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 Table of Contents  
CASE SERIES
Year : 2022  |  Volume : 1  |  Issue : 2  |  Page : 121-126

Obesity as a trigger for autoimmune rheumatic diseases: Case series


Department of Medicine, Vydehi Institute of Medical Science and Research Centre, Bengaluru, Karnataka, India

Date of Submission31-Mar-2022
Date of Decision18-Apr-2022
Date of Acceptance19-Apr-2022
Date of Web Publication16-Jul-2022

Correspondence Address:
Meenakshi Kalyan
Department of Medicine, Vydehi Institute of Medical Science and Research Centre, Whitefield, Bengaluru - 560 066, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cdrp.cdrp_3_22

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  Abstract 


The chronic low-grade inflammation in obesity and multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of various rheumatic autoimmune and inflammatory conditions. Obesity is a low-grade systemic inflammatory condition with elevated levels of inflammatory markers such as leptin, C-reactive protein, tumor necrosis factor-α, and interleukin-6. Dysregulation of the cytokines and adipokines is a feature of metabolic syndrome, suggesting a complex relationship between autoimmunity, obesity, and atherosclerosis. We discuss the effects of obesity and its association with newly diagnosed immune-mediated disorders such as Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and antiphospholipid antibody syndrome in a case series of eight patients.

Keywords: Autoimmune rheumatic diseases, C-reactive protein, obesity


How to cite this article:
Hemanth Kumar H R, Kalyan M, Vedula A, Kolli C, Saba S, Dharma S. Obesity as a trigger for autoimmune rheumatic diseases: Case series. Chron Diabetes Res Pract 2022;1:121-6

How to cite this URL:
Hemanth Kumar H R, Kalyan M, Vedula A, Kolli C, Saba S, Dharma S. Obesity as a trigger for autoimmune rheumatic diseases: Case series. Chron Diabetes Res Pract [serial online] 2022 [cited 2022 Aug 10];1:121-6. Available from: https://cdrpj.org//text.asp?2022/1/2/121/351235




  Introduction Top


Obesity is a low-grade systemic inflammatory condition with elevated levels of inflammatory markers such as leptin, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6). The proinflammatory adipokine and leptin secreted excessively in obesity by adipocytes is a potent immune modulator possibly playing an important role in the development of autoimmune diseases. Dysregulation of the cytokines and adipokines is a feature in metabolic syndrome (MetS), suggesting a complex relationship between autoimmunity, obesity, and atherosclerosis.[1],[2] We summarize new insights of obesity and its association with immune-mediated disorders such as Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and antiphospholipid antibody syndrome.


  Case Reports Top


Case 1

A 54-year-old male presented with proximal muscle weakness in both the upper and lower limbs associated with pain for 4 months. There was no fever, rash, dyspnea, bladder bowel disturbances, or cranial nerve involvement. On examination, tenderness in all muscles was present. Neurological examination revealed normal higher mental functions and cranial nerves. Fundus showed bilateral nonproliferative diabetic retinopathy (NPDR). Motor system examination revealed normal bulk of the muscles, hypotonia present in bilateral upper limb and lower limb with truncal muscle weakness, power 3/5 in right upper limb and lower limb. All deep tendon reflexes were diminished and plantars were flexors. Sensory system examination revealed impaired joint position and vibration in both the lower limbs with intact fine touch and pinprick sensations. The rest of the systemic examinations were within normal limits. Investigations revealed Hb of 11.2 g/dl, white blood cell (WBC) of 12,000/cumm, and platelets of 230,000/cumm. Erythrocyte sedimentation rate (ESR) was 54, creatine phosphokinase – 9663 U/L, and cortisol – 3.8 ug/dl. Liver function test (LFT), renal function test (RFT), electrolytes, uric acid, urine routine microscopy, thyroid function test (TFT), electrocardiography (ECG), and echocardiography were normal. Antinuclear antibody (ANA) by ELISA was 3+. Myositis profile showed anti-Jo-1 strongly positive 3+ and anti-RO52 strongly positive 3+. Electromyography of the right biceps brachii and vastus medialis showed increased insertional activity, profuse fibrillation and positive sharp waves, small amplitude, and polyphasic motor units, suggestive of myopathy consistent with polymyositis. With the above findings, a diagnosis of autoimmune disease of SS with polymyositis was made. He was treated with pulse therapy of intravenous methylprednisolone 500 mg once a day for 5 days, basal-bolus insulin regimen followed by oral prednisolone 60 mg OD with the improvement of muscle weakness. On follow-up visit, power in both the upper and lower limbs was 4 ± 5.

Case 2

A 45-year-old female presented with polyarthralgia involving small and large joints for 9 months and cough with sputum and progressive breathlessness for 6 months. On examination, tenderness was present in bilateral interphalangeal joints, wrists, knees and ankles with restriction of abduction movement in the left shoulder. Respiratory system revealed crepitations in the left interscapular area. Fundus showed mild NPDR in the left eye. Investigations revealed Hb – 11.9 mg/dl, WBC – 15,100/cumm, platelets – 130,000, ESR – 37, ANA 3 + by ELISA, anti-ds DNA positive (2+), urine micro total protein – 3 mg/dl, spot urine protein–creatinine ratio – 41.8, and CRP – 24 ug/ml. Complement levels of C3 and C4 levels were low. TFT, LFT, RFT, and electrolytes were normal. Reverse transcription–polymerase chain reaction COVID was negative. Sputum culture showed Klebsiella pneumonia. High-resolution computed tomography thorax showed fibrosis with traction bronchiectasis, interlobular septal thickening, and subpleural honeycombing involving the anterior and lingual segments of the left upper lobe. Patchy areas of subpleural ground glass opacities in the right upper lobe and bilateral lower lobes suggesting Interstitial lung disease (ILD) likely usual interstitial pneumonia [Figure 1]. With the above findings, diagnosis of SLE with ILD was made. She was treated with broad-spectrum antibiotics for 10 days for pneumonia, T. HCQ (Tablet hydroxychloroquine) 200 mg BD, T. sulfasalazine 500 mg BD, and basal bolus insulin regimen. Following the resolution of pneumonia, she was discharged with oral prednisolone 50 mg OD with the resolution of symptoms of polyarthralgia.
Figure 1: HRCT thorax suggestive of fibrosis with traction bronchiectasis, interlobular septal thickening, and subpleural honeycombing involving the anterior and lingual segments of the left upper lobe. Patchy areas of subpleural ground glassing opacities in the right upper lobe and bilateral lower lobes suggesting interstitial lung disease. HRCT: High-resolution computed tomography

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Case 3

A 47-year-old female presented with polyarthralgia, alopecia, and multiple skin lesions on the face, scalp, and neck for 1 year. On examination , discoid lesions seen on the face, scalp and presence of malar rash [Figure 2], discoid lesions on scapular region [Figure 3] and presence of alopecia [Figure 4]. Tenderness was present in all joints. Systemic examination was normal. Investigations revealed pancytopenia, ESR-56, ANA 2+ by ELISA, ANA 15 screen showed anti-RO52 and SSA RO 60 antibodies were positive. LFT, RFT, and TFT were normal. Urine routine showed proteins of 500 mg/dl, urine protein–creatinine ratio of 7.04, and urine for micro total protein – 783 mg/dl. Complement levels of C3 and C4 were low. With a SLE Disease Activity Index score of 16, a diagnosis of discoid lupus was made. Skin biopsy and renal biopsy were deferred due to thrombocytopenia. She was treated with oral prednisolone 60 mg OD, HCQ 200 mg BD, sulfasalazine 500 mg BD, telmisartan 40 mg OD, basal insulin, and metformin 500 mg BD.
Figure 2: Discoid lesions seen on the face, scalp, and malar rash

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Figure 3: Discoid lesions in the scapular region

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Figure 4: Alopecia

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Case 4

A 50-year-old female presented with polyarthritis involving the small and large joints associated with morning stiffness for more than 2 h for 1 year. On examination, tenderness of interphalangeal joints, wrists, shoulders, knees, and ankles bilaterally with limited restriction of movements was present with swan-neck deformity and Z-shaped deformity seen in interphalangeal joints [Figure 5]. X-ray hands were normal. Systemic examination and fundus of both the eyes were normal. Investigations revealed Hb – 8.8 g/dl, WBC – 8300, platelets – 408,000/cumm, peripheral smear shows microcytic hypochromic anemia, ESR – 81, CRP – 5.26, thyroid-stimulating hormone – 5.04 mIU/L, RA factor – <20.0, uric acid – 4.7 mg/dl, ANA 2 + by ELISA, anti-cyclic citrullinated peptide (CCP) was positive. LFT, RFT, and urine routine microscopy were normal. With the above findings, a diagnosis of RA was made. She was treated with T. methotrexate 7.5 mg once a week, T. sulfasalazine 500 mg BD, T. etoricoxib 60 mg BD, and a short course of oral prednisolone with T. metformin 500 mg BD and basal insulin.

Case 5

A 42-year-old male presented with pain in the wrists and interphalangeal joints associated with swelling for 1 year. On examination, tenderness in both the wrists and interphalangeal joints and swelling in both the wrists were present. Fundus was normal. Investigations revealed Hb – 13.5 g/dl, WBC – 6500, platelets – 120,000/cumm, ANA 2+ by ELISA, Anti-CCP was positive, LFT, RFT were normal. Urine micro total protein was 17.9, and spot urine protein–creatinine ratio was 177. X-ray wrist AP/lat (Anteroposterior/ Lateral) view was normal. Diagnosis of RA was made. He was treated with T. methotrexate 7.5 mg OD, T. sulfasalazine 500 mg BD, and T. etoricoxib 60 mg BD. He was on metformin 1 g BD, T. sitagliptin 50 mg BD, and basal insulin.

Case 6

A 40-year-old married female presented with sudden onset of weakness in the right upper limb and lower limb for 2 days. There was no history of cranial nerve involvement or bladder and bowel disturbances. She had a bad obstetric history of three miscarriages in the past following the birth of her first child who was 13 years old. She had a past history of right hemiparesis of grade 4/5 with left upper motor neuron facial palsy 3 years ago which resolved completely within 6 months following physiotherapy. Neurological examination revealed normal higher mental functions and cranial nerves, power of 3/5 in the right upper and lower limb, Deep tendon reflexes were diminished in the right upper and lower limb, the right plantar reflex was extensor. Fundus showed NPDR in both the eyes. The rest of the systemic examinations were normal. Investigations revealed complete blood count (CBC), LFT, RFT, and electrolytes; chest X-rays were normal. ECG and echo showed moderate left ventricular hypertrophy (LVH). Urine micro total protein was 286 and urine protein–creatinine ratio was 0.9. S. homocysteine (serum homocysteine) levels were 30 μmol/L. Antiphospholipid antibody (APLA) profile showed IgM. Anticardiolipin antibody by Chemiluminescence was moderate positive : 45 MPLU/ml. Magnetic resonance imaging (MRI) brain showed acute infarct in the left capsuloganglionic region, predominantly in the posterior limb of the left internal capsule suggesting hemorrhagic transformation and chronic lacunar infarcts in the right lentiform and left caudate nucleus [Figure 6].
Figure 5: Swan-neck deformity and Z-shaped deformity seen in interphalangeal joints

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Figure 6: MRI brain showing acute infarct in the left capsuloganglionic region. MRI: Magnetic resonance imaging

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Case 7

A 34-year-old male presented with a blurring of vision for 7 days and headache for 2 days. There was a history of regular alcohol consumption for 5 years. Fundus of both the eyes showed papilledema [Figure 7]. Systemic examination was normal. Investigations revealed CBC, LFT, RFT, and TFT were normal. Urine protein was 11.3 mg/dl, C3 – 75.8 mg/dl, and C4 – 35.3 mg/dl. 24-h urinary protein was 384.2 mg/day, urine protein–creatinine ratio – 0.64, urine micro total proteins – 36.9 mg/dl; ECG showed LVH, and echocardiography showed severe concentric LVH and grade 1 diastolic dysfunction. Renal Doppler showed grade 1 renal parenchymal disease. S. cortisol levels-7.81 ug/dl, s homocysteine levels were >65 micromol/L, ANA by ELISA was 2+, APLA profile showed lupus anticoagulant (LA) (clot detection) dilute Russell viper venom test was 48.8 s (reference value: 33–41 s), anticardiolipin antibody IgM <2.0 GPLU/ml. Extended thrombophilia profile showed protein C (chromogenic) – 84.9%, protein S (immunoturbidimetry) – 101.2%, activated protein C resistance (clot resistance) – 0.94, antithrombin III (chromogenic) – 96.2% (ref: 70%–121%) were negative. MRI brain showed altered signal intensity involving corona radiata suggesting acute infarct in the right corona radiata, with a possibility of adult-onset leukodystrophy [Figure 8]. He was treated with mannitol for 5 days, telmisartan 40 mg OD, amlodipine 5 mg OD, metoprolol extended-release 12.5 mg OD, prazosin 5 mg OD, and Homochek OD.
Figure 7: Fundus of both the eyes showing papilledema

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Figure 8: MRI brain suggestive of acute infarct in the right corona radiate. MRI: Magnetic resonance imaging

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Case 8

A 29-year-old female presented with pain abdomen for 15 days. Abdomen examination revealed right renal angle tenderness. CBC, LFT, RFT and urine examination were normal. Contrast-enhanced computed tomography abdomen revealed persistent nonenhancing filling defect noted in the inferior vena cava at the level of D10 vertebra involving >50% of lumen extending for the length of 9.3 cm till superior endplate of L2 vertebra, filling defect extending into the right renal vein suggestive of thrombus. Two subtle wedge-shaped nonenhancing areas sparing the adjacent cortex in the mid and lower pole regions of the right kidney are suggestive of infarcts [Figure 9]. She was treated with low-molecular-weight heparin followed by oral anticoagulants. The clinical features and laboratory parameters of all eight patients are highlighted in [Table 1] and [Table 2].
Figure 9: CECT Abdomen suggestive of the right renal vein thrombus. CECT: Contrast-enhanced computed tomography

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Table 1: Clinical features of patients

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Table 2: Laboratory parameters of glycated hemoglobin, C-reactive protein, and lipids in patients

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  Discussion Top


MetS, which comprises hypertension, diabetes, and obesity, is closely related to autoimmune diseases such as RA, SLE, SS, and IL-17 is a proinflammatory cytokine involved in the pathogenesis.[3] The presence of a disease-specific adaptive immune response in the target organ can be indicative of autoimmune pathogenesis and increased prevalence of B cells, CD8 + T-cells, and T-helper (Th) 1 and Th17 T-cells has also been described in obesity-related insulin resistance. CRP is a sensitive marker of systemic inflammation synthesized by the liver, and repeated elevated levels suggest chronic inflammation with each degree of obesity related directly to CRP.[4] A cohort study conducted on Danish women showed a weak association between body mass index and RA, but obese women had a 1.5-fold increased risk of developing RA.[5] A study by Katz et al.[6] showed a high prevalence of obesity among individuals with RA, with men having higher rates of obesity and at high risk of cardiovascular disease and events, which is in similarity to the male obese Type 2 diabetes patient presenting with RA in case 5. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibodies in serum which acts against membrane phospholipids which include LA, anticardiolipin antibody, and anti-β2-glycoprotein I. APS can be primary or secondary to other autoimmune diseases. Tahlan et al.[7] reported multiple conventional risk factors in APS which include obesity, smoking, hypertension, diabetes, and dyslipidemia found similar to cases 6, 7, and 8. APS most commonly present with vascular ( Venous, arterial or small vessel) thrombosis, obstretic complications such as unexplained recurrent miscarriages, pre eclempsia, fetal growth restriction, angina and strokes.[8] Factors related to gender have been suggested to affect the clinical course in patients with primary APS, with a significant prevalence of a central nervous system involvement in females in comparison with gastrointestinal involvement in males.[9]


  Conclusion Top


Chronic low-grade inflammation can result in silent inflammation in autoimmune individuals that can remain undetected for years and may or may not precipitate into clinical presentation, depending upon complex interactions between immunological and environmental triggers. Understanding mechanisms and association need further investigation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mok CC. Metabolic syndrome and systemic lupus erythematosus: The connection. Expert Rev Clin Immunol 2019;15:765-75.  Back to cited text no. 1
    
2.
Tsai S, Clemente-Casares X, Revelo XS, Winer S, Winer DA. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases? Diabetes 2015;64:1886-97.  Back to cited text no. 2
    
3.
Hwang SH, Park JS, Yang S, Jung KA, Choi J, Kwok SK, et al. Metabolic abnormalities exacerbate Sjögren's syndrome by and is associated with increased the population of interleukin-17-producing cells in NOD/ShiLtJ mice. J Transl Med 2020;18:186.  Back to cited text no. 3
    
4.
Choi J, Joseph L, Pilote L. Obesity and C-reactive protein in various populations: A systematic review and meta-analysis. Obes Rev 2013;14:232-44.  Back to cited text no. 4
    
5.
Harpsøe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, et al. Body mass index and risk of autoimmune diseases: A study within the Danish National Birth Cohort. Int J Epidemiol 2014;43:843-55.  Back to cited text no. 5
    
6.
Katz PP, Yazdany J, Trupin L, Schmajuk G, Margaretten M, Barton J, et al. Sex differences in assessment of obesity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2013;65:62-70.  Back to cited text no. 6
    
7.
Tahlan K, Sikka1 M, Avasthi R, Kotru1 M, Gogoi P, Gupta R. Antiphospholipid antibodies in young adults with myocardial infarction. Asian J Cardiol Res 2020;3:35-42.  Back to cited text no. 7
    
8.
Duarte-García A, Pham MM, Crowson CS, Amin S, Moder KG, Pruthi RK, et al. The epidemiology of antiphospholipid syndrome: A population-based study. Arthritis Rheumatol 2019;71:1545-52.  Back to cited text no. 8
    
9.
Jara LJ, Medina G, Vera-Lastra O, Barile L. The impact of gender on clinical manifestations of primary antiphospholipid syndrome. Lupus 2005;14:607-12.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
    Tables

  [Table 1], [Table 2]



 

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