Interstitial lung disease in patients with connective tissue disease: Subtypes, clinical features and comorbidities in the Western Cape, South Africa.

Background: Interstitial lung disease (ILD) is highly prevalent in patients with connective tissue disease (CTD) and is poorly characterised in South Africa. Objectives: To describe the clinical, serological and radiological features of CTD-ILD and their associations in patients attending a tertiary referral hospital. Methods: A cross-sectional study collating clinical, serological and radiological features of CTD-ILD in patients attending rheumatology and respiratory outpatient clinics in a tertiary referral hospital. Results: Of 124 CTD-ILD patients, 37 (29.8%) had rheumatoid arthritis (RA), 32 (25.8%) systemic sclerosis (SSc) and 55 (44.4%) other autoimmune connective tissue diseases (OCTD). Most patients were female (86.3%), of mixed racial ancestry (75.0%), and the median age was 55 years. Nonspecific interstitial pneumonia (NSIP) was the most common ILD pattern (63.7%), followed by usual interstitial pneumonia (UIP) (26.6%). Overall, 60.5% were current or past smokers, 33.1% had previous pulmonary tuberculosis infection, and 75.6% had gastro-oesophageal reflux disease. Patients with RA were older, had similar frequencies of NSIP and UIP, and had significantly better pulmonary function tests than the SSc and OCTD groups. Within three years of CTD diagnosis, two-thirds of the SSc and OCTD patients and almost half of the RA patients had developed ILD. Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT). No case of acute pneumonitis was documented in CTD-ILD patients treated with methotrexate (MTX). Conclusion: We suggest routine HRCT in all newly diagnosed CTD patients, particularly those with SSc and OCTD, where more than two-thirds of the patients had developed ILD within three years of their CTD. The use of MTX was not associated with the development of acute pneumonitis in patients with ILD. Key points: Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT).Smoking, environmental toxins, gastro-oesophogeal reflux and previous pulmonary tuberculosis infection were significant comorbidities in CTD-ILD patients.Early screening of ILD with HRCT is recommended, particularly in SSc.Use of MTX before and after ILD diagnosis was not associated with acute pneumonitis.

New life after near death: Surviving critical COVID-19 infection.

Background: Few studies have explored the illness perceptions, experiences or attitudes towards the future of survivors of critical coronavirus disease 2019 (COVID-19). Through in-depth qualitative interviews, we aimed to enrich our understanding of participants' perspectives, with the hope of offering more holistic and appropriate care to future patients. Methods: Participants who had survived critical COVID-19 illness (defined as a laboratory or clinical diagnosis of COVID-19, with hypoxia requiring high-flow nasal oxygen (HFNO) or mechanical ventilation) were invited to participate. After informed consent procedures, clinic-demographic details were documented and individual interviews conducted using a topic guide, and were audio-recorded, translated, transcribed and coded into NVivo software where themes were extracted. Results: Of 21 participants (13 female, 8 male), the mean age was 51.8 years (range 34 - 68), and mean duration of COVID symptoms was 21.7 days (range 17 - 37). Eighteen participants had been on HFNO, and 5 required mechanical ventilation. The major themes were: distressing experience; faith-based beliefs sustaining them; gratitude to healthcare workers (HCWs); better understanding of COVID and how dangerous it is; optimism for the future; and a resolve to implement lifestyle changes. Conclusion: Qualitative interviews revealed our participants' experience of severe COVID-19 as a difficult and terrifying ordeal, mitigated by faith-based beliefs, and the presence and care of HCWs. These experiences were reported by the participants as life changing, and all were inspired to focus on future self-care, and invest in fulfilling relationships. These insights call for future interventions to improve patient-centred care, including follow-up debriefing sessions, and support for lifestyle changes.

'The feeling of not being entitled to something': fertility, pregnancy, and sexuality among women with systemic lupus erythematosus in South Africa.

Objective: Fertility, pregnancy, and the postpartum period can pose many challenges for patients with systemic lupus erythematosus (SLE) in sub-Saharan Africa. We explored the perceptions and experiences of South African women relating to fertility and pregnancy.Method: In-depth interviews were conducted with 25 consenting women with SLE. We explored their perceptions and experiences on conception, pregnancy, and sexuality. Data were analysed using Nvivo software.Results: Participants had a mean age of 30.9 years (range 22-45 years) and mean disease duration of 4.5 years (range 1-5 years). The majority were black Africans, and the remainder were of mixed racial ancestry. Unemployment, low educational level, and singlehood status were the most predominant sociodemographic features. Most participants had been pregnant and a few reported being sexually inactive. Participants described many negative pregnancy outcomes including lupus flares, miscarriages, premature deliveries, prolonged hospitalization, and unexpected caesarean sections. Conflicting medical advice on conception, together with conflicting personal, cultural, and societal pressures to procreate, resulted in emotional turmoil and pessimism. Participants frequently described intimacy problems, loss of libido, and infidelity by partners leading to sexually transmitted infections. Aesthetic and physical concerns were perceived as the main causes of infidelity. Most participants felt confined to these relationships as they were financially dependent on their partners, which added to their stress.Conclusion: A combination of patient-centred care focusing on safe, effective contraception and medication targeting remission state, constant counselling, consistent information, and a pregnancy managed jointly by an obstetrics and rheumatology team could achieve optimum results.

Living with systemic lupus erythematosus in South Africa: a bitter pill to swallow.

BACKGROUND: Systemic lupus erythematosus (SLE) often has a profound negative impact on health-related quality of life (HRQoL). In the absence of any qualitative studies in sub-Saharan Africa, we undertook a study to explore living experiences, perceptions and unmet needs of South African patients with SLE. METHODS: Twenty-five women with SLE consented to participate in the study. They underwent individual in-depth interviews exploring their physical concerns, emotional health, sexual well-being and fertility. NVivo software was used for analysis. RESULTS: Participants were either of black ancestry or mixed racial ancestry, mainly indigent with only a quarter gainfully employed. Living with pain was the most common complaint, negatively impacting on activities of daily living (ADL), family expectations, social life, sleep and intimacy. Most participants expressed challenges of living with fatigue, and many felt their fatigue was misconstrued as being 'simply lazy'. This pernicious fatigue had negative consequences on many facets of ADL, including caring for dependants, job sustainability and sexual well-being. All participants experienced low emotional states, often associated with suicidal ideations. Many experienced difficulties with fertility and childbearing and these were exacerbated in many instances by the pessimism of health care providers, resulting in confusion and depression. Physical disfigurements resulting from lupus-associated alopecia and rashes and corticosteroid-induced weight fluctuations were a major concern. These changes often affected self-image and libido, leading to strained personal relationships. Coping mechanisms that participants adopted included intense spiritual beliefs, 'pushing through the difficult times' and use of alternative therapies to relief symptoms was common. A poor understanding of SLE on the part of participant's family and the community, coupled with the unpredictable course of the disease, exacerbated frustration and social exclusion. For most, limited income, lack of basic services, family dependencies, and comorbid diseases, such as human immune deficiency virus (HIV), exacerbated the daily negative SLE experiences. CONCLUSION: In this study of mainly indigent South African women, SLE is associated with complex, chronic and challenging life experiences. The chronic relapsing and unpredictable nature of the disease, poor understanding and acceptance of SLE, compounded by a background of poverty, inadequate social support structures, negatively impact on a range of personal, social and vocational daily life experiences. Improved access to psychosocial services and SLE education might result in better outcomes. TRIAL REGISTRATION: (Ethics Project identification code: 275/2016 and M160633 registered 10 & 29 August 2016).

Mutations of FAM111B gene are not associated with Systemic Sclerosis.

Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (FAM111B) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established FAM111B as a candidate gene for SSc. PATIENTS AND METHODS: Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in FAM111B. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B. RESULTS: Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two FAM111B genetic variants. The c.917 A > G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988 C > T variant (rs35732637) occurred in three SSc patients and 42/243 (17.3%) of healthy controls, and is a known polymorphism. CONCLUSION: One rare variant was found in a patient with SSc but has no functional or structural impact on the FAM111B gene. In this cohort, FAM111B gene mutations are not associated with SSc.

Living with systemic lupus erythematosus in the developing world.

Most of our understanding of SLE and its negative impact originates from developed countries. This review aims to collate existing literature on Health-Related Quality of Life (HRQoL) in SLE patients living in developing countries to identify the gaps for the focus of future research. A narrative literature review was compiled using selected MeSH terms to search EBSCOHOST for articles published between January 1975 and February 2018 pertaining to HRQoL in SLE patients in developing countries. 31 studies from 11 countries were included for analysis. Only one longitudinal, one randomized controlled trial (RCT), one qualitative study, and two intervention studies were found. High disease activity and organ damage were associated with poor functional ability, mental health and low socio-economic status (SES). Poor SES is a recurring theme in developing countries, and worsens all SLE outcomes by reducing access to healthcare, mental, social and emotional support systems. In developing countries, SLE has a globally negative impact on patients' HRQoL, similar to that seen in developed countries. There is an urgent need for more HRQoL studies, and in particular, longitudinal, qualitative and interventional studies in these countries to investigate unmet needs, and to explore novel strategies to improve patient outcomes.

HIV Infection and Osteoarticular Tuberculosis: Strange Bedfellows.

We report the case of a 47-year-old female patient with rheumatoid arthritis and HIV infection presenting with a 3-week history of a painful swollen knee, increased serum inflammatory markers, and a low CD4 lymphocyte count. The diagnosis of TB arthritis was made by synovial fluid culture, GeneXpert/PCR, and confirmed by histopathology of a synovial biopsy. A mini literature review suggests that although HIV infection is associated with extrapulmonary TB, osteoarticular TB is a relatively unusual presentation in an HIV positive patient. The diagnostic utility of the GeneXpert test is explored. We also describe the patient's good response to an intra-articular corticosteroid injection in combination with standard anti-TB therapy.

Inflammatory arthritis in HIV positive patients: A practical guide.

BACKGROUND: Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. METHODS: We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. RESULTS: There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. CONCLUSIONS: This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients.

Standard of treatment and outcomes of adults with lupus nephritis in Africa: a systematic review.

BACKGROUND: Lupus nephritis (LN) is a significant cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE) and the severity of disease has been described to be increased in Africans. Observational studies have been conducted; however, the treatment and outcome of African patients with LN has not been rigorously assessed. METHODS: We conducted a systematic review of studies selected from a PubMed search of outcome in Africans with biopsy-proven LN from 1 January 1990 to 30 June 2015. Studies that gave information on histology, treatment and outcome of patients were included. RESULTS: Sixteen studies were selected from a search that yielded 302 papers; half were from North Africa, 2/16 (12.5%) were prospective studies and 2/16 (12.5%) were multi-centre studies. The sample size of reported biopsies in the studies ranged from 22 to 246 patients. Only 3/16 (18.8%) studies used more recent criteria for the classification and reporting of renal histology, and proliferative LN (class III and IV) were reported with increased frequency from the studies. For induction therapy, all the studies reported use of corticosteroids while 15/16 (93.8%) of the studies also used cyclophosphamide (CYC) as an induction agent. Overall mortality rates ranged from 7.9% to 34.9% with increased disease activity, kidney failure and infections cited as common causes of mortality. Five-year renal survival was 48-84% while five-year patient survival was 54%-94%. Survival rates were higher for studies reported from North Africa. CONCLUSION: This analysis highlights diagnostic challenges in LN in Africa and shows that a CYC/glucocorticoid-based regimen remains the standard of treatment for adult patients. The contributions of this therapy to reported outcomes of LN in Africa require further exploration.

The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

BACKGROUND: The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. OBJECTIVE: The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. METHODS: Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. CONCLUSION: Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies.

Evidence-based treatment of systemic lupus erythematosus and its complications.

Outcomes for patients with systemic lupus erythematosus (SLE) have improved during the last two decades as our understanding of the disease expands. In particular, the importance of antimalarial therapy for addressing and preventing a host of complications in SLE has emerged. Furthermore, evidence is mounting that corticosteroids, while offering excellent control of disease activity, are responsible for many of the late complications of SLE and need to be prescribed in modest doses for the shortest time possible. To achieve this, an understanding of the available 'steroid-sparing' immunosuppressants is useful. Specific attention needs to be paid to the two most important complications of SLE, i.e. infections and atherosclerotic cardiovascular events. Awareness of, screening for and aggressive management of risk factors for these comorbidities are paramount.

Lupus in Africa: can we dispel the myths and face the challenges?

The epidemiology of systemic lupus erythematosus (SLE) in Africa is largely undetermined, and the perception persists that the incidence of SLE on the continent is very low. Recent studies as well as our own experience, however, suggest that this is not the case. We have conducted a survey amongst medical practitioners in Africa to determine their experiences of diagnosing and treating SLE patients, and the results suggest that significant numbers of African patients are presenting with SLE. The apparent low incidence rate in Africa may be the result of underdiagnosis due to poor access to health care, low disease recognition within primary health care settings, limited access to diagnostic tools and inadequate numbers of specialist physicians. Treatment of SLE in Africa is also restricted by availability and affordability of immunosuppressive drugs. We have established the African Lupus Genetics Network (ALUGEN), an informal network of clinicians and researchers in Africa who have an interest in SLE, in order to facilitate combined clinical and research efforts towards improved outcomes for African SLE patients.

Superheroes in autoimmune warfare: biologic therapies in current South African practice.

Biologic drugs targeting immune cells or cytokines underlying systemic inflammation have dramatically improved outcomes in patients with rheumatological and autoimmune diseases. Nine biologic drugs are currently available in South Africa (SA)--all showing good efficacy and safety profiles. Their high cost and potential adverse events preclude them from being used as first-line agents. They are therefore indicated for severe disease refractory to standard therapies, and their use must be initiated by a specialist. The most important adverse effect of this class of drugs is infection and, in SA, tuberculosis is of particular concern. As new targets in the immune system are identified, new biologics will be developed. The current challenges are to optimise standard care for all patients with autoimmune diseases, and to offer the appropriate biologic to patients with refractory disease.

Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis patients with nodules.

BACKGROUND: Immunohistochemical studies of the rheumatoid nodule (RN) suggest it is a Th1 granuloma, with focal vasculitis, yet the pathogenesis remains unclear and little is known about circulating cytokines in these patients. OBJECTIVE: We studied circulating cytokines in DMARD-naïve RA patients to investigate associations with subcutaneous RN. METHODS: 149 DMARD-naïve adults with early RA (symptom duration ≤ 2 years) were assessed using the Simplified Disease Activity Index (SDAI), and hand and feet radiographs were scored using the modified Larsen method. Circulating cytokines and growth factors representative of T-helper cell 1(Th1) and Th2 cell, macrophages, and fibroblasts were measured using the Bio-Plex® suspension array system. RESULTS: Of 149 patients, 34 (22.8%) had subcutaneous RN, and these patients had more severe disease with higher mean swollen joint counts (p=0.02), SDAI (p=0.04) and modified Larsen scores (p=0.004). There were no differences in Rheumatoid Factor or anti-cyclic citrullinated peptide antibody positivity between patients with RN and those without RN. Patients with RN showed significantly higher levels of circulating IL-12 (p=0.02), IL-2 (p=0.048), and VEGF (p=0.033) levels, with a trend towards higher levels of IL-7 (p=0.056), IFN-γ (p=0.059) and IL-8 (p=0.074) compared to those without RN. CONCLUSIONS: DMARD-naïve early RA patients with RN had more severe disease than those without RN, and showed an exaggerated circulating Th1 and macrophage cytokine profile.

Functional disability and health-related quality of life in South Africans with early rheumatoid arthritis.

BACKGROUND: The severity and predictors of functional disability and health-related quality of life (HRQoL) in a cohort of South Africans with early rheumatoid arthritis (RA) were investigated. METHODS: Changes in the Health Assessment Questionnaire Disability Index (HAQ) and the 36-Item Short Form Health Survey (SF-36) following 12 months of traditional disease-modifying anti-rheumatic drugs (DMARDs) were studied in previously DMARD-naïve adults with disease duration ≤ 2 years. RESULTS: The majority of the 171 patients were female (82%), Black Africans (89%) with a mean (SD) symptom duration of 11.6 (7.0) months. In the 134 patients seen at 12 months, there were significant improvements in the HAQ and all domains of the SF-36 but 92 (69%) still had substantial functional disability (HAQ > 0.5) and 89 (66%) had suboptimal mental health [SF-36 mental composite score (MCS) < 66.6]. Multivariate analysis showed that female sex (p = 0.05) and high baseline HAQ score (p < 0.01) predicted substantial functional disability at 12 months. Unemployment (p = 0.03), high baseline pain (p = 0.02), and HAQ score (p = 0.04) predicted suboptimal mental health, with a trend towards a low level of schooling being significant (p = 0.08). CONCLUSIONS: Early RA has a broad impact on HRQoL in indigent South Africans, with a large proportion of patients still showing substantial functional disability and suboptimal mental health despite 12 months of DMARD therapy. Further research is needed to establish the role of interventions including psychosocial support, rehabilitation programmes, and biological therapy to improve physical function and HRQoL in this population.

Response to traditional disease-modifying anti-rheumatic drugs in indigent South Africans with early rheumatoid arthritis.

The clinical response to traditional disease-modifying anti-rheumatic drugs (DMARDs) in indigent South Africans with early rheumatoid arthritis was investigated. A cohort of patients with early (≤2 years) RA who were DMARD-naïve at inception were prospectively assessed for response to DMARDs using the Simplified Disease Activity Index (SDAI) over a 12-month period. Patients with low disease activity (LDA) at 12 months were compared to those with moderate and high disease activity with respect to demographic, clinical, autoantibody and radiographic features. The 171 patients (140 females) had a mean (SD) age of 47.1 (12.4) years, symptom duration of 11.7 (7.1) months and baseline SDAI of 39.4 (16.2). There was a significant overall improvement in the SDAI and its components in the 134 (78.4%) patients who completed the 12 months visit, but only 28.4% of them achieved LDA. The majority of patients (91%) were treated with methotrexate as monotherapy or in combination with chloroquine and/or sulphasalazine. Baseline features that independently predicted a LDA state at 12 months were lower Health Assessment Questionnaire Disability Index (p = 0.023) and a higher haemoglobin level (p = 0.048). Receiver operating characteristic curve analysis showed that the 6-month SDAI was better than the baseline SDAI in predicting the 12-month SDAI (area under the curve of 0.69 vs. 0.52, respectively, p = 0.008). In conclusion, less than a third of the patients achieved a low disease activity at 12 months on traditional DMARDs. Patients who have an inadequate response to traditional DMARDs at 6 months are unlikely to show further improvement on traditional DMARDs at 12 months. These findings underscore the need for better disease control by an aggressive tight control strategy, including intense patient education and biologic therapy.

Remifentanil in paediatric anaesthetic practice.

Remifentanil is a synthetic opioid, first introduced into clinical practice in 1996. Its unique pharmacokinetic profile has resulted in a gradual increase in its popularity in paediatric anaesthesia. It is an opioid of high potency and rapid clearance, consequently lacking problems of accumulation. These characteristics give it a high degree of predictability and it has become an attractive choice for a wide variety of anaesthetic challenges, from premature neonates to the elderly. Neonates and infants have a higher clearance than older children and, as a result, remifentanil has additional benefits in this group. Remifentanil can be described as the only consistently predictable opioid in paediatric practice.

Osteoarticular tuberculosis in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) patients are at increased risk of developing tuberculosis (TB), particularly extrapulmonary TB (ExP-TB). AIM: The present study was undertaken to investigate whether SLE patients showed increased susceptibility to develop osteoarticular TB (OA-TB). DESIGN AND METHODS: We retrospectively reviewed and compared the frequency of ExP-TB, in particular OA-TB, in patients with SLE at a tertiary hospital in South Africa, to a non-SLE control TB group seen at the same hospital. RESULTS: TB was diagnosed 111 times in 97 (17%) of the 568 SLE patients. The relative frequency of ExP-TB in the SLE group (25.2%) was significantly lower than in the control group (38.5%) (OR = 1.9, P = 0.006). In contrast, OA-TB was diagnosed in the SLE group in nine (8.1%) patients (seven with peripheral arthritis and two with TB spine) compared to 54 (0.4%) in the overall control group (OR = 20.8, P < 0.001) and 13 (0.2%) in the subgroup of known HIV positive patients in the control group (OR = 44.4, P < 0.001). Within the SLE group, Black ethnicity (P = 0.003), lymphopaenia (P = 0.001), C3/C4 hypocomplementaemia (P = 0.05), corticosteroids [maximum dose (P = 0.002) and duration of treatment (P = 0.02)] and immunosuppressive agents (P = 0.02) were risk factors for TB. Duration of corticosteroid therapy was the only risk factor for OA-TB (P = 0.04). CONCLUSION: While the relative frequency of ExP-TB was lower in the SLE group compared to the control group, our findings suggest that SLE patients are at particular risk of developing OA-TB. Further prospective studies are needed to better understand the mechanisms that predispose SLE patients to OA-TB.