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 Table of Contents  
Year : 2021  |  Volume : 16  |  Issue : 2  |  Page : 133-138

Treatment adherence and disease status among children with rheumatological diseases during COVID-19 pandemic: A cross-sectional study from a tertiary care center

1 Institute of Rheumatology, Madras Medical College and RGGGH, Chennai, Tamil Nadu, India
2 Department of Social and Preventive Medicine, Madras Medical College and RGGGH, Chennai, Tamil Nadu, India

Date of Submission21-Sep-2020
Date of Acceptance29-Nov-2020
Date of Web Publication25-Jun-2021

Correspondence Address:
Dr. Sabarinath Mahadevan
Institute of Rheumatology, Madras Medical College and RGGGH, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_267_20

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Introduction: There is a reallocation of health-care services across the world in view of the COVID-19 pandemic. This has resulted in the disruption of routine care to children with chronic rheumatological diseases. We studied the treatment adherence and disease status of these children during the COVID-19 pandemic.
Methods: We did a cross-sectional observational study of children (<16 years) with rheumatological diseases. Parents of seventy consecutive children with rheumatological diseases were interviewed through the telephone to assess the treatment adherence and disease status from April 2020 to July 2020.
Results: In our study cohort, 44.3' (n = 31) had juvenile idiopathic arthritis (JIA), 52.9' (n = 37) had childhood lupus childhood-onset systemic lupus erythematosus (cSLE), 1.4' (n = 1) had juvenile scleroderma, and 1.4' (n = 1) had childhood vasculitis. About 38.6' (n = 27) had poor compliance due to reasons like difficulty in transportation (88.6') (n = 24), financial constraints (88.6') (n = 24), fear of acquiring COVID-19 by attending the study center (55.5') (n = 15), and fear of taking immunosuppressive drugs (18.5') (n = 5). Thirty percent (n = 21) respondents reported flare of symptoms. Common flare symptoms reported were joint pain (25.7') (n = 18), skin rashes (1.4') (n = 1), and oral ulcers (1.4') (n = 1). One patient with cSLE required admission for acute pancreatitis. Nearly 4.3' (n = 3) experienced influenza like illness. One patient with cSLE developed swab-positive mild COVID-19 illness. cSLE patients experienced significantly less flare symptoms compared to patients with other rheumatological illness (P = 0.03, odds ratio = 0.32, confidence interval = 0.1–0.9). Almost 98.6' (n = 68) of parents were not aware of electronic consultation portals.
Conclusion: Although COVID-19 causes less symptomatic disease in children, this study highlights the indirect effects of pandemic like financial constraints and parental misconceptions on children with rheumatological diseases. Furthermore, the awareness about electronic portals in consultation needs to be increased.

Keywords: Childhood lupus, compliance, juvenile arthritis

How to cite this article:
Mahadevan S, Navaneethan B, Nikhila G S, Sreenath S, Mahabaleshwar M, Vishnupriya S, Tamilselvam T N, Selvan N P. Treatment adherence and disease status among children with rheumatological diseases during COVID-19 pandemic: A cross-sectional study from a tertiary care center. Indian J Rheumatol 2021;16:133-8

How to cite this URL:
Mahadevan S, Navaneethan B, Nikhila G S, Sreenath S, Mahabaleshwar M, Vishnupriya S, Tamilselvam T N, Selvan N P. Treatment adherence and disease status among children with rheumatological diseases during COVID-19 pandemic: A cross-sectional study from a tertiary care center. Indian J Rheumatol [serial online] 2021 [cited 2021 Sep 23];16:133-8. Available from:

  Introduction Top

The COVID-19 pandemic has paralyzed the health system across the world. During the pandemic, most of the tertiary care hospitals have reoriented themselves to cater mainly for COVID-19 patients. This may result in interruptions in the treatment of patients with chronic illness.[1] Furthermore, government measures like total lockdown may result in difficulty in accessing designated institutes caring for such patients. These problems are compounded in developing countries where the health department works under resource-limited settings. The severity of COVID-19 is comparatively less in children compared to adults. However, these indirect effects of COVID-19 pandemic may have equally devastating effects in children with chronic illness.

Children with autoimmune disorders are usually on long-term immunosuppressive medications. The altered immune system in autoimmune conditions and immunosuppressive treatment are known to be associated with severe infections.[2] This may influence patient compliance with medications. However, interruptions in treatment of these children may result in a disease flare. Such disease flare is in turn associated with an increased risk of infections among rheumatology patients.[3] Few studies have been done to assess the effect of COVID-19 pandemic on compliance and disease activity in adults with rheumatological disorders.[4],[5],[6] The treatment compliance and disease status of Indian children with rheumatological disorders during COVID-19 pandemic are not known.

The objective of our study was to assess compliance and disease status of children with rheumatological illness during COVID-19 pandemic. We also analyzed the factors influencing compliance and disease severity of these children during the COVID-19 pandemic.

  Methods Top

The study was conducted at the Institute of Rheumatology, in a tertiary care medical college hospital in South India. Ethical committee clearance was obtained from the institution ethical committee. No funding was obtained for the study. The institute functions as an apex government hospital catering for rheumatology patients all over the state. Children with rheumatological diseases (onset before 16th birthday) were followed in a speciality clinic. The unit policy was to follow-up these patients once in a month. At each visit, they undergo a physical examination for appearance of new symptoms and signs. Furthermore, they were dispensed medications free of cost for 1 month. Laboratory monitoring for complete blood count, renal function test and liver function test was done once in 3 months during follow-up. Additionally, special tests like C-reactive protein, complements C3 and C4, anti-dsDNA, and creatine phosphokinase were done on a case basis, as required during examination. Although specialty services were not stopped, the study center was predominantly functioning as a COVID-19 care center from April 2020 to July 2020. In addition, the intrastate transport was temporarily suspended during this period of the pandemic.

The objective of our study was to assess treatment adherence and disease status of children with rheumatological illness during the COVID-19 pandemic. We did a cross-sectional observational study from August 1, 2020,–August 20, 2020. A telephonic interview was conducted among parents of children with rheumatological illness. A convenient sample size of 85 pediatric rheumatology patients was selected. We included consecutive patients enrolled in the pediatric rheumatology clinic. Children who were under regular follow-up prior to the pandemic were included in the study. Contact details of these patients were retrieved from the registry. Parents of these children were administered a standard questionnaire [Appendix 1] through telephonic interview. Informed oral consent was obtained from the parent at the beginning of the interview. The questionnaire was administered in vernacular language by a single resident doctor and their responses were recorded. We excluded children whose parents could not be contacted after three telephone calls on consecutive days. We also excluded children whose parents were admitted in the hospital during the time of phone calls. Baseline data of these children, including details of medications, were collected [Table 1]. Parents who were unable to communicate the treatment details like drug name were requested to send the photocopy of the medication summary through phone (whatsapp/email). Treatment adherence, symptoms of disease flare, presence of COVID-19, or influenza-like illness (ILI) from April 2020 to July 2020 were interviewed. Questions on compliance to medications were asked. Children who continued treatment during the pandemic (April 2020 to July 2020) as advised in the study center were considered as having good compliance. Children who had interruptions in treatment (either prednisolone or nonsteroidal anti-inflammatory drug [NSAID] or immunosuppressives) or discontinued treatment during the above period were considered as having poor compliance. Furthermore, the reasons for poor compliance were inquired. For patients with good compliance, drug shortages, if any experienced, were also enquired. Details regarding self-medication of NSAID or steroids for symptom relief were recorded. Children with disease duration ≤2 years were considered as an early disease and those with more than 2 years as late disease. Disease flare symptoms were recorded as minor and major symptoms. Oral ulcers, joint pain, and skin rash were considered as minor flare symptoms. Any symptoms requiring hospitalization or life threatening were included under major flare symptoms. In addition, symptoms of ILI such as fever, cough, rhinorrhea, and sore throat in children during the study period were inquired. History of such illness with COVID-19 polymerase chain reaction (PCR) swab positive or chest computed tomography (CT) positive was taken as definite COVID-19 illness. History of confirmed COVID-19 illness (PCR or CT chest positive) in family members was also inquired. We also tried to analyze whether compliance and disease flare symptoms were associated with baseline diagnosis, disease duration, distance of the patient living place from study center, baseline steroid, NSAID use, and various immunosuppressives.
Table 1: Baseline data of pediatric rheumatology patients

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Descriptive statistics was used to study the data. Mean values with standard deviations (SDs) (mean ± SD) or median with range were used for demonstration of the data. Categorical variables were presented as counts and percentages. Chi-square test and Fisher's exact test were used to analyze the significance. P < 0.05 was taken as significant. IBM SPSS statistics software version 20.0 (Armonk, NY: IBM Corp.) was used for the statistical analysis.

  Results Top

Eighty-five consecutive children enrolled in the pediatric rheumatology clinic were included in the study. Fifteen patients could not be contacted after three attempts of a phone call. Seventy respondents were interviewed in the study. The baseline data of the respondents are summarized in [Table 1]. The most common rheumatological condition in our cohort was childhood-onset systemic lupus erythematosus (cSLE) (52.9'), followed by juvenile idiopathic arthritis (JIA) (44.3'). The most common immunosuppressive medication used was methotrexate (47.1'). Two patients of JIA were on etanercept along with methotrexate.

Nearly 38.6' (n = 27) of patients had poor compliance to treatment during the pandemic. Common reasons cited by parents for poor compliance include difficulties in transport due to lockdown (88.8', n = 24), financial crisis (88.8', n = 24), fear of acquiring COVID-19 by coming to the study center (55.5', n = 15), and fear of continuing immunosuppression (18.5', n = 5). Overall, 50' (n = 35) and 24.3' (n = 17) among the total respondents expressed concern over coming to the study center or continuing immunosuppressive medications during pandemic, respectively. About 45.7' (n = 32) of parents resorted to increase steroids or NSAID dose of their children for symptom relief without consultation. None of the patients who were compliant reported any shortage of drugs, particularly hydroxychloroquine (HCQ). About 32.1' (n = 9) of patients with early disease and 42.9' (n = 18) of patients with late disease had poor compliance, respectively. Nearly 51.5' (n = 17) of children residing more than 100 km from the study center and 33.3' (n = 5) of patients living within 20 km had poor compliance.

Overall, 30' (n = 21) of respondents reported flare in symptoms during the pandemic. The most common flare symptom reported was joint pain (25.7', n = 18), followed by skin rashes (1.4', n = 1) and oral ulcers (1.4', n = 1). The distribution of flare symptoms with respect to the diagnosis of JIA, systemic lupus erythematosus , and compliance is shown in [Table 2]. One patient with childhood lupus (cSLE) compliant with low-dose prednisolone and mycophenolate mofetil was admitted for acute pancreatitis. About 65.7' (n = 46) did not underwent routine laboratory monitoring as per the protocol in the study center. Nearly 42.4' (n = 14) of patients living >100 km from the study center developed flare symptoms compared to 26.7' (n = 4) of those residing within 20 km from the study center. Nearly 38.1' (n = 16) of patients with late disease had flare symptoms compared to 17.9' (n = 5) of patients with early disease.
Table 2: Distribution of flare symptoms with respect to diagnosis and compliance

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One patient with cSLE developed swab-positive mild COVID-19 illness (ILI present, swab positive, and chest CT normal). About 4.3' (n = 3) experienced ILI during the study period. They did not undergo nasal swab or chest CT. Nearly 4.3' (n = 3) respondents had at least one family member who was affected by COVID-19 (swab positive or CT chest suggestive). Almost 98.6' (n = 68) were not aware of the various electronic consultation portal introduced recently in the state.

No statistically significant difference in compliance was noted with respect to the diagnosis of JIA (P = 0.31) or cSLE (P = 0.26). There was no statistically significant difference in compliance irrespective of whether a patient was on steroids (P = 0.34) or NSAIDS (P = 0.31). Patients on intravenous cyclophosphamide (CYC) had good compliance compared to the patient on other oral immunosuppressive drugs. cSLE patients experienced significantly less flare symptoms compared to patients with other rheumatological illness (P = 0.03, odds ratio = 0.32, and confidence interval = 0.1–0.9). There was no statistically significant difference in flare between patients who continued treatment compared to those who had poor compliance (P = 0.12). There was no statistically significant association between distance from the study center with compliance (P = 0.08) or flare (P = 0.07). There were no statistically significant differences in early or late disease with respect to compliance (P = 0.03) or flare (P = 0.07).

  Discussion Top

About one-third (38.6') of our patients patient had to stop or interrupt treatment. The indirect effects of COVID-19 like complete lockdown and financial constraints had a significant impact on compliance, as observed in our study. In a study by Fragoulis et al. in adult rheumatology patients, therapy withdrawal was associated significantly with unemployment.[7] In a developing country like ours, the influence of these factors may continue well beyond the pandemic. The impact of lockdown and transport restrictions was understandably high in patients living more distance from the study center. More than half of our patients living beyond 100 km from the study center had poor compliance, although it was not statistically significant which may be due to the sample size limitations. In a study by Koker O et al., 49.2' of the patients declared that social restrictions, fear, and anxiety or new arrangements in health centers kept them away from access to health care.[8] Similarly, half of our study participants expressed concern to attend the study center due to fear of acquiring COVID-19. Such prejudices in addition to resulting in poor compliance may delay patients from seeking professional care in case of any complications. Furthermore, this may result in patients self-medicate with NSAIDS or steroids for symptomatic relief, as observed in half of our respondents in our study. Immunosuppressive medications form the core of rheumatology treatment. The concern of severe COVID-19 illness while taking these medications during pandemic also results in treatment interruption in a quarter of our patients. In general, discontinuation of treatment may lead to flares, and flares were in turn associated with increased risk of infections among rheumatological patients.[3] Hence, most advisory bodies recommend continuing immunosuppression treatment during the pandemic.[9],[10] CYC requires admission in hospital for intravenous administration. Contrary to our expectations, all three patients on CYC continued treatment. This may be because usually patients with severe disease are on CYC and they are less likely to interrupt treatment than those with milder illness. In our study, there is no statistically significant difference in compliance between children on NSAID, steroids, and children not on them. This was reassuring due to the fact that NSAID and steroids were thought to be associated with severe COVID-19 during the initial days of pandemic.[11] HCQ was used as a prophylactic and treatment option for COVID-19 during the early pandemic. This diversion was expected to result in a shortage of this drug for rheumatology patients as experienced in few centers.[12] In addition, securing and stockpiling of this drug by hospitals and government did happen during the early pandemic.[13],[14] However, none of our patients who were compliant experienced a shortage, possibly because of increased production of these drugs in the country itself.

Contrary to our concerns, almost two-third of our patients did not report any disease flare symptoms during our study period. Furthermore, among those with a flare of symptoms, the major flare was present in only one patient (cSLE with acute pancreatitis). Overall, cSLE patients experienced less flare symptoms compared to other children with rheumatological illness in our study. This may be because of avoidance of sunlight due to predominant indoor restrictions during lockdown. In addition, cSLE patients, owing to the severity and general disease nature, are likely to have good adherence to treatment compared to JIA patients. In our study also, cSLE patients have good compliance compared to JIA patients, although the difference was not statistically significant. Overall poor drug compliance was not significantly associated with flare symptoms in our cohort. This may be because of less number of patients experiencing flare symptoms in our cohort or symptomatic relief due to self-medication by patients. A longer duration of follow-up of those patients with poor compliance may also increase the number the children developing flare symptoms. Only one patient developed COVID-19 illness, contrary to the general expectation of increased possibility of COVID-19 infection in immunosuppressed patients. A similar risk of COVID-19 infections was observed among rheumatology patients compared to the general population in many centers.[15],[16],[17] Virtual consultations were already in use in several developed countries. Such services were being introduced in most centers in our country after the pandemic. However, awareness about such consultation services was highly lacking. Awareness of electronic consultation portals among patients needs to be increased in our setup. With COVID-19 pandemic duration uncertain, doctors and patients alike may need to maximize the use of electronic consultation portals.

The study was done 4 months after the start of pandemic. This may result in memory bias in recalling minor flare symptoms. However, it would be unusual for parents to forget major life threatening flares or those requiring admission. Furthermore, compliance was less likely to be influenced by memory bias. The flare symptoms interviewed were those that were perceived by parents. They may not be an absolute equivalent of disease activity or those that could be elicited in a hospital setting by a clinician. Nonetheless, this limitation may not have interfered in identifying major flares. Furthermore, we did not attempt to stratify parents with different educational backgrounds in their responses to the interviewer. We tried to negate this difference by using a single interviewer to administer the interview in vernacular language. Although it is reassuring that major flare symptoms either rheumatological or severe COVID-19 were not common in children, ours was a single center study. We may need long-term follow-up and multicenter collaboration of pediatric rheumatology centers to monitor for them. Furthermore, this will include more children with varied diagnoses to be studied, as most of our cohort were JIA and cSLE patients.

  Conclusion Top

The study highlights the treatment adherence and disease status of children with rheumatological illness during the COVID-19 pandemic. As such, the same issues may be pertinent to any childhood chronic illness. Although COVID-19 causes less symptomatic acute illness in children compared to adults, the results of this study will help in understanding how the indirect effects of COVID-19 such as financial constraints, transport difficulties, and patient perceptions influence health care. The results of this study may help the policymakers to plan for better follow-up and offer special care to children with a chronic illness during a pandemic situation like COVID-19. Hopefully, we learn early from the pandemic and offer specialized care to the patients in need, in addition to COVID-19 care.


The authors would like to thank the parents for participating in the interview.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Iannone F, Cantini F, Lapadula G. Diagnosis of latent tuberculosis and prevention of reactivation in rheumatic patients receiving biologic therapy: International recommendations. J Rheumatol Suppl 2014;91:41-6.  Back to cited text no. 2
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Schmeiser T, Broll M, Dormann A, Frabel C, Hermann W, Hudowenz O, et al. A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic. Z Rheumatol 2020;79:379-84.  Back to cited text no. 4
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  [Table 1], [Table 2]


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