestinal endoscopy revealed areas of focal enanthema in the duodenum. An endoscopic biopsy was suggestive of Whipple's disease. Diagnosis was confirmed based on a positive serum polymerase chain reaction. Treatment was initiated with intravenous ceftriaxone followed by oral trimethoprim-sulfamethoxazole. After one year of treatment, the patient was asymptomatic, with Hb = 13.5 g/dL, serum albumin = 5.3 mg/dL, and weight = 70 kg (BMI 24.2 kg/m²). Whipple's disease should be considered a differential diagnosis in patients with prolonged constitutional and/or gastrointestinal symptoms. Appropriate antibiotic treatment improves the quality of life of patients.

Diabetic Mastopathy: a Case Report

Diabetic mastopathy (DMP) is an uncommon collection of clinical, radiological, and histological features, classically described in premenopausal women with long-term insulin-dependent diabetes mellitus. This entity can mimic breast carcinoma, but, in the appropriate clinical and imaging setting, the diagnosis can be made by core biopsy, avoiding unnecessary surgeries. We report the case of a 34-year-old female, with a 12-year history of type 1 diabetes, who presented with bilateral breast lumps. Mammography, ultrasonography, and magnetic resonance imaging could not exclude the suspicion of malignancy, and a core biopsy was performed showing the typical histologic features of DMP. The literature is briefly reviewed.

Argyria. Case Report

A 70-year-old male rural worker was referred to our clinic with widespread grey pigmentation of the skin and nails. The condition had been asymptomatic for its entire duration (5 years). He reported past intranasal application of 10% Silver Vitellinate. A skin biopsy was performed and histology corroborated the clinical diagnosis of Argyria. This case represents a currently rare dermatological curiosity. Although silver colloids and salts have been withdrawn and/or banned by some drug surveillance agencies, they continue to be freely sold and unregulated as food supplements and as ingredients in alternative medicines, thereby risking the emergence of new cases of silver poisoning.

Case for Diagnosis

A 27 year-old-man, with no known personal or familial history of disease, mentioned a 10-year history of asymptomatic groups of telangiectasias, with a Blaschko lines distribution on the right lateral aspect of the neck and asymptomatic. He denied any episodes of disease or drug intake that could be associated with the disease. Blood work had no changes, namely of liver enzymes or infectious serologies. The clinical diagnosis of Idiopathic Acquired Unilateral Nevoid Telangiectasia was made, an uncommon, benign vascular malformation. The patient declined doing a cutaneous biopsy or treatment with a cosmetic intent.

CASE STUDY OF A PATIENT WITH HIV-AIDS AND VISCERAL LEISHMANIASIS CO-INFECTION IN MULTIPLE EPISODES

SUMMARYReport of a 45-year-old male farmer, a resident in the forest zone of Pernambuco, who was diagnosed with human immunodeficiency virus (HIV) in 1999 and treated using antiretroviral (ARV) drugs. In 2005, the first episode of visceral leishmaniasis (VL), as assessed by parasitological diagnosis of bone marrow aspirate, was recorded. When admitted to the hospital, the patient presented fever, hepatosplenomegaly, weight loss, and diarrhea. Since then, six additional episodes of VL occurred, with a frequency rate of one per year (2005-2012, except in 2008). In 2011, the patient presented a disseminated skin lesion caused by the amastigotes of Leishmania, as identified by histopathological assessment of skin biopsy samples. In 2005, he was treated with N-methyl-glucamine-antimony and amphotericin B deoxycholate. However, since 2006 because of a reported toxicity, the drug of choice was liposomal amphotericin B. As recommended by the Ministry of Health, this report emphasizes the need for HIV patients living in VL endemic areas to include this parasitosis in their follow-up protocol, particularly after the first infection of VL.

Iatrogenia rara ao alopurinol

Existem raríssimos casos citados de granulomas da medula óssea por iatrogenia ao alopurinol. Os granulomas são um achado raro nas biópsias da medula óssea e podem ter várias etiologias, nomeadamente infeciosas, neoplásicas, autoimunes, iatrogénicas ou sarcoidose. Na ausência de características patognomónicas, recorre-se à integração de dados clínicos, laboratoriais, imagiológicos e histológicos para estabelecer o diagnóstico. Descrevemos o caso de um caucasiano, 59 anos, referenciado à consulta de Medicina por gota úrica, tendo sido medicado com alopurinol e colchicina. Ao longo do seguimento surgiram anemia e trombocitopenia. Do estudo por mielograma e biópsia osteomedular salientavam-se “numerosos granulomas de tipo epitelióide, sem células multinucleadas, sem identifica- ção de microrganismos PAS pós diástase ou Ziehl-Neelsen, sem neoplasia, compatível com mielite granulomatosa”. A etiologia estabelecida foi a de reação de hipersensibilidade ao alopurinol pelo que foi descontinuado. Repetido o exame um ano depois, não se observaram granulomas, facto que reforçou a hipótese diagnóstica.