Discussion of the case
The patient presented with gradual onset polyarthritis involving both small and large joints. She was positive for RF (previous consultation) and ANA with normal LFT. Given the absence of associated features like skin rashes and dry mouth/eyes, the diagnosis of RA was considered and was started on MTX and HCQ. Initially her clinical presentation except for oral ulcers and positive ANA she was fulfilling the ACR/EULAR 2010 criteria for RA.1 Concerning SLICC criteria oral ulcer and polyarthritis were clinical with ANA positive.2 The diagnosis of SLE was incomplete and RA seems to be a reasonable diagnosis at the initial point. Â Though U1n RNP was positive the patient had only arthritis and it is a minor criterion and does not support the diagnosis.
Improvement in pain and swelling was initially noted with the introduction of methotrexate and Hydroxychloroquine. The steroid deflazacort was gradually tapered. The patient revisited the clinic on an emergency basis with sudden deterioration in muscle strength and elevated SGOT and SGPT. Elevated CPK, and muscle weakness suggest myositis or myopathy.
The sudden deterioration noted in the present case could be due to disease progression as steroid was withdrawn, drug-induced myositis or myopathy, or unusual overlap of infection with muscle weakness. In addition to RF, the patient was positive for snRNP and SSA in the very initial presentation. Her myositis profile repeated at her emergency visit was negative. Â The developing myositis, an additional clinical feature suggests the diagnosis to be mixed connective tissue disease (MCTD). Alternatively, one can consider sn RNP-associated myositis.
In a case series of patients who were diagnosed with myositis in association with antibodies against snRNP, 3 out of 5 patients had symmetric distal arthritis.3Â The early presentation in the current case was typically like RA; but no additional symptoms in her initial visit, except arthritis, were reported. The case can be considered as snRNP-associated myositis. The probability of MCTD also needs to be considered, but the patient does not fulfill any of the classification criteria (Table 1 & 2).4,5,6,7
Table 1: Classification criteria for MCTD
| Sharp (1987) |
Kasukawa et al (1987) |
AlarcĂ³n-Segovia et al
(1987) |
| A. Major criteria
1) Myositis, severe
2) Pulmonary involvement
a. Diffusion capacity <70% of
normal values
b. Pulmonary hypertension
c. Proliferative vascular lesions on lung biopsy
3) Raynaud's phenomenon or
esophageal hypomotility
4) Swollen hands or sclerodactyly
5) Anti ENA ≥1:10,000 and anti-U1snRNP positive and anti-Sm negative
B. Minor criteria
1) Alopecia
2) Leukopenia
3) Anemia
4) Pleuritis
5) Pericarditis
6) Arthritis
7) Trigeminal neuropathy
8) Malar rash
9) Thrombocytopenia
10) Mild myositis
11) History of swollen hands
At least 4 major criteria plus anti-U1 snRNP titer of at least 1:4000 (exclusion criterion: positivity for anti-Sm); or 2 major criteria from among 1, 2, and 3 plus 2 minor criteria plus anti-U1 snRNP titer of at least 1:1000 |
A. Common symptoms
1) Raynaud's phenomenon
2) Swollen fingers or hands
B. Anti-U1 snRNP antibody
positive
C. Mixed symptoms
       I.           SLE-like findings
1) Polyarthritis
2) Lymphadenopathy
3) Facial erythema
4) Pericarditis or pleuritis
5) Leukopenia (<4000/mm3)
or thrombocytopenia
(<100,000/mm3)
Â
     II.            SSc-like findings
1) Sclerodactyly
2) Pulmonary fibrosis, restrictive changes of the lung (VC<80%), or reduced diffusion capacity
(DLCO <70%)
3) Hypomotility or dilatation of the esophagus
Â
   III.            PM-like findings
1) Muscle weakness
2) Elevated serum levels of muscle enzymes (CPK)
3) Myogenic pattern on EMG
At least 1 of the 2 common symptoms plus positive for anti-U1 snRNP plus 1 or more of the mixed symptoms in at least 2 of the 3 diseases categories |
A. Serologic
1) Anti-U1 snRNP at a hemagglutination titer of ≥1:1600
B. Clinical
1) Edema in the hands
2) Synovitis
3) Myositis
4) Raynaud's phenomenon
5) Acrosclerosis
Serologic criterion plus
at least 3 clinical criteria, including either synovitis or myositis |
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Table 2: Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee
| Tanaka Y, Kuwana M, Fujii T, et al. (2019) |
| I. Common manifestations
1. Raynaud’s phenomenon
2. Puffy fingers and/or swollen hands
II. Immunological manifestation
Positivity for anti-U1 ribonucleoprotein antibody
III. Characteristic organ involvement
1. Pulmonary arterial hypertension
2. Aseptic meningitis
3. Trigeminal neuropathy
IV. Overlapping manifestations
A. Systemic lupus erythematosus-like manifestations
1. Polyarthritis
2. Lymphadenopathy
3. Malar rash
4. Pericarditis or pleuritis
5. Leukopenia (4,000/lL or less) or thrombocytopenia (100,000/lL or less)
B. Systemic sclerosis-like manifestations
1. Sclerodactyly
2. Interstitial lung disease
3. Esophageal dysmotility or dilatation
C. Polymyositis/Dermatomyositis-like manifestations
1. Muscle weakness
2. Elevated levels of myogenic enzymes
3. Myogenic abnormalities on electromyogram
At least one common manifestation, immunological manifestation, and at least one characteristic organ involvement; or when a patient meets all the following: at least one common manifestation, immunological manifestation, and at least one feature each in 2 or more from items A, B, and C in overlapping manifestations. |
The other possibility is drug-related adverse events. The LFT had become abnormal after the first three months of treatment. But the LFT profile suggests that there is no evidence of hepatitis. Moreover, the elevation in SGPT/SGOT rise and normal levels of gamma-glutamyl transferase and alkaline phosphatase indicates that the underlying pathology is not liver-related. In addition, the increase in CPK levels substantiates muscle involvement. The development of muscle weakness due to drug-induced myositis is another possibility. There is literature evidence reporting the occurrence of myopathy induced by HCQ.8,9Â However, the drug-induced myopathy is slowly progressive, and in the current case, it was acute precipitating. Based on these observations, the diagnosis was finally concluded as polymyositis.
Final diagnosis
Anti-RNP-associated inflammatory polymyositis
Follow-up
In addition to ongoing MTX and HCQ treatment, the patient was managed with a tapering dose of steroids. The muscle weakness improved in 4 weeks and CPK had become normal by the end of 6 weeks.
Learning points
- Rise in Enzymes ALT/AST does not always indicate liver toxicity., muscle diseases may also cause an elevation of these enzymes. Careful workup of all the enzymes helps to consider the diagnosis
- A constant monitoring of newer symptoms of the same disease is warranted
- The drug effect should also be considered.
References
- Kay J, Upchurch KS. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology. 2012;51(suppl_6):vi5-vi9.
- Petri M, Orbai AM, AlarcĂ³n GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64(8): 2677–2686.
- Coppo P, Clauvel JP, Bengoufa D, Oksenhendler E, Lacroix C, Lassoued K. Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies: a subset of myositis associated with a favorable outcome. Rheumatology (Oxford). 2002 Sep;41(9):1040–6.
- Sharp GC, Anderson PC. Current concepts in the classification of connective tissue disease. J Am AcadDeramtol 1980;2:269-74.
- Kasukawa R, Tojo T, Miyawaki S. Preliminary diagnostic criteria for classification of mixed connective tissue disease. Mixed connective tissue disease and antinuclear antibodies. Kasukawa R, Sharp GC, editors. Amsterdam: Elsevier; 1987. p. 41-7.
- AlarcĂ³n-Segovia D, Villareal M. Classification and diagnostic criteria for mixed connective tissue disease. Mixed connective tissue disease and antinuclear antibodies. Kasukawa R, Sharp GC, editors. Amsterdam: Elsevier; 1987. p. 33-40.
- Tanaka Y, Kuwana M, Fujii T, et al. 2019 Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases. Mod Rheumatol. 2021;31(1):29-33.
- Casado E, GratacĂ³s J, Tolosa C, MartĂnez JM, Ojanguren I, Ariza A, et al. Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients. Ann Rheum Dis. 2006 Mar;65(3):385–90.
- Richards AJ. Hydroxychloroquine myopathy. J Rheumatol. 1998 Aug;25(8):1642–3.
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