Atypical Manifestations Of Disease Research Articles

Atypical Manifestations of Syphilis: A 10-Year Retrospective Study.

Background: The incidence of syphilis has increased in high-income countries in the past few decades, especially among men who have sex with men. In the present study, we aimed to analyze the correlations between atypical syphilis manifestations and the demographic, clinical, and laboratory features of patients and to review unusual presentations of syphilis reported in the literature. Methods: We conducted a retrospective analysis of 307 patients with syphilis diagnosed between 1 January 2013 and 31 October 2023 at the sexually transmitted infection (STI) centers of the University of Genoa and University of Foggia with both typical and atypical manifestations of disease. Results: In our series, atypical manifestations were detected in 25.8% of the patients, especially in the secondary stage of the disease. Lesions with annular morphology and lesions presenting as itchy erythematous scaly plaques with a psoriasiform appearance were the most common atypical presentations of secondary syphilis. A statistical analysis revealed that homosexual orientation, syphilis reinfection, and venereal disease research laboratory (VDRL) titers > 1:32 were correlated with atypical manifestations. Conclusions: Our study demonstrates that the spectrum of syphilis manifestations, in all the stages of the disease, is wide; atypical manifestations often pose diagnostic challenges, may delay the provision of appropriate treatment, and facilitate the spread of the infection.

Pitfalls and pearls in diagnosing inflammatory arthritis in older patients

Given current demographic shifts, the number of older adults continues to grow, with almost half of patients over 65 being diagnosed with some form of arthritis. Rheumatic diseases pose unique diagnostic challenges in older patients due to the convergence of physiologic changes of aging, confounding difficulties to care, and atypical disease manifestations. This review summarizes the current published evidence to guide clinicians in evaluating geriatric patients with rheumatologic concerns, focusing on inflammatory arthritis. Using the background of epidemiologic data on various musculoskeletal diseases, clinical presentations, current diagnostic tests, and known physiologic changes of aging, this review highlights five diagnostic pitfalls in inflammatory polyarthritis among older patients. The pitfalls include: 1) broader differential diagnosis; 2) atypical presentations; 3) communication, cognitive, and social impairments; 4) the role of chronological vs. biological age; and 5) anchoring bias by assuming older adults are simply “older young adults”. These pitfalls are discussed in the context of geriatric principles such as the “hallmarks of aging” and the expected pathophysiologic changes of organ systems. Furthermore, the review discusses the strengths and weaknesses of diagnostic tests used in arthritis and introduces some of the geriatric assessment tools that systematically evaluate multimorbidity and geriatric syndromes. With familiarity of the potential diagnostic pitfalls, knowledge of both normal and pathologic aging processes, awareness of the difference between biological and chronological age, and the ability to use geriatric assessment tools to better characterize older patients, clinicians will be better able to diagnose and manage rheumatic conditions in this population.

The research progress of Chikungunya fever.

Chikungunya fever, an acute infectious disease caused by Chikungunya virus (CHIKV), is transmitted by Aedes aegypti mosquitoes, with fever, rash, and joint pain as the main features. 1952, the first outbreak of Chikungunya fever was in Tanzania, Africa, and the virus was isolated in 1953. The epidemic has expanded from Africa to South Asia, the Indian Ocean islands and the Americas, and is now present in more than 100 countries and territories worldwide, causing approximately 1 million infections worldwide each year. In addition, fatal cases have been reported, making CHIKV a relevant public health disease. The evolution of the virus, globalization, and climate change may have contributed to the spread of CHIKV. 2005-2006 saw the most severe outbreak on Reunion Island, affecting nearly 35% of the population. Since 2005, cases of Chikungunya fever have spread mainly in tropical and subtropical regions, eventually reaching the Americas through the Caribbean island. Today, CHIKV is widely spread worldwide and is a global public health problem. In addition, the lack of a preventive vaccine and approved antiviral treatment makes CHIKV a major global health threat. In this review, we discuss the current knowledge on the pathogenesis of CHIKV, focusing on the atypical disease manifestations. We also provide an updated review of the current development of CHIKV vaccines. Overall, these aspects represent some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development of CHIKV and potential CHIKV vaccines for current development and clinical trials.

A Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in many parts of the world causing large-scale outbreaks. CHIKV infection presents as a febrile illness known as chikungunya fever (CHIKF). Infection is self-limited and characterized mainly by severe joint pain and myalgia that can last for weeks or months; however, severe disease presentation can also occur in a minor proportion of infections. Among the atypical CHIKV manifestations that have been described, severe arthralgia and neurological complications, such as encephalitis, meningitis, and Guillain–Barré Syndrome, are now reported in many outbreaks. Moreover, death cases were also reported, placing CHIKV as a relevant public health disease. Virus evolution, globalization, and climate change may have contributed to CHIKV spread. In addition to this, the lack of preventive vaccines and approved antiviral treatments is turning CHIKV into a major global health threat. In this review, we discuss the current knowledge about CHIKV pathogenesis, with a focus on atypical disease manifestations, such as persistent arthralgia and neurologic disease presentation. We also bring an up-to-date review of the current CHIKV vaccine development. Altogether, these topics highlight some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development and clinical trials of CHIKV potential vaccine candidates.

Imaging spectrum of abdominal manifestations of COVID-19.

Coronavirus disease 2019 (COVID-19) has posed a serious threat to global public health with its rapid spread, high fatality, and severe burden on health care providers all over the world. Although COVID-19 has been established as a respiratory tract infection, it can manifest with gastrointestinal symptoms as a consequence of direct infection by the virus or due to inflammation-mediated cytotoxicity. It has been observed that COVID-19 patients presenting with gastrointestinal symptoms tend to progress to a severe form of disease with increased morbidity and mortality, thus indicating the need for timely management. COVID-19 manifests with a wide spectrum of radiologic findings on gastrointestinal tract imaging, encompassing bowel abnormalities, hepato-biliary and pancreatic involvement, vascular occlusion, and solid organ infarction. Early recognition of these imaging features can facilitate timely treatment of COVID-19 associated gastrointestinal tract complications and may prompt the diagnosis of COVID-19 in patients with atypical disease manifestations. The aim of this article is to provide an overview of the various gastrointestinal imaging manifestations that can be encountered in patients with COVID-19, with an emphasis on early diagnosis of the disease as well as treatment related complications.

EP05 COVID-19 and the biliary tree: atypical manifestations of disease during the pandemic

Case report - IntroductionCOVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, and first described in Wuhan, China in December 2019, has affected more than 19 million patients worldwide and resulted in more than 700,000 deaths at the time of writing1. Patients with rheumatic diseases and those receiving immunosuppressive treatment are felt to be at greater risk of complications from this illness, though registry and trial data should help refine our understanding of these risks. We hereby describe a case of COVID-19 complicating an unusual rheumatic illness, resulting in severe multi-system disease and premature death.Case report - Case descriptionA 69 year-old male presented to rheumatology and haematology with symmetrical polyarthritis, thrombocytopenia (18 x 109/L), eosinophilia (25.4 x 109/L), raised C-reactive protein (CRP, 43 mg/L), positive rheumatoid factor (>200), antinuclear antibody (ANA) and anti-Ro. Bone marrow biopsy did not demonstrate evidence of haematological malignancy. Seropositive rheumatoid arthritis and connective tissue disease overlap were diagnosed, and treatment with Prednisolone 60mg daily was initiated. Despite rituximab and intravenous immunoglobulins, thrombocytopenia deteriorated on reducing corticosteroids, however the addition of mycophenolate mofetil (MMF) allowed gradual prednisolone tapering to 3mg daily. Hydroxychloroquine was briefly added but discontinued due to headaches. MMF was discontinued after he developed fungal pneumonia followed by jaundice. Liver biopsy was consistent with drug-induced cholestasis, attributed to co-amoxiclav, and his liver function tests (LFTs) improved on ursodeoxycholic acid. Following a further deterioration in thrombocytopenia, hyperferritinaemia and new onset erythema nodosum, he had a repeat bone marrow examination. This demonstrated large areas of fibrosis and granulomatous inflammation with a dense, pleomorphic T-cell infiltrate, but no haemophagocytosis. Haematologists felt this was reactive and prednisolone dose was increased to 10mg daily.Six months later he developed cholangitis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a tight 4cm stricture of the distal common bile duct (CBD) within the head of pancreas, which was diffusely swollen without any clear focal mass. Serum amylase was mildly elevated (316 units/L). Concurrent CT thorax, abdomen and pelvis demonstrated bilateral ground-glass changes within the lungs, and a SARS-CoV-2 nasopharyngeal PCR test was positive, though he had no respiratory symptoms or oxygen requirement at that stage.Sadly, four days after the CT scan and before a planned endoscopic retrograde cholangiopancreatography (ERCP) could be performed, he became markedly hypoxic with plain chest x-ray features suggestive of COVID-19 pneumonia. Despite medical management, including doubling of his prednisolone dose, he rapidly deteriorated and died.Case report - DiscussionThis case highlights an unusual presentation of COVID-19 in a patient with a complex background of inflammatory arthritis with immune-mediated thrombocytopenia. At the time of his final illness, these conditions were managed with steroid monotherapy. Based on the COVID-19 risk matrix recommended by the British Society for Rheumatology, he was not identified as a patient requiring shielding.Cholangitis was the major problem precipitating his final admission to hospital, and at the time of admission he had no respiratory symptoms. One week prior to this admission, his father-in-law had died of COVID-19 pneumonia, though they had not been in recent direct contact. Interstitial lung changes were incidentally noted on a CT performed to identify the cause of cholangitis, which prompted the nasopharyngeal PCR that detected SARS-CoV-2. This occurred prior to widespread routine testing of hospital inpatients for SARS-CoV-2 by PCR. Unfortunately he then rapidly developed COVID-19 pneumonia and died before the underlying cause of cholangitis could be definitively identified, though an MRCP demonstrated an obstructed CBD within a diffusely swollen pancreas, where a differential diagnosis of pancreatic malignancy or autoimmune pancreatitis was suggested by the reporting radiologist. There are emerging case reports of COVID-19 resulting in significant pancreatic injuryand a further recent laboratory analysis has suggested that ACE2 receptors, which are utilised by SARS-CoV-2 to gain entry to host cells, are highly expressed on cholangiocytes at a comparable level to type II alveolar cells. Whilst the ultimate cause of cholangitis will remain unknown in this patient, this case highlights the potential for atypical presentations and extra-pulmonary manifestations of COVID-19. Case report - Key learning points COVID-19 is a multi-system illness which can cause significant extra-pulmonary as well as pulmonary pathology, with emerging reports that the biliary tract and pancreas are frequently affected.Evidence to inform accurate prediction of which patients with rheumatic diseases are at highest risk of acquiring severe COVID-19 disease remains insufficient, with current shielding guidelines based on expert consensus.This case highlights the importance of widespread testing for COVID-19 in hospital patients, as not all patients carrying the SARS-CoV-2 virus will demonstrate classical respiratory features of the disease at the point of admission.

Hepatitis A in children: evaluation of atypical manifestations

Background Although hepatitis A infection is known as a benign, self-limited disease without chronicity, the rate of complications increases over time.
 Objective To evaluate atypical manifestations of hepatitis A infection in children.
 Methods A total of 130 children with hepatitis A infection were reviewed. Subjects’ demographic and clinical characteristics, laboratory examinations, and clinical courses were evaluated retrospectively.
 Results Twenty-one subjects had atypical manifestations of disease as follows: immune thrombocytopenic purpura (1 patient), pleural effusion (1), autoimmune hepatitis and hemolytic anemia (1), nephrotic syndrome (2), meningoencephalitis (2), autoimmune hepatitis (2), acalculous cholecystitis (3), relapsing hepatitis (4), and fulminant hepatitis (5). Only gender was significantly different, with males having more atypical manifestations than females (P=0.03). Mortality rate was 3% (3 patients with fulminant hepatitis and 1 with meningoencephalitis died in the intensive care unit).
 Conclusion Although hepatitis A virus infection has a benign, self-limited course without chronicity, recognition of atypical cases which carry mortality risk is important.

Chikungunya in Indonesia: Epidemiology and diagnostic challenges.

Chikungunya virus (CHIKV) is often overlooked as an etiology of fever in tropical and sub-tropical regions. Lack of diagnostic testing capacity in these areas combined with co-circulation of clinically similar pathogens such as dengue virus (DENV), hinders CHIKV diagnosis. To better address CHIKV in Indonesia, an improved understanding of epidemiology, clinical presentation, and diagnostic approaches is needed. Acutely hospitalized febrile patients ≥1-year-old were enrolled in a multi-site observational cohort study conducted in Indonesia from 2013 to 2016. Demographic and clinical data were collected at enrollment; blood specimens were collected at enrollment, once during days 14 to 28, and three months after enrollment. Plasma samples negative for DENV by serology and/or molecular assays were screened for evidence of acute CHIKV infection (ACI) by serology and molecular assays. To address the co-infection of DENV and CHIKV, DENV cases were selected randomly to be screened for evidence of ACI. ACI was confirmed in 40/1,089 (3.7%) screened subjects, all of whom were DENV negative. All 40 cases initially received other diagnoses, most commonly dengue fever, typhoid fever, and leptospirosis. ACI was found at five of the seven study cities, though evidence of prior CHIKV exposure was observed in 25.2% to 45.9% of subjects across sites. All subjects were assessed during hospitalization as mildly or moderately ill, consistent with the Asian genotype of CHIKV. Subjects with ACI had clinical presentations that overlapped with other common syndromes, atypical manifestations of disease, or persistent or false-positive IgM against Salmonella Typhi. Two of the 40 cases were possibly secondary ACI. CHIKV remains an underdiagnosed acute febrile illness in Indonesia. Public health measures should support development of CHIKV diagnostic capacity. Improved access to point-of-care diagnostic tests and clinical training on presentations of ACI will facilitate appropriate case management such as avoiding unneccessary treatments or antibiotics, early response to control mosquito population and eventually reducing disease transmission.

Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent.

BackgroundAmong the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent.Methods and findingsA literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term ‘‘leishmaniasis” and “leishmaniasis epidemiology” alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism.ConclusionsThe increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.

UNIPARENTAL DISOMY OF CHROMOSOME 1 CAUSING CONCURRENT CHARCOT-MARIE-TOOTH AND GAUCHER DISEASE TYPE 3

Uniparental disomy (UPD) can be the cause of atypical disease manifestations in patients with Mendelian disorders. Consideration of this disease mechanism proved essential in our evaluation of a 3-year-old boy, referred to the NIH Clinical Center for further evaluation of Gaucher disease (GD). ### Case report. The patient was born at term to non-consanguineous parents with a paternal family history of autosomal dominant Charcot-Marie-Tooth disease type I (CMT1). His medical history included moderate sensorineural hearing loss, Wolff-Parkinson-White arrhythmia, bicuspid aortic valve, and motor delay, ambulating at 26 months. At 17 months, hepatosplenomegaly was noted and a bone marrow biopsy led to the diagnosis of type 3 GD. Molecular analysis revealed homozygosity for the NM_000157.2:c.1448T>C (L444P) mutation in the glucocerebrosidase gene ( GBA ). He began enzyme replacement therapy (Imiglucerase, 120 U/kg biweekly), with significant resolution of his organomegaly. On examination, he had mild hepatosplenomegaly, bilateral pes cavus, externally rotated hips, genu valgus, hammertoes, decreased muscle tone, and mild foot drop. Reflexes were depressed in the upper extremities and absent in knees and ankles. Ophthalmologic evaluation revealed nystagmus, dysconjugate gaze, slowed, hypometric horizontal saccades, and decreased pupillary constriction (Adie-like). Nerve conduction studies were 13 …

POSSIBLE SCRUB TYPHUS COINFECTIONS IN THAI AGRICULTURAL WORKERS HOSPITALIZED WITH LEPTOSPIROSIS

Possible coinfections with Orientia tsutsugamushi the causative agent of scrub typhus, were prospectively evaluated in rice farmers hospitalized with leptospirosis in Northeast Thailand. Of 22 adults with leptospirosis diagnosed by the microscopic agglutination test, 9 also had serologic evidence of scrub typhus. Of 9 individuals with possible coinfections, 5 had signs or symptoms typical of scrub typhus and atypical of leptospirosis. Patients who appeared to have mixed infections had significantly higher median platelet counts and significantly lower median serum bilirubin and creatinine concentrations (P < 0.05, Mann-Whitney U test) than did individuals with leptospirosis alone. One patient with serologic evidence of scrub typhus and leptospirosis was treated only with penicillin, to which scrub typhus is not sensitive. Respiratory distress worsened during therapy, and the patient died of respiratory failure. Physicians should consider the possibility of scrub typhus infection in leptospirosis patients who respond poorly to treatment or who have atypical disease manifestations.

Lower Lobe Tuberculosis

Development of modern diagnostic procedures has greatly increased our knowledge of chronic pulmonary diseases. New and improved laboratory methods, bronchoscopy, biopsy technics, and serial roentgenographic observations have served not only as an aid to the earlier recognition of these conditions, but also to facilitate the identification of atypical disease manifestations. As a result of the additional knowledge gained through these sources, it has become necessary to revise certain fundamental concepts of chronic pulmonary diseases which, heretofore, have been regarded as almost axiomatic. This has been particularly true in regard to our understanding of the nature and localization of the initial lesion in progressive pulmonary tuberculosis of the reinfection or adult type. Formerly, it was believed that the first lesion in active tuberculosis almost always began in or near the apex of the lung. We now know, however—mainly because of the observations of Assmann (1)—that this lesion frequently occurs in ...