Internal Organ Involvement Research Articles

The Prospects of Phytomedicines and Nanomedicines to Treat Leishmaniasis: A Comprehensive Review.

The global shift in lifestyle has prompted health agencies to redirect their focus from poverty-related diseases to the emergence of lifestyle diseases prevalent in privileged regions. As a result, these diseases have been labeled as "neglected diseases," receiving limited research attention, funding, and resources. Neglected Tropical Diseases (NTDs) encompass a diverse group of vector-borne protozoal diseases that are prevalent in tropical areas worldwide. Among these NTDs is leishmaniasis, a disease that affects populations globally and manifests as skin abnormalities, internal organ involvement, and mucous-related abnormalities. Due to the lack of effective and safe medicines and vaccines, it is crucial to explore alternative resources. Phytomedicine, which comprises therapeutic herbal constituents with anti-leishmanial properties, holds promise but is limited by its poor physicochemical properties. The emerging field of nanomedicine has shown remarkable potential in revitalizing the anti-leishmanial efficacy of these phytoconstituents. In this investigation, we aim to highlight and discuss key plant constituents in combination with nanotechnology that have been explored in the fight against leishmaniasis.

Drug reaction with eosinophilia and systemic symptoms: Analysis of cutaneous phenotype as a prognosis factor

Study objectiveThe DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a severe and potentially fatal toxidermia due to various visceral involvements. Identifying factors predisposing to serious complications is essential for clinical and therapeutic management. This study aims to analyze the cutaneous presentation of DRESS and its role as a prognostic factor. Patients and methodsThis is a retrospective, descriptive, and analytical study conducted over nine years at the dermatology department in Fes, including all hospitalized DRESS cases. ResultsThe maculopapular rash was the most frequent phenotype (49.3%), followed by erythroderma, morbilliform exanthem, and polymorphous erythema-like rash. In all, 52.8% of patients had renal involvement and 45.8% had hepatic involvement, while 81.9% exhibited hypereosinophilia. The maculopapular rash and erythroderma were more associated with internal organ involvement, although no significant statistical correlation could be demonstrated. Allopurinol was the most implicated drug in 51.4% of the cases. No correlation was found between the type of medication and the cutaneous presentation. In all, 8.3% of the patients died, primarily those with erythroderma (15.8%). ConclusionOur study demonstrated that maculopapular rash and erythroderma are the most common presentations and are most associated with internal organ complications, with a more unfavorable prognosis for erythrodermic cases.

Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis

ObjectivePatients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival.MethodsPatients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis.ResultsOf 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations.ConclusionWe found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials.

Klippel-Trénaunay-Weber Syndrome: Prenatal Diagnosis and Review of the Literature.

Klippel-Trénaunay-Weber syndrome (KTW) is a rare congenital disease, representing a challenge in prenatal diagnosis due to overlapping characteristics with other syndromes and no specific genetic markers known to date. We have collected all the cases present in the literature on the prenatal diagnosis of KTW, emphasizing common ultrasound findings that can guide the clinician and genetics to the prenatal counseling. Thus, we collected all the information about the postnatal prognosis and the necessity for treatment. Our review of 44 cases highlights the typical common features: hemihypertrophy, predominantly affecting the right leg, with cystic lesions extending to the trunk or upper limbs and rare internal organ involvement. Prenatal complications, including hydrops and polyhydramnios, emphasize the need for a careful ultrasound follow-up. Despite no identified genetic mutation, genetic counseling and invasive testing are recommended. Mortality rate due to a severe complication known as Kasabach-Merritt syndrome, underlines the importance of early diagnosis and accurate management strategies. Prenatal diagnosis of KTW, guided by ultrasound findings and genetic counseling, could help with informed decision-making and optimal care planning.

Pharmacoeconomic analysis of rituximab and belimumab therapy in patients with systemic lupus erythematosus

The progressive course of systemic lupus erythematosus (SLE) with high activity and severe internal organs involvement requires the prescription of expensive biologic disease-modifying antirheumatic drugs (bDMARDs), rituximab (RTM) and belimumab (BLM), whose comparative clinical and economic efficacy has not been adequately studied.Objective: to evaluate the clinical and economic efficacy of RTM and BLM therapy in patients with SLE.Material and methods. The study included 50 SLE patients who were divided into two groups and received RTM (group 1, n=25) or BLM (group 2, n=25) therapy for 12 months. The clinical and economic analysis was performed with the cost-effectiveness method using the cost-per-responder (CPR) model. A clinically significant improvement in SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index modified 2K; Δ ≥4) was considered a response to therapy. Direct and indirect costs were considered in the analysis.Results and discussion. Against a background of therapy, there was a decrease in SLE activity with a decrease in median SLEDAI-2K in group 1 from 12 [10.5; 18] to 8 [4; 10] and in group 2 from 10 [8; 14.5] to 4 [2; 4] (p< 0.001 in both cases). A clinically significant improvement was observed in 56% of patients in group 1 and 72% of patients in group 2. The peculiarities of the BLM dosing regimen caused higher (1.7 times) total costs than in the case of RTM. According to the CPR value, RTM showed a greater benefit (1.3 times) than BLM (954 thousand rubles versus 1.25 million rubles). The incremental cost-effectiveness ratio (ICER) was 1.4 million rubles, which does not exceed the threshold of willingness to pay for a domestic patient.Conclusion. When comparing BLM and RTM therapy for SLE patients in real-life clinical practice, greater clinical and economic efficiency was demonstrated for RTM. BLM therapy was found to be “cost-effective”.

Diving deep into lupus: Gastrointestinal involvement insights from the Oman lupus study.

This multicenter longitudinal study investigated the prevalence of gastrointestinal (GI) manifestations in lupus patients and determined the risk factors associated with mortality. This study is part of the Oman Lupus Study, which included 1160 patients who met the classification criteria for systemic lupus erythematosus (SLE) from January 2006 to February 2020. All patients were screened for GI symptoms and involvement. We identified 91 patients with GI manifestations, with a prevalence rate of 8.53% in the pediatric group and 7.75% in the adult group, and this difference was not statistically significant (p = .755). Ischemic colitis was significantly associated with longer disease duration (p < .001) and positivity for B2-glycoprotein I (B2GPI) autoantibodies (p < .0001). Moreover, a significant correlation was found between ischemic colitis and hematologic manifestations (p = .001), lupus nephritis (p = .007), pulmonary complications (p = .000-.039), and some cardiac complications (p = .012-.269). Mortality rates were greater in patients with GI involvement (24.37%), including those with ischemic colitis (p = .005), chronic peritonitis (p < .001), and spleen/liver infarction (p = .001). Sepsis, thrombocytopenia, and different internal organ involvement rates were significantly associated with increased mortality. This research provides significant insights into GI manifestations in lupus patients. A higher mortality rate was found to be associated with organ involvement, disease duration, autoantibody profile, and specific complications. Considering this fact, it is vital to prioritize management strategies to improve clinical outcomes in this group of patients.

Systemic sclerosis: one year in review 2024.

Systemic sclerosis (SSc) is a rare and chronic connective tissue disease of unknown aetiology and characterised by three main pathogenetic events represented by endothelial damage, inflammation with activation of the immune system leading to production of specific autoantibodies and finally fibrosis. SSc is a heterogeneous disease and the classification in two subsets, the limited cutaneous (lcSSc) subset and the diffuse cutaneous one (dcSSc), is not capable of capturing the broad and different phenotypic expression of the disease. In the last years progress has been made in the knowledge of SSc pathogenesis, in its early diagnosis and new therapeutic strategies have been proposed, however, the management of SSc still represents a challenge for the clinician. For this reason, every year several studies investigate new insights of disease pathogenesis, internal organ involvement and therapeutic approaches. The purpose of this review is to provide an overview of the literature published in 2023.

Multimorbid pathology at psoriasis (scientific review)

Chronic auto-inflammatory process in psoriasis is associated with the involvement of internal organs and systems, as well as the development of several systemic disorders: heart failure, psoriatic arthritis, diabetes, obesity, etc. In this regard, the purpose of our study is to integrate information about comorbid and concomitant pathology in patients with psoriasis. Data on the biological aspects of the increased risk of occurrence and adverse cardiovascular outcome of myocardial infarction, stroke and cardiovascular mortality in patients with psoriasis are supported by clinical observations on the relationship of the course of coronary heart disease with the area of skin lesion. The association between the presence of obesity and an increased level of proinflammatory cytokines has been confirmed, which may be one of the triggers for the development of psoriatic arthritis associated with early disability of patients with psoriasis. There was a greater incidence of non-response to psoriasis treatment among obese patients. Cardiovascular complications are the most common cause of death for patients with psoriasis. Identifying common combinations of comorbid and concomitant diseases in the main chronic disease can serve as a basis for the development of tactics and criteria for patient management in order to optimize treatment.

Assessment of Skin by High Frequency Musculoskeletal Ultrasound in Egyptian Patients with Systemic Sclerosis

Abstract Background Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis (SSc). The extent of skin involvement is associated with internal organ involvement with severe disease course and poor prognosis. SSc skin involvement is characterized by three phases in temporal sequence: edematous, fibrotic, and atrophic. A palpation-based semi- quantitative score, the modified Rodnan skin score (mRSS) is widely used for the assessment of skin involvement. It is a quick, noninvasive clinical assessment that correlates with histological grading of skin fibrosis. However, it lacks the sensitivity to differentiate between clinically indistinguishable pathological phases such as inflammatory edema vs. established fibrosis. More objective approaches to measure skin involvement imaging have been developed in the past decades.In our study, we review the use of ultrasound for the assessment of early changes in skin thickness and echogenicity in patients with SSc, focusing. mainly on high frequency ultrasound. Aim of the Work to evaluate the role of high frequency ultrasound (HFUS) of skin in assessment of early changes in skin thickness and echogenicity in patients with SSc. Patients and Methods Our study is a cross-sectional, observational study involving homogenous groups consisting of 23 SSc patients and 21 healthy age and sex matched controls. Patients who fulfilled the 2013 ACR/EULAR Classification Criteria for SSc. Results DT was evaluated by both mRSS and HFUS at 5 skin areas in both patients and control. We found statistically significant difference between the two studied groups as regards in area 1 longitudinal (P = 0.017) and area 1 in transverse (P = 0.038), tendency to significance in area 2 (P = 0.054). Subclinical dermal involvement was detected by HFUS even in the skin areas in patients who had a normal local MRSS ( These areas were not planned to be assessed by high frequency ultrasound but added to the five areas to be assessed to evaluate for ultrasound detected subclinical involvement of skin in SSc patients ). In particular, DT was highly significantly greater in patients with area with Rodnan zero score at dorsum of hand than in healthy subjects (longitudinal and transverse) (P &amp;lt; 0.001, 0.005 ) respectively. Similar changes at the level of echogenicity occurred in determination of the stage of the disease, with increased skin thickness and decreased echogenicity occurring early and during skin disease activity due to edema; and decrease skin thickness and increased echogenicity occurring late with skin atrophy Conclusion that high frequency ultrasound is a useful tool in assessment of skin pathologic changes (even subclinical changes) in terms of thickness and echogenicity in patients with SSc both at disease onset and during follow up of response to therapy and disease stage. Moreover, it could be a useful screening tool with definite cutoff values at certain areas that differentiate normal from pathologic skin thickness.

Late-age onset systemic sclerosis—clinical and serological characteristics

The clinical course and serological profile of the late-age onset systemic sclerosis (LAO SSc) and the early-age onset SSc (EAO SSc) was compared. The study enrolled 157 patients that fulfilled the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria for systemic sclerosis (SSc). Among them, 69 had diffuse cutaneous SSc (dcSSc) and 88 limited cutaneous SSc (lcSSc). Within this population, 39 patients developed the disease over the age of 60 years old (LAO SSc) and 118 prior to that age (EAO SSc). The subtype of SSc, the incidence of internal organ involvement, the prevalence of malignancy, mortality, and serological profile were compared between both groups. The LAO SSc was observed in 39 of total 157 patients with SSc and exhibited a notably higher prevalence of pulmonary arterial hypertension (p = 0.014), heart involvement (p = 0.0014), and renal involvement (p = 0.0002). The occurrence of arthralgias was less common in the LAO SSc group (p = 0.02) than in the EAO SSc group. Furthermore, in the LAO SSc group, the prevalence of anti –RNA polymerase III antibodies (p = 0.008) and antiPM/Scl antibodies (p = 0.048) were significantly lower than in the EAO SSc group. On the other hand, higher anti-Th/To antibody levels (p = 0.014) were recorded in the LAO SSc group. Approximately 25% of SSc patients experienced a delayed onset of the disease after the age of 60 years old. Some clinical and serological features of late-onset SSc were markedly different from that in early-onset disease. Particularly noteworthy is the fact that involvement of internal organs such as heart and kidneys, as well as pulmonary arterial hypertension were much more often observed among patients with LAO SSc which in our suggestion may be referred to age-related co-morbidities.Key Points• Significant differences in clinical and serological profile of the disease were found between late-age onset (LAO) and early-age onset (EAO) SSc.• Incidence of dcSSc as well as prevalence of anti–RNA polymerase III and anti-PM/Scl antibodies were found to be lower in patients over 60 years old compared to those before 60, but regardless of the age of the disease onset.• Internal organ morbidity, notably pulmonary arterial hypertension, renal impairment and heart disease were significantly more common in elder SSc patients as well as in those with late disease onset.• These findings may suggest an impact of age-related co-morbidities on the course of late-age onset SSc.

Systemic sclerosis sine scleroderma is more aggressive in children than in adults.

To compare the clinical and laboratory features of paediatric SSc sine scleroderma (ssJSSc) with adult-onset ssSSc. Demographic, clinical and laboratory data of ssJSSc, retrospectively retrieved from our hospital medical records, case reports from the literature and from the Pediatric Rheumatology European Society JSSc registry, were compared with the Padua cohort of adult patients with ssSSc. Patients were defined as having ssSSc if they never had skin involvement but all the following features: (i) RP and/or digital vasculopathy, (ii) positive ANA, (iii) internal organs involvement typical of scleroderma and (iv) no other defined CTD. Eighteen juvenile and 38 adult-onset ssSSc patients, mean disease duration 5.8 and 9.7 years, respectively, entered the study. The frequency of females affected was significantly lower in ssJSSc (38.9% vs 89.5%, P < 0.0001). When compared with adults, ssJSSc displayed fewer SSc-specific capillaroscopy abnormalities (68.8% vs 94.7%, P = 0.02) while having significantly higher vascular (digital pitting scars, ulcers 35.3% vs 10.5%, P = 0.042), respiratory (50.0% vs 23.7%, P = 0.02) and cardiac (50.0% vs 2.6%, P < 0.0001) involvement. The outcome was significantly worse in ssJSSc as six patients (33%) died (n = 3) or reached an end-stage organ failure (n = 3) in comparison with only two deaths (5.3%) in the adult cohort. ACA were significantly lower in children (20.0% vs 68.4%, P = 0.001) while no difference was noted for other SSc-specific autoantibodies. Compared with adults where ssSSc generally has an indolent course, children present with aggressive disease that heralds a worse prognosis characterized by high cardiorespiratory morbidity and mortality.

Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients

Anti-topoisomerase-I antibody (ATA) is associated with disease severity and internal organ involvement in patients with systemic sclerosis (SSc). The correlation between ATA levels and the clinical course of SSc is unclear. We aimed to determine the correlation between ATA level and survival time and the onset of internal organ fibrosis in SSc patients. This historical cohort study was conducted in adult SSc patients with quantitative tests of ATA between January 2019 and December 2022. Patients with overlap syndrome and no quantitative ATA test were excluded. According to the sample size calculation, and 10% compensated for missing data, a total of 153 patients were needed. The respective mean age on the study date and median ATA level was 59.9 ± 11.3 years and 370 U/mL (range 195–652). Most cases (107 cases; 69.9%) were the diffuse cutaneous SSc subset. According to a multivariable analysis, the ATA titer had a negative correlation with the onset of cardiac involvement (Rho − 0.47, p = 0.01), and had a positive correlation with skin thickness progression (Rho 0.39, p = 0.04). Eleven cases exhibited ATA levels < 7 U/mL and outlier ATA levels were excluded, 142 cases were included in the sensitivity analysis, and multivariable analysis showed the correlation between early onset of ILD and cardiac involvement (Rho − 0.43, p = 0.03 and Rho − 0.51, p = 0.01, respectively). The ATA level was correlated with neither the survival time nor the onset of renal crisis in both analyses. High ATA levels were correlated with a short onset of ILD and cardiac involvement and the presence of extensive skin tightness. Quantitative tests of ATA could serve as an effective tool for identifying patients at risk of an unfavorable prognosis.

P156 Type I interferon is raised across connective tissue diseases and is associated with haematological abnormalities and specific autoantibody profiles

Abstract Background/Aims The overlapping clinical and serological features among connective tissue diseases (CTDs) suggest a shared molecular aetiology. A molecular taxonomy of CTDs offers new opportunities in clinical trial design, which can potentially be translated into targeted treatment. In a previous study of 164 patients, we identified a type I interferon (IFN) positive subgroup within an unselected CTD cohort associated with specific clinical and serological features. Here, we aim to investigate the relationship between type I IFN and the clinical and immunological phenotype in a larger CTD cohort and determine whether a distinct subpopulation of patients can be identified. Methods Adult patients with at least 1 CTD clinical feature and CTD-related autoantibody were recruited from five rheumatology centres in North West England into the Lupus Extended Autoimmune Phenotype (LEAP) cohort. A 24-gene interferon-stimulated gene (ISG) score was calculated using NanoString as described by Neasens et al. 2022. Results Most patients had lupus (36%). 160 of 344 (46.5%) patients had a positive ISG score across all CTDs with 64/125 (51%) of lupus patients (Fig.1). Patients with positive ISG score were younger and had longer disease duration (p &amp;lt; 0.005 for both). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had significantly increased frequency of specific autoantibodies (anti-Smith, anti-Chromatin, anti-RNP, anti-Ro) and Rheumatoid Factor, and haematological abnormalities (lower haemoglobin, and lower total white cell and neutrophil counts) in an adjusted model including the CTD subtype. Conclusion In CTD patients, IFN type I positivity was identified across a subset of patients of all CTDs and is associated with specific autoantibodies and haematological parameters; these results support the findings of our previous smaller study. The identification of an IFN I-positive subgroup within an unselected CTD regardless of clinical diagnosis supports a molecular-based approach to treatment. Disclosure A. Madenidou: Grants/research support; Janssen and UCB. G.I. Rice: None. S. Dyball: Grants/research support; UCB, Novartis,Eli Lilly. B. Parker: Honoraria; Fresenius-Kabi and AbbVie. Member of speakers’ bureau; Eli Lilly and Roche. Grants/research support; Genzyme/Sanofi and GlaxoSmithKline. T.A. Briggs: Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Member of speakers’ bureau; AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Novartis, Janssen and UCB.

Pulmonary function in Thai patients with systemic sclerosis; a single center 6-year retrospective study

Background Interstitial lung fibrosis is a major cause of internal organ involvement and the leading cause of death in patients with systemic sclerosis (SSc). This study aimed to demonstrate the characteristics of pulmonary function (PF) in Thai patients with SSc and the association between PF and body mass index (BMI) and anti-topoisomerase (anti-Scl70). Methods All patients diagnosed with SSc in our tertiary care teaching hospital database between 2016 and 2021 were reviewed. Clinical characteristics and PF were recorded and analyzed. Results Of 211 SSc patients, 128 patients who underwent the PF test were enrolled; 102 (79.7%) were female. The mean (SD) age was 54.0 (12.5) years. The mean (SD) forced expiratory volume in one second (FEV1) forced vital capacity (FVC) ratio was 0.8 (0.1). The mean (SD) % predicted values of FEV1, FVC, and diffusing capacity of the lungs for carbon monoxide (DLCO) were 76.3 (16.3), 69.1 (15.8), and 75.5 (22.8), respectively. A restrictive spirometry pattern (RSP), defined as FVC &lt; 80% predicted, was found in 78.8% of the patients. DLCO had a moderate positive linear correlation with FVC (r=0.50, p &lt;0.001) and a moderate negative linear correlation with BMI (r=-0.36, p &lt;0.001). However, there was no correlation between FVC and BMI. There was no statistical difference in demographic data or the presence of anti-Scl70 among patients with or without RSP. Conclusions RSP is common among Thai patients with SSc. Spirometry is a cost-effective screening tool for detecting SSc-related pulmonary involvement in resource-limited settings. However, the power of using demographic data and the presence of anti-Scl70 to determine the probability of pulmonary complications remains limited.

Atypical Rare Presentations of Cutaneous Tuberculosis: A Report of Two Cases

Cutaneous tuberculosis (TB) is the result of a chronic infection by Mycobacterium TB. The clinical manifestations are variable and depend on the interaction of several factors. TB and malignancy present global threats claiming millions of lives and inflicting formidable suffering worldwide. We present two cases of atypical, rare presentations of cutaneous TB. Cases of concurrent scrofuloderma and lupus vulgaris (LV) with miliary tuberculosis of the lung and cutaneous tuberculosis; atypical presentation of LV with concurrent HIV in a 10 year old child. Concurrent presentation of cutaneous TB with internal organ involvement is a rare entity in an immunocompetent asymptomatic individual like our patient. HIV coinfection with cutaneous TB has not been described in any of the childhood series published from India and ours is probably the first report of its kind. It is imperative that physicians have a high index of suspicion to quickly and effectively diagnose and treat these substantially morbid skin conditions.

S2k guideline: Diagnosis and therapy of localized scleroderma.

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoSrepresents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoScan be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.

An observed repeat case of drug reaction with eosinophilia and systemic symptoms syndrome with modified anti-tuberculosis therapy: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, while uncommon, presents a potentially hazardous condition. It is a drug-induced multi‑system immunological hypersensitivity reaction, characterized by the triad of fever, rash, and internal organ involvement. This is a case report of a 60-year-old Indian female who developed a repeat episode of DRESS syndrome following modified anti-tuberculosis therapy (ATT). She had a past history of DRESS syndrome caused by first-line antitubercular drugs. This case report aims to highlight the challenges in managing DRESS syndrome in the context of tuberculosis (TB) treatment, as well as to emphasize the importance of prompt withdrawal of the culprit drugs and immediate initiation of appropriate supportive care. This case report also highlights the high risk of recurrence of DRESS syndrome following the re-administration of the offending medication, especially antitubercular drugs.

Inflammatory and neutrophil activation markers in Behcet's disease

Behcet's disease (BD) is a systemic vasculitis characterized by recurrent episodes of inflammation with aphthous stomatitis, genital ulcers, skin, joint and internal organ involvement. Currently, there are no reliable laboratory markers that can be used to monitor BD activity. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have low sensitivity, so the search for new biomarkers continues. Neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), immature granulocytes (IG), neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII) are new inflammatory indicators whose role in BD is not well studied.Objective: to evaluate and compare the efficacy of the determination of NEUT-RI, NEUT-GI, IG, SII, NLR, ESR and CRP in the diagnosis of active BD.Material and methods. 84 patients with a reliable diagnosis of BD and 38 healthy controls were included in the study. BD activity was assessed using the Behcet’s Disease Current Activity Form (BDCAF). Patients with BD were divided into two groups according to activity: Group I included 41 patients with high activity (BDCAF &gt;5) and Group II included 43 patients with low activity (BDCAF ≤5). A complete blood count with determination of NEUT-RI, NEUT-GI, IG, SII and NLR was performed in all patients and healthy donors using the Sysmex XN 1000 automated haematology analyzer (Sysmex Сorp, Japan). ESR was determined using the Westergren method. High-sensitivity serum CRP level was determined in all patients with BD (normal range ≤5) by immunonephelometric method.Results and discussion. Patients with active BD had significantly higher levels of neutrophils, SII, NLR, NEUT-RI, IG, ESR and CRP compared to patients with low disease activity. ROC analysis was performed to compare the significance of these inflammatory markers in the assessment of BD activity. The SII had the largest area under the ROC curve (AUC =0.816). The sensitivity and specificity of the SII at a value of 509.75 or higher for determining the active form of BD were 79.4% and 71.8%, respectively.Conclusion. The new inflammatory parameters (SII, NLR, NEUT-RI and IG) and the traditional inflammatory parameters (ESR, CRP, neutrophils) can serve as laboratory markers for BD activity. SII is the most informative parameter to determine BD activity with optimal sensitivity and specificity.

Localized scleroderma

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises aheterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. Adistinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. Adetailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with aprominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

Pigmentary Changes in Systemic Sclerosis are Associated with More Severe Cutaneous Sclerosis and Severity of Other Systems: A Cross-sectional Study from India.

Pigmentary changes of the skin in systemic sclerosis in the form of diffuse hyperpigmentation and salt-and-pepper pigmentation are well documented in the literature; however, its association with disease severity and extent of underlying internal organ involvement has not been well studied. To assess the correlation between morphology and extent of pigmentary changes with the degree of cutaneous sclerosis and frequency and degree of major organ involvement. This was a cross-sectional descriptive study conducted in a tertiary care teaching hospital from December 2014 to November 2016. Consecutive patients of systemic sclerosis attending the outpatient department were screened, and patients satisfying the diagnosis as per the American Rheumatism Association criteria were recruited. Skin sclerosis was quantified using modified Rodnan skin score (MRSS), whereas pigmentary changes were calculated in terms of percentage of body surface area involved by rule-of-nine method. Investigations were carried out depending on organ involvement and as per respective specialty consultations with focus on pulmonary, cardiac, and gastrointestinal systems. Of the 50 patients recruited, all had cutaneous involvement in the form of binding down of skin, followed by pigmentary changes. MRSS was significantly higher in patients with any pigmentary alteration (P = 0.03) compared to those without any pigmentary changes. There was a rising trend in between the MRSS severity and the proportion of patients with hyperpigmentation, and it was statistically significant (P = 0.04). Among systemic involvement, lung was involved in the form of interstitial lung disease in 94% patients (n = 47). However, skin pigmentation of any type was associated with lower high-resolution computed tomography scores (P = 0.02). This study shows that in systemic sclerosis patients presenting with pigmentary skin manifestations, cutaneous sclerosis is significantly higher.