APLAR Grand Round Blackboard

Question 1

A 58-year-old man who was a smoker and a non-drinker presented with pain in both hands for the last six weeks. The pain was aggravated for the past week with joint swelling and early morning stiffness lasting more than an hour. On physical examination, his proximal interphalangeal joints, metacarpophalangeal joints, and wrists were swollen and tender. He did not have any other significant medical or surgical history apart from a positive family history of his maternal uncle, who had rheumatoid arthritis. His baseline laboratory findings were as follows: haemoglobin 10.2 g/dl, white blood cell count 4,500/µl, platelets 184,000/µl, alanine transaminase (ALT) 47 U/l, urea 5.1 mmol/l, creatinine 110 µmol/l, erythrocyte sedimentation rate 54 mm/hr, rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive. You decided to start him on methotrexate and low-dose steroids. How should the blood tests be monitored with methotrexate?

Your Answer is Incorrect

Answer with Detailed explanation

The correct answer is A. Complete blood count, ALT and creatinine every 2-4 weeks until three months of therapy, 8-12 weekly until six months of treatment and 12 weekly thereafter.

Methotrexate is the first-line drug for treating rheumatoid arthritis. But 20-30% of patients have to stop the medication due to various side effects, including gastrointestinal disturbance and hepatotoxicity, affecting 20-70% of cases (depending upon severity)1. Bone marrow suppression is less common (affecting 1-2%) but has potentially life-threatening complications. So, patients should be monitored regularly for these complications. American College of Rheumatology recommends laboratory monitoring of complete blood count, liver transaminases and creatinine 2-4 weekly for the first three months of starting treatment, then every 8-12 weeks until six months of therapy and three monthly thereafter2. Therefore, options B and C are incorrect. Option D is wrong, as hepatitis screening is recommended only at baseline when starting methotrexate. Option A is the correct answer.

Reference

1. Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502–516.
2. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784.

Dr Shahida Perveen, Registrar, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Saba Samreen, Assistant Professor, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Babur Salim, Associate Professor of Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan

Your Answer is Correct

Answer with Detailed explanation

Methotrexate is the first-line drug for treating rheumatoid arthritis. But 20-30% of patients have to stop the medication due to various side effects, including gastrointestinal disturbance and hepatotoxicity, affecting 20-70% of cases (depending upon severity)1. Bone marrow suppression is less common (affecting 1-2%) but has potentially life-threatening complications. So, patients should be monitored regularly for these complications. American College of Rheumatology recommends laboratory monitoring of complete blood count, liver transaminases and creatinine 2-4 weekly for the first three months of starting treatment, then every 8-12 weeks until six months of therapy and three monthly thereafter2. Therefore, options B and C are incorrect. Option D is wrong, as hepatitis screening is recommended only at baseline when starting methotrexate. Option A is the correct answer.

Reference

1. Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502–516.
2. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784.

Dr Shahida Perveen, Registrar, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Saba Samreen, Assistant Professor, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Babur Salim, Associate Professor of Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan

Question 2

A 52-year-old lady with rheumatoid arthritis presented with headache and decreased vision for 18 hours, followed by two episodes of generalised tonic-clonic seizures in the last 8 hours. She was drowsy. Her vital signs were as follows: blood pressure 168/100 mmHg, heart rate 72 bpm, respiratory rate 22 breaths/min, temperature 37°C and SaO2 94% on room air. Her plasma blood glucose was 191 mg/dl. There was no sign of meningeal irritation or focal neurological deficit. She was on prednisolone 5mg daily, methotrexate 20mg weekly, and naproxen 500mg as needed. She received a rituximab infusion three days ago for high disease activity. What would you expect from her imaging?

Your Answer is Incorrect

Answer with Detailed explanation

The correct answer is C. MRI showed bilaterally symmetrical hyperintensities in parieto-occipital white matter.

Posterior reversible encephalopathy syndrome (PRES)/ Reversible cerebral vasoconstriction syndrome (RCVS) is a multifactorial disorder with an estimated prevalence of 0.4-24%. It can be precipitated by various autoimmune diseases and immunosuppressive drugs. Several case reports of this disorder are described after rituximab. Brain imaging is needed to confirm the diagnosis. Imaging findings are usually bilateral and symmetrical, involving mainly parieto-occipital regions of the brain. CT scan usually shows hypodensities but may be normal initially. So, option A is incorrect. MRI is the most helpful imaging modality. It shows vasogenic edema, visible as hyperintense lesions on the FLAIR sequence. So, options B and D are incorrect. Option C is the correct answer.

Reference

1. Hinduja A. Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome. Front Neurol. 2020;11:71.

Dr Shahida Perveen, Registrar, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Saba Samreen, Assistant Professor, Fauji Foundation Hospital, Rawalpindi, Pakistan
Dr Babur Salim, Associate Professor of Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan

Your Answer is Correct

Answer with Detailed explanation

The findings in PRES are usually bilaterally symmetrical. The most commonly described abnormality in PRES consists of symmetrical cortical and subcortical hyperintense signals on T2 and FLAIR-weighted MR images in the parieto-occipital lobes of both hemispheres. Similar areas of altered signal intensity can also be seen in other locations such as the frontal lobes, cerebellum, brainstem and basal ganglia. Petechial and extensive parenchymal haemorrhages may be seen in up to 20% of the patients with PRES. This complication is more common in patients with coagulopathy or thrombocytopenia. Diffusion-weighted imaging (DWI) aids in the distinction of PRES from a top-of-the-basilar stroke. The vasogenic edema characteristic of PRES is usually visualised as a hypo- or isointense signal on DWI and increased signal on apparent diffusion coefficient (ADC) maps.

Reference

1. Raman, Rajesh et al. “Various Imaging Manifestations of Posterior Reversible Encephalopathy Syndrome (PRES) on Magnetic Resonance Imaging (MRI).” Polish journal of radiology vol. 82 64-70. 7 Feb. 2017, doi:10.12659/PJR.899960
2. Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol. 2002 Jun-Jul;23(6):1038-48. PMID: 12063238; PMCID: PMC7976914.
3. Lai CC, Chen WS, Chang YS, Wang SH, Huang CJ, Guo WY, Yang WC, Huang DF. Clinical features and outcomes of posterior reversible encephalopathy syndrome in patients with systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1766-74. doi: 10.1002/acr.22047. PMID: 23687067.

By Dr Shweta Nakarmi, Consultant Rheumatologist, National Center for Rheumatic Diseases, Kathmandu, Nepal