Skin fragility and wound management in Ehlers- Danlos Syndrome: a report by the Ehlers Danlos Syndrome society skin working group.

The Ehlers-Danlos Syndromes (EDS) are a heterogenous group of heritable connective tissue disorders, characterised by joint hypermobility, skin hyperextensibility and generalised tissue fragility. In all types of EDS skin wound healing is impaired to a variable degree. Additional support through wound management plans may help to improve these outcomes, however, there is paucity of evidence regarding clinical management of skin fragility and wounds in EDS. This paper aims to review current evidence and provide recommendations for management of skin wounds in EDS types. Preventative measures to avoid skin injury are strongly recommended, including avoidance of high impact sport and use of appropriate protection such as shin guards. Bruising is common and some types of EDS are associated with haematoma formation with management including compression bandages and consideration of pharmacological therapy. Skin fragility and tears should be managed with a focus on protection of remaining tissue, avoidance of wound tension and low adherence dressings to avoid further injury. This paper provides clear recommendations to address skin management for this group of patients. It highlights the lack of good quality published data to support treatment decisions.

Extracutaneous features and complications of the Ehlers-Danlos syndromes: A systematic review.

Introduction: The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with variable fragility to skin, soft tissue, and certain internal organs, which can cause significant complications, particularly arterial rupture, bowel perforation and joint difficulties. Currently, there are 14 proposed subtypes of EDS, with all except one subtype (hypermobile EDS) having an identified genetic etiology. An understanding of the extracutaneous features and complications within each subtype is key to maximizing clinical care and reducing the risk of further complications. Methods: A systematic review of EDS-related extracutaneous features and complications was undertaken. Results: We identified 839 EDS cases that met the inclusion criteria. We noted a high prevalence of joint hypermobility amongst kyphoscoliotic (39/39, 100%), spondylodysplastic (24/25, 96.0%), and hypermobile (153/160, 95.6%) EDS subtypes. The most common musculoskeletal complications were decreased bone density (39/43, 90.7%), joint pain (217/270, 80.4%), and hypotonia/weakness (79/140, 56.4%). Vascular EDS presented with cerebrovascular events (25/153, 16.3%), aneurysm (77/245, 31.4%), arterial dissection/rupture (89/250, 35.5%), and pneumothorax/hemothorax. Chronic pain was the most common miscellaneous complication, disproportionately affecting hypermobile EDS patients (139/157, 88.5%). Hypermobile EDS cases also presented with chronic fatigue (61/63, 96.8%) and gastrointestinal complications (57/63, 90.5%). Neuropsychiatric complications were noted in almost all subtypes. Discussion: Understanding the extracutaneous features and complications of each EDS subtype may help diagnose and treat EDS prior to the development of substantial comorbidities and/or additional complications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308151, identifier CRD42022308151.

Dermatologic manifestations and diagnostic assessments of the Ehlers-Danlos syndromes: A clinical review.

BACKGROUND: The Ehlers-Danlos syndromes (EDSs) comprise a group of connective tissue disorders that manifest with skin hyperextensibility, easy bruising, joint hypermobility and fragility of skin, soft tissues, and some organs. A correct assessment of cutaneous features along with the use of adjunct technologies can improve diagnostic accuracy. OBJECTIVES: To systematically review the cutaneous features and adjunct investigations of EDS. METHODS: A search of PubMed and Web of Science for EDS-related cutaneous features and additional investigations was undertaken from publication of the 2017 International Classification of EDS until January 15, 2022. RESULTS: One-hundred-and-forty studies involved 839 patients with EDS. The EDS female-to-male ratio was 1.36:1 (P < .001). A high prevalence of skin hyperextensibility, bruising, and soft skin were noted. Most patients with vascular Ehlers-Danlos syndrome showed venous visibility, skin fragility, and acrogeria. Classical EDS showed subcutaneous spheroids and molluscoid pseudotumours. In patients that underwent skin biopsies, only 30.3% and 71.4% showed features suggestive of EDS using light microscopy and transmission electron microscopy, respectively. LIMITATIONS: Retrospective study and small cases numbers for some EDS-subtypes. CONCLUSIONS: An accurate clinical diagnosis increases the chances of a molecular diagnosis, particularly for rarer EDS subtypes, whilst decreasing the need for genetic testing where there is a low clinical suspicion for a monogenic EDS-subtype.

The role of cutaneous manifestations in the diagnosis of the Ehlers-Danlos syndromes.

The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with features of skin hyperextensibility, joint hypermobility, abnormal scarring and fragility of skin, blood vessels and some organs. The disease is generally diagnosed through the cluster of clinical features, though the addition of genetic analysis is the gold standard for diagnosis of most subtypes. All subtypes display skin manifestations, which are essential to the accurate clinical diagnosis of the condition. Furthermore, cutaneous features can be the first and/or only presenting feature in some cases of EDS and thus understanding these signs is vital for diagnosis. This review focuses on particular cutaneous features of each EDS subtype and their clinical importance. Provision of a specific diagnosis is important for management, prognosis and genetic counselling, often for family members beyond the individual.

The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease.

BACKGROUND: Granulomatous and lymphocytic interstitial lung disease (gl-ILD) is a major cause of morbidity and mortality among patients with common variable immunodeficiency. Corticosteroids are recommended as first-line treatment for gl-ILD, but evidence for their efficacy is lacking. OBJECTIVES: This study analyzed the effect of high-dose corticosteroids (≥0.3 mg/kg prednisone equivalent) on gl-ILD, measured by high-resolution computed tomography (HRCT) scans, and pulmonary function test (PFT) results. METHODS: Patients who had received high-dose corticosteroids but no other immunosuppressive therapy at the time (n = 56) and who underwent repeated HRCT scanning or PFT (n = 39) during the retrospective and/or prospective phase of the Study of Interstitial Lung Disease in Primary Antibody Deficiency (STILPAD) were included in the analysis. Patients without any immunosuppressive treatment were selected as controls (n = 23). HRCT scans were blinded, randomized, and scored using the Hartman score. Differences between the baseline and follow-up HRCT scans and PFT were analyzed. RESULTS: Treatment with high-dose corticosteroids significantly improved HRCT scores and forced vital capacity. Carbon monoxide diffusion capacity significantly improved in both groups. Of 18 patients, for whom extended follow-up data was available, 13 achieved a long-term, maintenance therapy independent remission. All patients with relapse were retreated with corticosteroids, but only one-fifth of them responded. Two opportunistic infections were found in the corticosteroid treatment group, while overall infection rate was similar between cohorts. CONCLUSIONS: Induction therapy with high-dose corticosteroids improved HRCT scans and PFT results of patients with gl-ILD and achieved long-term remission in 42% of patients. It was not associated with major side effects. Low-dose maintenance therapy provided no benefit and efficacy was poor in relapsing disease.

Dengue and COVID-19 co-infections: an important consideration in the tropics.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected >370 million individuals worldwide. Dengue is endemic in many countries and leads to epidemics at frequent intervals. In the tropics and subtropics, it is possible that individuals may be concurrently infected with both dengue and SARS-CoV-2. Differentiation between the two infections may be difficult from both a clinical and laboratory perspective. We have outlined the currently published findings (as of the end of December 2021) on patients with dengue and SARS-CoV-2 co-infections and have discussed the observed outcomes and management of such patients. Co-infections were more common in males >25 y of age, fever was not universal, 30-50% had medical comorbidities such as diabetes mellitus or hypertension and the case fatality rate was 16-28%.

Corticosteroid-induced remission and mycophenolate maintenance therapy in granulomatous lymphocytic interstitial lung disease: long-term, longitudinal change in lung function in a single-centre cohort.

Aim: The aim of the study was to evaluate the response in lung function to different treatment regimens for common variable immunodeficiency patients with granulomatous lymphocytic interstitial lung disease (GLILD). Method: A longitudinal retrospective cohort study was carried out. Patients were divided into three groups. To assess the response to different treatments, we compared baseline lung function with post-treatment tests. Results: 14 patients with GLILD were included, seven of whom were treated with acute corticosteroids for a mean duration of 132±65 days. Spirometry results were unchanged, but there was a significant improvement in diffusing capacity of the lung for carbon monoxide (D LCO)% and transfer coefficient of the lung for carbon monoxide (K CO)% (median change in D LCO%=7%, p=0.04, and K CO%=13%, p=0.02). Relapse occurred in three out of seven patients. Five patients were treated with long-term mycophenolate mofetil (MMF) with/without corticosteroids for a mean duration of 1277±917 days. No changes were found in spirometry; however, there was a significant increase in D LCO% and K CO% (median change in each of D LCO% and K CO%=10%, p=0.04). Four patients on steroids with MMF successfully weaned the prednisone dose over 12 months. Four patients never received immunosuppression therapy. A significant decline was found in their lung function assessed over 7.5 years. The median reduction in the forced vital capacity (FVC)%, forced expiratory volume in 1 s (FEV1)% and D LCO% was 15%, 7% and 15%, equivalent to 2%, 1% and 2% per year, respectively. Conclusion: Corticosteroids improve gas transfer in GLILD, but patients often relapse. The use of MMF was associated with long-term effectiveness in GLILD and permits weaning of corticosteroids. A delay in initiating and continuing maintenance treatment could lead to disease progression.

Diagnosis of Apis dorsata venom allergy: use of recombinant allergens of Apis mellifera and a passive basophil activation test.

BACKGROUND: Allergy to Apis dorsata (Giant Asian Honeybee) venom is the commonest insect allergy in Sri Lanka and South East Asia. However, laboratory diagnosis is difficult as the pure venom and diagnostic reagents are not commercially available. OBJECTIVE: This study assessed the use of four recombinant allergens of A. mellifera venom and the passive basophil activation test in the diagnosis of A. dorsata venom anaphylaxis. METHODS: Serum IgE levels to four recombinant allergens of A. mellifera, rApi m 1, 2, 5 and 10 were assessed and compared with serum IgE to the crude venom of A. mellifera or V. vulgaris by Phadia ImmunoCAP, in patients who developed anaphylaxis to A. dorsata stings. Basophil activation in response to venom of A. dorsata or V. affinis was assessed using a passive basophil activation test. Association of the severity of the reaction with basophil activation was compared. RESULTS: rApi m 1 and 10 combinedly had significant correlation (r = 0.722; p < 0.001) with the crude venom of A. mellifera (Western honeybee) and a higher positivity rate of 90% (27/30). Whereas, IgE reactivity to rApi m 2 or 5 had significant correlation (p = 0.02 and p = 0.005 respectively) with V. vulgaris crude venom. All 30 (100%) were positive to A. dorsata venom in passive BAT; 70% (21/30) had over 80% activation, 96.7% (29/30) had over 60% activation and 100% had over 50% activation. Percentage activation of basophils in patients who had mild or moderate reactions (n = 20) was significantly low (p = 0.02) from that of patients who had severe reactions (n = 10). CONCLUSIONS: rApi m 1 and 10 when combined was sensitive for the diagnosis of A. dorsata allergy. This combination had the lowest cross-reactivity rate with Vespula vulgaris. The passive BAT is highly sensitive in A. dorsata allergy. The basophil reactivity was significantly higher in severe anaphylaxis compared to mild/moderate anaphylaxis. This finding should be further explored in further studies.

Postdischarge outcomes of COVID-19 patients from South Asia: a prospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause clinical manifestations that last for weeks or months after hospital discharge. The manifestations are heterogeneous and vary in their frequency. Their multisystem nature requires a holistic approach to management. There are sparse data from the South Asian region on the outcomes of hospital-discharged COVID-19 patients. We assessed the posthospital discharge outcomes of a cohort of Sri Lankan COVID-19 patients and explored the factors that influenced these outcomes. METHODS: Data were prospectively collected from patients who were discharged following an admission to the Nawaloka Hospital, Sri Lanka with COVID-19 from March to June 2021. At discharge, their demographic, clinical and laboratory findings were recorded. The patients were categorised as having mild, moderate and severe COVID-19, based on the Sri Lanka Ministry of Health COVID-19 guidelines. Following discharge, information on health status, complications and outcomes was collected through clinic visits and preplanned telephone interviews. A validated (in Sri Lanka) version of the Short Form 36 health survey questionnaire (SF-36) was used to assess multi-item dimensions health status of the patients at 1, 2 and 3 mo postdischarge. RESULTS: We collected data on 203 patients (male, n=111 [54.7%]). The level of vaccination was significantly associated with disease severity (p<0.001). Early recovery was seen in the mild group compared with the moderate and severe groups. At 3 mo, on average 98% of mild and 90% of moderate/severe patients had recovered. Based on the SF-36, physical functioning dimensions, role limitation due to physical and emotional health, energy/ fatigue, emotional well-being, social functioning, pain and general health were significantly different in the moderate/severe vs mild COVID-19 groups at 1, 2 and 3 mo postdischarge (p<0.05). Twenty-three patients developed complications, of which the most common were myocardial infarction with heart failure (n=6/23; 26.1%), cerebrovascular accident (n=6/23; 26.1%) and respiratory tract infections (n=3/23; 13.01%) and there were six deaths. CONCLUSIONS: In our cohort, receiving two doses of the COVID-19 vaccine was associated with reduced disease severity. Those with mild disease recovered faster than those with moderate/severe disease. At 3 mo posthospital discharge, >90% had recovered.

COVID-19 vaccination in cancer patients: a narrative review.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 220 million individuals worldwide, and has been shown to cause increased disease severity and mortality in patients with active cancer versus healthy individuals. Vaccination is important in reducing COVID-19-associated morbidity and mortality. Thus, the aim of this article was to review the existing knowledge on effectiveness, immunogenicity and safety of COVID-19 vaccines in patients with cancer. Fifty-four articles were included following a search of PubMed and Google Scholar databases for studies published between January 2020 and September 2021 that investigated humoral and cell-mediated immune responses following COVID-19 vaccination in patients with cancer. Immunogenicity of vaccines was found to be lower in patients with cancer versus healthy individuals, and humoral immune responses were inferior in those with haematological versus solid cancers. Patient-, disease-, and treatment-related factors associated with poorer vaccine responses should be identified and corrected or mitigated when possible. Consideration should be given to offering patients with cancer second doses of COVID vaccine at shorter intervals than in healthy individuals. Patients with cancer warrant a third vaccine dose and must be prioritized in vaccination schedules. Vaccine adverse effect profiles are comparable between patients with cancer and healthy individuals.

COVID-19 in cancer patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has currently affected >220 million individuals worldwide. The complex interplay of immune dysfunction, active malignancy, the effect of cancer treatment on the immune system and additional comorbidities associated with cancer and COVID-19 all affect the outcomes of COVID-19 in patients with cancer. We have discussed the published findings (through the end of September 2021) on the effects of cancer on the morbidity and mortality of COVID-19, common factors between cancer and COVID-19, the interaction of cancer and COVID-19 treatments, the impact of COVID-19 on cancer clinical services, immune test findings in cancer patients with COVID-19 and the long-term effects of COVID-19 on cancer survivors.

Involvement of the Liver in COVID-19: A Systematic Review.

COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.

The immature platelet fraction, a predictive tool for early recovery from dengue-related thrombocytopenia: a prospective study.

BACKGROUND: There is a paucity of predictive factors for early recovery from thrombocytopenia related to dengue. The immature platelet fraction (IPF%) is reflective of megakaryopoiesis and may correlate with recovery from dengue-related thrombocytopenia. Our objective was to assess the predictive value of IPF% on days 2 and 3 of illness for recovery from dengue-related thrombocytopenia. METHODS: A prospective study was conducted among patients with dengue admitted to our institution (Nawaloka Hospital PLC) from December 2019 to October 2020. Dengue was diagnosed based on positive non-structural antigen 1 or IgM. IPF% data were extracted from the Sysmex-XN-1000 automated hematology analyzer. Clinical data were obtained from electronic medical records. Statistical analyses were performed using SPSS version 20. RESULTS: We included 240 patients. An IPF% on day 2 of illness of >7.15% had a sensitivity of 80.0% and specificity of 70.4% for prediction of platelet recovery (defined as platelet count ≥60×109/L) on day 7 of illness. An IPF% of >7.25% on day 3 of illness had a sensitivity of 88.9% and specificity of 47.1% for predicting platelet recovery >60×109/L on day 8 of illness. The IPF% was significantly lower in patients with severe dengue. Platelet recovery was observed within 48 h after the peak IPF% was reached, regardless of severity. CONCLUSION: We propose that IPF% values on days 2 and 3 of illness are a promising predictive tool for early recovery from dengue-related thrombocytopenia.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Therapeutic options for CTLA-4 insufficiency.

BACKGROUND: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. OBJECTIVE: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. METHODS: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. RESULTS: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. CONCLUSION: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.

Combination of cycle threshold time, absolute lymphocyte count and neutrophil:lymphocyte ratio is predictive of hypoxia in patients with SARS-CoV-2 infection.

BACKGROUND: There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation <92%). METHODS: Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities. RESULTS: RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46±2.64 vs 22.62±3.37, p=0.0001; AL, RC vs not: 531.49±289.09 vs 764.69±481.79, p=0.0001; NLR, RC vs not: 3.42±0.75 vs 2.59±0.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct <19.9, AL <630.8×103/µL and NLR >3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power. CONCLUSIONS: Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness.

Genetic Analysis of a Cohort of 275 Patients with Hyper-IgE Syndromes and/or Chronic Mucocutaneous Candidiasis.

Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.

Admission ultrasonography as a predictive tool for thrombocytopenia and disease severity in dengue infection.

BACKGROUND: Ultrasound (US) is an investigation available in many acute care settings. Thrombocytopenia is a well-described complication of dengue infection and has been shown to correlate with disease severity. The purpose of this study was to assess the utility of admission ultrasonography in predicting thrombocytopenia and disease severity in patients infected with dengue virus. METHODS: Data were collected prospectively on 176 patients (male, n=86; female, n=90) admitted to the Nawaloka Hospital, Sri Lanka with dengue infection between December 2016 and August 2018. All patients had an US scan on admission and disease severity was determined using the World Health Organization 2009 classification. RESULTS: There were 106 (60.2%) cases of dengue with/without warning signs and 70 (39.8%) cases of severe dengue. Patients with an abnormal US on admission were more likely to have severe dengue. Gallbladder wall thickening was the most common US abnormality. Abnormal US findings significantly correlated with more pronounced thrombocytopenia from day 2 of admission. CONCLUSIONS: An abnormal US scan on admission can aid in identification of patients at risk of developing severe dengue and can be used as a novel clinical tool to identify patients at risk of severe thrombocytopenia.

Nephrotoxicity and neurotoxicity following star fruit (Averrhoa carambola) ingestion: a narrative review.

In recent times, star fruit (Averrhoa carambola) nephrotoxicity and neurotoxicity have been increasingly reported, both in individuals with pre-existing renal disease and those with previously normal renal function. We summarise the clinical findings of star fruit toxicity in humans and outline the important pathogenetic insights provided by animal studies. Google Scholar, EMBASE, Scopus and PubMed were searched from 1995 through July 2020 for case reports/series on renal or neurological manifestations of star fruit toxicity in humans and mechanisms of star fruit toxicity in animal studies. Ten case series and 28 case reports in humans (total number of individuals=136) were included and 8 animal studies were analysed. Ninety-four (69.1%) patients had prior renal impairment. Renal histology showed acute oxalate nephropathy with tubulointerstitial nephritis or tubular necrosis. Neurotoxicity manifestations ranged from hiccups to status epilepticus. Oxalate and caramboxin are considered the main substances causing nephrotoxicity and neurotoxicity. Caramboxin inhibits GABA binding and activates the glutamatergic receptors. Haemodialysis improved outcomes in neurotoxicity. Nephrotoxicity and neurotoxicity need to be looked for with star fruit toxicity, both in individuals with abnormal or normal renal function. Once star fruit intoxication is identified, early renal replacement therapy should be considered. Further studies on the mechanisms of star fruit toxicity are needed.

Gastrointestinal manifestations in COVID-19.

Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome-related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4-61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.