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Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.A doença celíaca (DC) é uma doença sistémica desencadeada pela exposição ao glúten em doentes geneticamente susceptíveis. Manifesta-se maioritariamente por uma enteropatia auto-imune associada a auto-anticorpos e aos haplotipos HLA-DQ2 ou HLA-DQ8. A DC afecta aproximadamente 1% da população mundial admitindose, no entanto, que a maioria dos doentes não esteja diagnosticada. As manifestações clássicas de DC são a diarreia e sintomas de malabsorção, no entanto tanto crianças como adultos podem ser pauci-sintomáticos ou apresentar manifestações extra-intestinais incluindo anemia, osteoporose ou alteração das provas hepáticas. O rastreio de base populacional não está recomendado, devendo o foco ser nos grupos de risco para DC. O diagnóstico de DC é um desafio e assenta em três pilares: testes serológicos, histologia duodenal e testes genéticos. Apresentações particularmente difíceis de manejar são os doentes sero-negativos, doentes sero-positivos sem atrofia vilositária e doentes que iniciam dieta sem glúten antes da marcha diagnóstica. O único tratamento com eficácia comprovada é a dieta sem glúten. Apresentamos uma revisão aprofundada da fisiopatologia e manejo da DC, com particular ênfase nos desafios diagnósticos.

Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30–40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.

Febrile illnesses that are caused by malaria and other infectious diseases are a major cause of morbidity and mortality in sub-Saharan Africa. In malaria endemic countries, malaria is considered as one of the most serious febrile illnesses. Over the last two decades, major investment in malaria control has witnessed a major achievement in decline of malaria burden, however, other causes of febrile illnesses have remained prevalent. The decline in malaria burden poses challenges for the diagnosis of malaria in clinical settings, research and disease surveillance. This review highlights the challenges facing the diagnosis of malarial and nonmalarial fevers under reduced malaria burden from the perspectives of parasite diagnosis and interpretations of the diagnoses of malarial and non-malarial fevers, and the possible approaches to address the challenges for a better understanding of the dynamics of febrile illnesses under reduced malaria burden.

Transthyretin cardiac amyloidosis (ATTR-CA) is a challenging and underdiagnosed cause of heart failure. Advances in cardiac imaging have enabled noninvasive diagnosis of ATTR-CA, causing the recent upsurge in disease awareness and detection. ATTR-CA has been increasingly recognized in patients with degenerative aortic stenosis (AS). With the growing number of elderly patients undergoing aortic valve intervention, the identification of ATTR-CA in this group of patients is of high clinical importance. Timely and correct diagnosis is essential for amyloid-directed therapies, as well as deciding on the AS treatment strategy. This review provides a comprehensive overview of the recent studies investigating coexistence of these two entities. We present the data on the prevalence of ATTR-CA in AS and their prognostic associations. As the diagnosis of ATTR-CA may be challenging, special attention is paid to the diagnostic utility of different imaging modalities, namely, echocardiography, cardiovascular magnetic resonance, nuclear imaging, and distinctive imaging features, in patients with dual pathology. We also present a flowchart summarizing integrated imaging in patients with suspected ATTR-CA.

Objective: To raise awareness of the existence of a rare type of malignant trophoblastic tumor and discuss the diagnostic challenges and management of this lesion in a low resource setting.Case report and intervention: A 35 -year -old G6P3 woman was referred to our facility on account of persistent vaginal bleeding due to a suspected incomplete miscarriage with a cervical mass. Her serum β-HCG was elevated (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial histopathological diagnosis of moderately differentiated squamous cell carcinoma was reviewed to epithelioid trophoblastic tumor resulting in an extra-fascial hysterectomy. A final histopathological diagnosis of hybrid Epithelioid Trophoblastic Tumor and Choriocarcinoma (ETT/CC) was made after external review and immunohistochemistry. She received subsequent chemotherapy.Conclusion: Epithelioid trophoblastic tumor and its hybrids are difficult to diagnose. They may be diagnosed as moderately differentiated squamous cell carcinoma especially in low resource settings where cervical squamous cell carcinoma is relatively more common. A high index of suspicion, a serum β HCG test and close collaborationbetween clinicians and pathologists can help make the diagnosis.Funding: NoneKeywords: Epithelioid trophoblastic tumour, choriocarcinoma, diagnostic challenges, low resource setting