Case study

Overlap syndrome of ankylosing spondylitis and mixed connective tissue disease in female

Nallasivan S^1*, Rajendran R², Mariappan S³, Palaninathan P⁴, Yadav K⁵, Sundara S⁶

 

Author Affiliations

^1-6Velammal Speciality Hospital and Research Institute, Anuppanadi, Madurai, Tamilnadu, India    

 

Correspondence: Dr. Subramanian Nallasivan

drsubramanian14@gmail.com

 

IJRCI. 2021;9(1):CS2

 

Submitted: 2 September 2021; Accepted: 21 October 2021; Published: 17 November 2021

 © IJRCI

Abstract

Introduction

Ankylosing spondylitis is a chronic inflammatory disease affecting the young men and less commonly women with a spectrum of manifestations including uveitis, arthritis, sacroiliitis, colitis and psoriasis (spondyloarthropathy, SpA). HLA B27 carrier has been found to be the genetic abnormality in many patients with SpA. Patients generally present with inflammatory back pain and peripheral arthritis that forms part of seronegative arthritis. Mixed connective tissue disease (MCTD) is the prototype of an overlap syndrome, since its original description by Sharp and colleagues in 1972, with clinical elements of scleroderma, lupus, polymyositis and anti-U1RNP antibodies.¹ It is characterized by circulating autoimmune antibodies that deposit in tissues, resulting in inflammatory response, and irreparable tissue damage. As per literature evidence, overlap and co-existence of these diseases are uncommon. The present study has reported the case of a 35-year-old female who had SpA for 10 years, and neck swelling for 4 months. She was found to have characteristic features of MCTD.

 

Case report

A 35-years-old female presented with multiple swelling in neck for 4 months and she was on sulfasalazine treatment for SpA (10 years). The empirical treatment for lymphatic TB for 3 months did not yield much benefit. Her clinical examination showed pallor, lymphadenopathy, and stomatitis with restricted spinal movements due to rigid spine. There was no history of fever or rash, but she had myalgia and fatigue. She did not have contact history with patient who was on anti-TB therapy.

 

Investigations showed microcytic hypochromic anemia (Hb: 6.2 gm/dl and MCV 68 mmol) with normal platelet (426000 /ul) and creatine kinase, and elevated ESR (61 mm) and LDH (1082 U/L). Direct Coombs test was positive. Peripheral smear showed microcytic hypochromic RBCs with moderate anisopoikilocytosis, target cells and elliptocytes. WBC was normal with few reactive lymphocytes and platelet levels were adequate. Mantoux was negative. Her spine MRI showed evidence of established ankylosed bamboo spine. Since the anesthetist expressed difficulty in intubation due to cervical spine deformities, bronchoscopy and excision biopsy of lymph node were not done. Fine needle aspiration cytology (FNAC) of submandibular lymph node showed features of reactive lymphoid hyperplasia (Fig 1). Her HLA B27 antigen was positive.

 

Fig. 1: FNAC lymph node with reactive lymhpoid cells

 

Ultrasound imaging of abdomen was normal. ECHO showed no evidence of pulmonary hypertension or pericardial effusion. HRCT of chest showed multifocal patchy areas of consolidation in bilateral lung fields. There were focal sub pleural ground glass appearances with surrounding tree-in-bud pattern in left upper lobe. (Fig. 2). There was no evidence of pleural effusion or hepatosplenomegaly.

 

Fig. 2: CT of chest with tree-in-bud appearance

 

Immunology investigations revealed: positive ANA (1 in 2560) and U1RNP antibodies, and negative anti-Smith antibodies, DsDNA, SARS CoV-2 IgG (0.09 COI), IgM (0.42 COI), and COVID RT-PCR and normal C3 and C4. Based on the clinical and lab investigations, it was inferred that she had long-standing ankylosed spine with features of connective tissue disease (CTD), Coombs positive hemolytic anemia and anti-U1-RNP positivity. The diagnosis was concluded as MCTD.

 

Specific features considered in the present case were polyarthritis, oral ulcers, weight loss, lymphadenopathy, Raynaud’s disease, anti-U1-RNP, and hemolysis. The differential diagnoses considered were tuberculosis, COVID infection, SLE, and lymphoma. The patient was treated with antibiotics for lung consolidation and subsequently with steroids.

 

Follow-up conducted after 6 weeks showed near total resolution of lung consolidation (Fig. 3), and normal weight gain and inflammatory markers. She was subsequently prescribed with azathioprine, prednisolone and calcium.

 

Fig 3. CT chest showing resolution of changes after treatment

 

Discussion

SpA and CTD are clinically distinct entities. However, a link between the two has been suggested by certain case studies either due to altered immunological behavior or due to drugs like sulfasalazine and biologics like TNF inhibitors. Sulfasalazine has been reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus. Lee et al. in (1999) and Pham et al. in (1999) have described earlier case reports of CTD in patients with ankylosing spondylitis.^{2, 3} Brandt and colleagues have reported (2002), the development of Sjogren’s syndrome along with MCTD in a patient with ankylosing spondylitis, while Dharmapaliah et al. (2018) have reported pulmonary hypertension in a patient with ankylosing spondylitis and CTD.^4,5 All the aforementioned case reports were described in male patients and had HLA-B27. Yongpeng and colleagues have reported manifestations of idiopathic inflammatory myopathy and ankylosing spondylitis.⁶ Chandrasekara et al. have described overlap syndrome of ankylosing spondylitis with SLE and dermatomyositis.⁷

 

The current case was reported in a female and she had HLA-B27 positivity with ankylosed spine. Earlier treatment with sulfasalazine had managed the disease reasonably well. Fever, weight loss and fatigue prompted further evaluation. Microcytic anemia, positive Coombs test, and negative COVID RTPCR and Mantoux test assisted in concluding the disease as CTD.

 

She did not manifest typical features described by Tanaka et al. such as hand edema, myositis, and mechanic hands; however, she had synovitis, fever, oral ulcers, Raynaud’s disease, and lymphadenopathy and lung infiltration with immunology showing anti-U1RNP antibodies, suggestive of MCTD.⁸

 

Competing interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

 

References

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2.     Lee JK, Jung SS, Kim TH, Jun JB, Yoo DH, Kim SY. Coexistence of ankylosing spondylitis and mixed connective tissue disease in a single patient. Clin Exp Rheumatol. 1999 Mar-Apr;17(2):263.

3.     Pham T, Daumen-Legre V, Lafforgue P. Concomitant spondylarthropathy and CREST syndrome. Clin Exp Rheumatol. 1999 Nov-Dec;17(6):754.

4.     Brandt J, Maier T, Rudwaleit M, Kühl U, Hiepe F, Sieper J, Braun J. Co-occurrence of spondyloarthropathy and connective tissue disease: development of Sjögren’s syndrome and mixed connective tissue disease (MCTD) in a patient with ankylosing spondylitis. Clin Exp Rheumatol. 2002 Jan-Feb;20(1):80-4.

5.     Dharmapalaiah C, Ms B, Sn P. Spine and a weak heart: a case of long standing ankylosing spondylitis developing pulmonary arterial hypertension secondary to mixed connective tissue disease, conferring poor prognosis. Annals of the Rheumatic Diseases 2020;79:1928-1929.

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7.     Chadrasekhara P, Jayachandran N, Rajasekharan L, Narsimulu G. P71 SLE, dermatomyositis and ankylosing spondylitis overlap-a case report. Indian Journal of Rheumatology. 2006; 3 (1):171-172.

8.     Tanaka Y, Kuwana M, Fujii T, Kameda H, Muro Y, Fujio K, 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. Modern Rheumatology. 2021 Jan;31(1):29-33.