Severe Systemic Manifestations Research Articles

Case – Late Presentation of Invasive Keratinizing Squamous Cell Carcinoma

Penile cancer, a rare but highly morbid disease, primarily manifests as squamous cell carcinoma (PSCC) originating from the squamous cells of the glandular and preputial skin. Late-stage diagnosis is common due to social stigma, psychological barriers, and nonspecific initial symptoms, resulting in poor overall survival rates, especially in metastatic cases. This case report illustrates a 38-year-old man with advanced metastatic PSCC, showcasing severe systemic manifestations and delayed presentation of the disease. Despite aggressive treatment options, the patient opted for palliative care, succumbing to the disease months after his diagnosis. Risk factors for PSCC include HPV infection, phimosis, chronic inflammation, and lifestyle factors, with higher prevalence in regions of low socioeconomic status. The psychological and sexual burden of penile cancer is significant, impacting patients’ well-being, mental health, and quality of life. In conclusion, efforts to reduce the stigma associated with penile cancer are crucial to prompt early diagnosis and treatment initiation. Encouraging seeking medical attention for symptoms can enhance the chances of recovery and minimize the need for invasive treatments. Addressing the psychosocial impact of the disease is imperative for holistic patient care.

Periumbilical purpuric rash as a clue to the diagnosis of strongyloidiasis and HTLV-1 infection

ABSTRACT Strongyloidiasis is a parasitic disease caused by the nematode Strongyloides stercoralis, widely distributed in Brazil. In general, it manifests with nonspecific gastrointestinal symptoms. However, in severe cases, pulmonary, neurological and systemic manifestations may occur, culminating in high mortality rates. Exceptionally, there may be a single-appearing periumbilical purpuric eruption. The prognosis is related to the rapid diagnosis and to beginning of the therapy. The case of an elderly man, former alcoholic, with chronic abdominal pain, fever and unexplained weight loss, in addition to periumbilical purpura is reported on this study. The manifestation motivated a specific investigation in which resulted in the diagnosis of strongyloidiasis and infection by human T-lymphotropic virus 1 (HTLV-1). KEY WORDS: Strongyloidiasis; Strongyloides stercoralis; HTLV-1; Purpura

Crush syndrome: a review of current knowledge and treatment strategies

Crush syndrome is a severe systemic manifestation resulting from the breakdown of muscle cells leading to the release of toxic substances into the bloodstream. This condition can occur when a part of the body experiences a significant amount of pressure for an extended period. Crush syndrome presents with severe metabolic disruptions such as acute kidney injury, electrolyte disturbances, and cardiovascular collapse. It is essential to understand the pathophysiology and clinical features of crush syndrome for effective management and prevention of potentially devastating outcomes. The act of crushing and rupturing muscular cells generates a mechanical force that triggers the discharge of myoglobin. Subsequently, myoglobin undergoes a conversion into metmyoglobin and acid hematin, which are subsequently released into the systemic circulation. The muscular tissue harbors a variety of electrolytes and enzymes, which may attain toxic levels upon entry into the circulation in excessive quantities. The release of sodium, calcium, and fluids due to regional ischemia leads to increased muscle volume and tension, depletion of creatine kinase (CK) and ATP, and muscle vasodilation, further exacerbating hypotension. Crush syndrome can also lead to cardiovascular instability and renal failure due to vasomotor and nephrotoxic factors. Elevations in serum CK levels exceeding 1000 IU/l, along with accompanying clinical features, are widely recognized as indicative of crush syndrome. Diagnostic investigations commonly involve assessing serum levels of aldolase, myoglobin, and myoglobin degradation products. Progressive increases in serum levels of lactic acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) are observed, while levels of serum urea and creatinine exhibit a steep rise, particularly following prolonged compression, and serve as valuable predictors of renal failure. The treatment of crush syndrome requires a multidisciplinary approach that addresses the metabolic, cardiovascular, and renal complications associated with this condition. The mainstay of treatment includes early release of the affected limb or compartment, fluid resuscitation, correction of electrolyte abnormalities, and alkalinization of urine. Additionally, renal replacement therapy and hyperbaric oxygen therapy may be beneficial in managing acute kidney injury and tissue hypoxia, respectively. Crush syndrome, albeit infrequent, represents a potentially fatal medical condition that demands a thorough comprehension of its underlying pathophysiology, clinical manifestations, and treatment modalities. Early recognition and appropriate management of this condition can significantly r,educe morbidity and mortality associated with crush syndrome.

EGPA/Hypereosinophilic Overlap Syndrome in two 16-year-old patients

Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Hypereosinophilic syndrome are two eosinophilic diseases that can result in severe systemic manifestations. Generally, they are rare in children.

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children.

Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis. A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP. The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram. Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.

LUNG DAMAGE AS A COMPLICATION OF SYSTEMIC JUVENILE ARTHRITIS

According to modern science, systemic juvenile arthritis (sJA) is an autoinflammatory disease characterized by severe systemic manifestations and life-threatening complications. This article discusses the developmental predictors, clinical and radiological manifestations and pathogenetic features of the disease. Particular attention is paid to genetically engineered biological therapy.&#x0D; Numerous pulmonary complications are now known in sJA children, including interstitial lung disease (ILD), pulmonary alveolar proteinosis (PAP), pulmonary hypertension (PH), and lipoid pneumonia. Fatality rate in sJA patients increases against the macrophage activation syndrome (MAS) development and pulmonary hypertension, which occurs with proliferation of endothelial cells, muscle tissue and fibroblasts in the lungs vessels. A more severe disease progression is typical for children with genetic defects. SAM and PAP relapses are observed more often in such patients. Instrumental diagnostic methods helped to identify, 5 subtypes determining the lung tissue damage in sJA. Computer tomography (CT) revealed the main signs of lung damage in sJA patients: ground-glass opacity, crazy-paving sign, thickening of the bronchial wall, interlobar septum, pleura, peripheral consolidation, and lymphadenopathy. Due to the high level of sJA activity, children were prescribed genetically engineered biological drugs (GEBP). Timely therapeutic correction is necessary to exclude life-threatening adverse reactions. Under dynamic observation, it is possible to diagnose lung damage in children at the early stage and to control the pathology.&#x0D; The purpose of this review is to systematize the existing data on developmental predictors, pathogenetic features of the disease, sJA clinical and radiological manifestations, and genetically engineered biological therapy as a method of sJA treatment.

S1818 Rare Sequelae of Obstructive Jaundice: Hyperferritinemia and Bile Cast Nephropathy

Introduction: Obstructive jaundice occurs due to a physical blockage in the biliary outflow tract or external compression. While jaundice and scleral icterus are common symptoms initially, long term sequelae include severe systemic manifestations from the buildup of various compounds normally excreted in bile such as bilirubin. Case Description/Methods: A 67-year-old male smoker presented with 3 weeks of pruritus, acholic stools, dark urine, nausea, vomiting, and 20-pound weight loss. Physical exam was notable for jaundice and scleral icterus, LUQ and epigastric tenderness to palpation, but lacked hepatosplenomegaly, ascites or other stigmata of cirrhosis. Liver function tests showed AST 486 IU/L, Alk Phos 1419 IU/L, Alt 600 IU/L, and total bilirubin >30.0 mg/dL with direct bilirubin >10.0 mg/dL. Ferritin was >7500 ng/mL with decreased transferrin of 159 mcg/dL. Hepatitis panel and malignancy/autoimmune markers were negative. CMP showed BUN 74 mg/dL, and creatinine 5.1 mg/dL with 2+bilirubin on urinalysis and microscopic analysis showing pigmented renal tubular cells, bilirubin crystals, and waxy casts suggestive of ATN due to bilirubin damage and possible CKD given waxy casts (Table). CT abdomen reported severe intra and extra hepatic biliary duct dilation with CBD of 17 mm and abrupt tapering with pancreatic head fullness confirmed with MRCP. On day 2, ERCP showed a tight 15mm distal biliary stricture. A small sphincterotomy followed by balloon dilation allowed for placement of a CBD stent with excellent drainage of dark green bile. Following ERCP, patient had a drop of liver function tests and ferritin levels, gradual improvement in BUN and creatinine, and was discharged in stable condition on hospital day 6. On day 16, EUS revealed a hypoechoic area within the periampullary area with atypical cells in brushings collected during repeat ERCP (Figure). Discussion: Iron and iron binding proteins have been shown to be excreted in bile, primarily in iron excess. Our patient showed a large increase in ferritin signifying the potential role of biliary excretion of excess ferritin, with unknown ramifications. Additionally, severe biliary tree obstruction led to markedly elevated bilirubin, overwhelming renal clearance leading to severe tubular damage. With alleviation of obstruction, there was a steady decrease in ferritin and return to normal baseline renal function. Further research is needed to clarify both the consequences of excess ferritin in biliary obstruction and the significance of excess bilirubin in renal injury.Figure 1.: a) Ampulla prior to ERCP on day 2 shows no periampullary abnormality. b) Day 16 - Endoscopic Ultrasound showing narrowing of distal common bile duct with hypoechoic intraductal area. c) Bile casts and bilirubin crystals seen on microscopy. Table 1. - Patient’s Laboratory test results on and post admission Laboratory Values Reference Range Day 1 Day 5 (3 days post-ERCP) Day 21 AST 13 – 39 IU/L 486 187 18 ALT 7 – 52 IU/L 600 315 27 Alkaline Phosphatase 34 – 104 IU/L 1419 886 160 Total Bilirubin 0.3 - 1.2 mg/dL >30.0 13.0 4.4 Albumin 3.5 - 5.2 g/ 3.0 2.9 3.4 BUN 7 – 25 mg/dL 74 64 18 Creatinine 0.5 - 1.2 mg/dL 5.1 2.90 1.01 WBC 4 – 11 K/cmm 13.8 17.7 10.1 Hgb 13.7 - 17.5 g/dL 11.9 9.4 8.5 Ferritin 24 – 336 >7500 4677 976 Transferrin 300 to 360 mcg/dL 159 233 Iron 50 - 182 ug/dL 126 61 Iron Saturation 57% 19% TIBC 250 – 450 ug/dl 233 326 Urine Bilirubin Negative 2+ Negative Urobilinogen 0.0 - 2.0 EU/dL 4.0 < 2.0 PT 9.1 - 13.2 sec 26.6 12.8 PTT 23.3 - 36.6 SEC 42.0 33.0 INR 0.8 - 1.2 2.3 1.1 Alpha-1-Antitrypsin (ATT) 83 – 199 mg/dL 256 Ceruloplasmin 18– 36 mg/dL 51 Carcinoembryonic Antigen (CEA) 0.0 - 3.0 ng/mL 3.9

Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection.

BackgroundSevere acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation.ObjectivesPulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin.Method31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control.ResultsWe measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, were positively correlated with sign of endothelial damage in those patients as determined by plasma levels of LDH. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro.ConclusionsOur results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.

Predicting Sustained Clinical Response to Rituximab in Moderate to Severe Systemic Manifestations of Primary Sjögren Syndrome.

ObjectiveTo assess outcomes of repeat rituximab cycles and identify predictors of sustained clinical response in systemic manifestations of primary Sjögren syndrome (pSS).MethodsAn observational study was conducted in 40 rituximab‐treated patients with pSS. Clinical response was defined as a 3‐point or more reduction in the European League Against Rheumatism (EULAR) Sjögren Disease Activity Index (ESSDAI) at 6 months from baseline. Peripheral blood B cells were measured using highly sensitive flow cytometry. Predictors of sustained response (within two rituximab cycles) were analyzed using penalized logistic regression.ResultsThirty‐eight out of 40 patients had moderate to severe systemic disease (ESSDAI >5). Main domains were articular (73%), mucocutaneous (23%), hematological (20%), and nervous system (18%). Twenty‐eight out of 40 (70%) patients were on concomitant immunosuppressants. One hundred sixty‐nine rituximab cycles were administered with a total follow‐up of 165 patient‐years. In cycle 1 (C1), 29/40 (73%) achieved ESSDAI response. Of C1 responders, 23/29 received retreatment on clinical relapse, and 15/23 (65%) responded. Of the 8/23 patients who lost response, these were due to secondary non‐depletion and non‐response (2NDNR; 4/23 [17%] as we previously observed in systemic lupus erythematosus with antirituximab antibodies, inefficacy = 2/23, and other side effects = 2/23). Within two cycles, 13/40 (33%) discontinued therapy. In multivariable analysis, concomitant immunosuppressant (odds ratio 7.16 [95% confidence interval: 1.37–37.35]) and achieving complete B‐cell depletion (9.78 [1.32–72.25]) in C1 increased odds of response to rituximab. At 5 years, 57% of patients continued on rituximab.ConclusionOur data suggest that patients with pSS should be co‐prescribed immunosuppressant with rituximab, and treatment should aim to achieve complete depletion. About one in six patients develop 2NDNR in repeat cycles. Humanized or type 2 anti‐CD20 antibodies may improve clinical response in extra‐glandular pSS.

COVID-19 and Stress Response

The Coronavirus Disease 2019 has become a global public health emergency. The novel coronavirus is becoming more contagious through continuous evolution, it is difficult to prevent transmission. The patients of COVID-19 suffer from severe pneumonia and complex systemic manifestations. Reducing the damage of COVID-19 to the human body becomes particularly important. In this review, we reviewed the similarity and particularity of viral infectious diseases to understand the pathogenic mechanisms of COVID-19 and to explore optimal therapy for COVID-19.

Hypocomplementemic Urticarial Vasculitis Syndrome or Systemic Lupus Erythematosus in Evolution?

Hypocomplementemia urticarial vasculitis syndrome (HUVS) is a rare form of systemic vasculitis which is characterized by the presence of urticaria and hypocomplementemia. The presence of recurrent and chronic urticarial rash is the dominant clinical finding in HUVS. Other manifestations including angioedema, arthritis, gastrointestinal symptoms, ocular inflammation, pulmonary involvement, renal involvement, and central nervous system involvement are also seen. Although the pathophysiology of HUVS is yet to be fully understood, it has been demonstrated that immune complex-mediated injury is the predominant mechanism responsible for severe systemic manifestations; a mechanism of injury similar to systemic lupus erythematosus (SLE). HUVS shared many clinicopathological features with SLE and it is prudent to question whether HUVS is a separate disease entity or SLE in evolution. Herein we present a case of a male patient who was diagnosed with SLE a year after being diagnosed with HUVS.

Lysosphingolipid urine screening test using mass spectrometry for theearly detection of lysosomal storage disorders.

Background: Sphingolipidoses are caused by a defective sphingolipid catabolism, leading to an accumulation of several glycolipid species in tissues and resulting in neurotoxicity and severe systemic manifestations. Methods & results: Urine samples from controls and patients were purified by solid-phase extraction prior to the analysis by ultra-high-performance liquid chromatography (UPLC) combined withMS/MS. A UPLC-MS/MS method for the analysis of 21 urinary creatinine-normalized biomarkers for eight diseases was developed and validated. Conclusion: Considering the growing demand to identify patients with different sphingolipidoses early and reliably, this methodology will be applied for high-risk screening to target efficiently patients with various sphingolipidoses.

Eyelid lesion caused by paracoccidioidomycosis: a case report

Paracoccidioidomycosis is a systemic mycosis of great epidemiological importance in Brazil and has a significant impact on rural workers, mainly in tropical and subtropical regions. The disease is transmitted via inhalation of spores and can cause severe systemic manifestations. Ocular involvement is uncommon, and the differential diagnosis includes a wide range of other diseases, which can make it difficult to identify the condition. Treatment is with systemic antifungal agents, but the disease has a relapsing course and progresses to fibrosis of the affected tissues. The present study aimed to report a case of eyelid lesion caused by paracoccidioidomycosis that was initially misdiagnosed as chalazion. The correct diagnosis was later confirmed using excisional biopsy.

Cutaneous manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a distinct group of systemic vasculitis with severe multi-organ involvement. It includes three types: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). Cutaneous manifestations are present at the time of presentation in around 35% of cases and are more frequently encountered in EGPA than in GPA or MPA. They can also occur during the course of the disease or mark a disease relapse. They can be classified into specific or non-specific according to the presence or absence of vasculitis, whether or not associated with granuloma, in skin biopsies. The most common presentation of vasculitic skin lesions in AAV is palpable purpura. Other manifestations include hemorrhagic blisters, tender subcutaneous nodules, livedo reticularis/racemosa, painful ulcers that may mimic pyoderma gangrenosum (PG), and digital gangrenes. A wide range of non-specific cutaneous manifestations can occur in association with AAV including urticarial rash, prurigo, sterile pustules, and oral lesions. The presence of cutaneous lesions is usually associated with severe organ involvement and systemic manifestations. Since skin lesions in AAV can occur in other types of vasculitis and in other disorders, attributing them to AAV requires meticulous clinical, laboratory, and serological correlation. Awareness of cutaneous lesions of AAV is important for all physicians working in the field of systemic vasculitis as a skin biopsy may provide an easy clue to diagnose AAV in such cases.

Seroprevalence of antibodies against Borrelia burgdorferi sensu lato in healthy blood donors in Romania: an update

BackgroundThe Borrelia burgdorferi sensu lato (s.l.) genogroup is the causative agent responsible for Lyme borreliosis, a common tick-borne infectious disease in some temperate regions of the Northern Hemisphere. In humans, the clinical manifestations of Lyme borreliosis vary from dermatological infection to severe systemic manifestations. In Romania, data on the seroprevalence of Lyme borreliosis and associated risk factors are scarce and outdated, as the only seroprevalence study with a large dataset was published more than 20 years ago. Therefore, the aim of the present study was to evaluate the seroprevalence for Borrelia burgdorferi s.l. in healthy blood donors from six Romanian counties and identify the associated risk factors.MethodsThe study was conducted among 1200 healthy blood donors aged between 18 and 65 years during November 2019 and September 2020 from six counties in the northwestern and central parts of Romania. A two-tiered testing strategy was applied. Positive and equivocal immunoenzymatic test results for IgG and IgM antibodies were further confirmed by Western blot.ResultsSerum samples from 20% of the blood donors had positive or equivocal IgG and IgM ELISA index values. In total, 2.3% of the serum samples for IgG and 1.8% for IgM were positive by Western blot. The seroprevalence for both antibodies varied between 1.5% (Satu-Mare) and 6.5% (Bistrița-Năsăud) in the six counties investigated. The highest seroprevalence was observed in men (4.7%), in blood donors performing their professional activities outdoors (4.2%), and in those aged ≥ 56 years (8%).ConclusionsThese findings confirm the presence of specific IgG and IgM antibodies to B. burgdorferi s.l. among healthy blood donors from Romania. Furthermore, potential risk factors, such as gender, age, and behavior, associated with the presence of positive B. burgdorferi s.l. antibodies among healthy blood donors were identified.Graphical

Organ-specific genome diversity of replication-competent SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not always confined to the respiratory system, as it impacts people on a broad clinical spectrum from asymptomatic to severe systemic manifestations resulting in death. Further, accumulation of intra-host single nucleotide variants during prolonged SARS-CoV-2 infection may lead to emergence of variants of concern (VOCs). Still, information on virus infectivity and intra-host evolution across organs is sparse. We report a detailed virological analysis of thirteen postmortem coronavirus disease 2019 (COVID-19) cases that provides proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of immunocompromised patients, including heart, kidney, liver, and spleen (NCT04366882). In parallel, we identify organ-specific SARS-CoV-2 genome diversity and mutations of concern N501Y, T1027I, and Y453F, while the patient had died long before reported emergence of VOCs. These mutations appear in multiple organs and replicate in Vero E6 cells, highlighting their infectivity. Finally, we show two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma. Our results provide insights about the pathogenesis and intra-host evolution of SARS-CoV-2 and show that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.

Traditional Chinese Medicine in Patients With Primary Sjogren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease mainly characterized by dryness, fatigue, and pain. Current therapies for SS in Western medicine are limited. The purpose of this clinical study was to explore the efficacy and safety of using a traditional Chinese medicine (TCM) formula on patients with primary SS.Methods: We performed a 12-week, randomized, double-blinded, placebo-controlled clinical trial at Chung Shan Medical University Hospital. We included 42 patients with SS between the ages of 20 and 80 years who met the classification criteria of the American and European Consensus Group (AECG). Patients who had other severe systemic manifestations or diseases were excluded from this trial. After screening, patients were randomly assigned to the TCM treatment group or placebo group (ratio of 2:1). We treated the TCM group with 6 g of Gan-Lu-Yin granules after breakfast and 6 g of Jia-Wei-Xiao-Yao-San combined with 1 g of Suan-Zao-Ren-Tang and 1 g of Ye-Jiao-Teng every night after dinner. Patients in the control group were treated with a placebo with the same appearance and flavor but only one-tenth the dosage of that received by the treatment group. The European League Against Rheumatism Sjogren's Syndrome Patient-Reported Index (ESSPRI) was used as the primary endpoint at week 12. Secondary endpoints were the Sjogren's Syndrome Disease Activity Index (SSDAI), physician global assessment (PGA), visual analogue scale (VAS), Multidimensional Fatigue Inventory, Medical Outcomes Survey Short Form-36, and the Pittsburgh Sleep Quality Score (PSQI). Adverse events were also recorded.Results: Of the 42 randomized patients, 28 patients were assigned to the TCM treatment group and 14 patients were assigned to the controlled group. During the study period, 5 patients withdrew from the TCM group and 7 withdrew from the control group. At week 12, the ESSPRI scores of both groups had improved. The ESSPRI score of the treatment group decreased by 0.62 (95% CI P = 0.557) and that of the placebo group decreased by 0.91 (P = 0.557). However, no significant difference was observed between the two groups. Sleep duration in the PSQI was −0.61, which exhibited an improvement of more than the −0.21 compared with the placebo group (P = 0.914).Conclusion: At week 12, the ESSPRI scores did not reveal that the use of the TCM formula was efficacious for treating patients with Sjogren's syndrome. However, the PSQI scores indicated that this formula could prolong patient sleep duration. We also found that this formula could decrease the blood pressure of patients.

English

BACKGROUND Erythroderma is a clinical entity that may cause severe systemic manifestations. The difficulty with erythroderma lies in finding the underlying aetiology. It is imperative to demonstrate precise aetiology whenever possible so that distinct therapy may be initiated. At times, despite finding the aetiology, relapses constitute a great menace. The purpose of our study was to assess the clinical profile and aetiology of erythroderma. Besides, the study also illustrated factors leading to relapses; such studies are rare in literature. METHODS This hospital-based, cross-sectional study included 88 patients of erythroderma of either sex and age more than 18 years; their clinical, laboratory, histopathological findings, treatment and outcome were studied. RESULTS The mean age of onset was 47.3 ± 12.35 years with the male to female ratio being 2.38:1. The most common cause of erythroderma was pre-existing dermatoses (67 %) followed by drugs (10.2 %), infections (3.4 %), malignancies (4.54 %), and idiopathic (14.7 %). Psoriasis was the predominant aetiology (45.4 %) among the pre-existing dermatoses with a maximum number of relapses (P = 0.02). Psoriasis was significantly associated with pruritus (P = 0.001), subungual hyperkeratosis (P = 0.0001), palmoplantar keratoderma (P = 0.001). Clinicohistological association was found in 64.6 % of cases. Mortality was seen in 6.8 % of cases. CONCLUSIONS As in previous studies, pre-existing dermatoses were the most common causes in our study; albeit, a special emphasis on factors leading to relapses was given to prevent further episodes. The most common factor of relapse was uncontrolled comorbid disorders (diabetes and hypertension) followed by medication nonadherence. Hence, our study suggests a need for more effective comorbidity management and creating awareness regarding judicial use of drugs which can go far in preventing mortality and morbidity. KEY WORDS Erythroderma, Adults, Aetiology, Relapses, Comorbidities.

Spectrum of Multiorgan Dysfunction in Scrub Typhus Infection.

We planned this study to determine the clinical spectrum and compare incidence of multiorgan dysfunction in children hospitalized with scrub typhus with other etiologies of tropical fever. Prospective cohort study. Pediatric emergency and PICU services of a university teaching hospital situated in the sub-Himalayan region. Children aged 2 months to 14 years with acute undifferentiated fever of more than 5 days. Detailed fever workup was performed in all children. We compared scrub typhus IgM positive children (cases) with remaining febrile children who were negative for scrub IgM assay (controls) for mortality and morbidity. We enrolled 224 febrile children; 76 children (34%) were positive for scrub typhus IgM ELISA. Scrub typhus group had a significantly higher incidence of multiorgan dysfunction [OR 3.5 (95% CI 2.0-6.3); p < 0.001] as compared to non-scrub typhus group requiring supportive care. The incidence of altered sensorium [OR 8.8 (95% CI 3.1-24.9)], seizures [OR 3.0 (95% CI 1.1-8.3)], acute respiratory distress syndrome [OR 17.1 (95% CI 2.1-140.1)], acute renal failure (5% vs. 0%), meningitis [OR 6.2 (95% CI 1.2-31.6)], thrombocytopenia [OR 2.8 (95% CI 1.5-5.1)], transaminitis [OR 2.7 (95% CI 1.6-4.8)], requirement of oxygen [OR 17.8 (95% CI 4.0-80.3)], positive pressure support [OR 3.7 (95% CI 1.2-10.5)] and shock requiring inotropes [OR 3.0 (95% CI 1.3-6.7)] was significantly higher in scrub typhus group as compared to the non-scrub typhus group (Table 1). Pediatric scrub typhus who were hospitalized had severe systemic manifestations when compared to other causes of fever.

Mevalonate kinase deficiency syndrome: Single center experience

The aimof this study was to analyze the clinical, laboratory and molecular genetic data of 26 patients (15 boys, 11 girls) diagnosed with mevalonate kinase deficiency syndrome (MKD).Subjects and methods. The age of MKD manifestation ranged from 0 to 30.0 months (M – 1.5 months). Clinical manifestations and their severity were extremely diverse: from symptoms resembling Marshall’s syndrome to severe systemic manifestations with respiratory failure, hepatosplenomegaly and pancytopenia.Results/Conclusion. All patients had homozygous/compound-heterozygous mutations in theMVKgene, including 10 newly described variants. In all 20 patients, who have been treated with IL-1 inhibitors long enough to assess the effect of the treatment, drastic improvement of the condition was noted, but only in 17/20 patients achieved full remission.