A 29-year-old woman with a 12-year history of systemic lupus erythematosus (SLE), initially diagnosed on the basis of mucocutaneous involvement and recurrent disease flares, presented with progressively worsening dysphagia and persistent nausea, resulting in multiple hospital admissions over the preceding years.
Upper gastrointestinal endoscopy demonstrated pangastroduodenitis along with a grade I hiatal hernia, while colonoscopy revealed terminal ileal aphthous ulcers and features of colitis. Despite escalation of immunosuppressive therapy, including MMF, Azathioprine and administration of two pulses of intravenous cyclophosphamide, her gastrointestinal manifestations remained refractory.
Over the subsequent months, she developed systemic sclerosis characterized by perioral tightening, decreased oral aperture, and Raynaud’s phenomenon. In parallel, she reported worsening exertional dyspnea. High-resolution computed tomography (HRCT) of the chest revealed fibrotic nonspecific interstitial pneumonia (NSIP) pattern with multiple cystic changes. Pulmonary function testing demonstrated a restrictive ventilatory defect (total lung capacity 9.67 L) and impaired gas exchange with reduced diffusion capacity (DLCO 71%).
The six-minute walk test showed significant exertional desaturation to 86%. Transthoracic echocardiography excluded pulmonary arterial hypertension, while urinalysis revealed only trace proteinuria.
ANA profile demonstrated strong positivity for anti-mRNP/sm antibodies, with borderline reactivity for anti-PCNA and anti-Ku antibodies. In light of the evolving clinical picture—scleroderma-like cutaneous changes, interstitial lung disease, gastrointestinal dysmotility, and characteristic autoantibody profile—a diagnosis of mixed connective tissue disease (MCTD) was established.
The patient was counseled regarding the initiation of rituximab therapy given her refractory course and progressive systemic involvement.
Mixed Connective Tissue Disease (MCTD) is a distinct autoimmune overlap syndrome, first described by Sharp et al., characterized by high-titer anti-U1 RNP antibodies and a constellation of clinical features drawn from systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myositis, rheumatoid arthritis (RA), and Sjögren’s syndrome. The disease often follows an evolving course, with one phenotype predominating at different stages of illness, making longitudinal follow-up essential.
The usual initial presentation of MCTD is Raynaud’s phenomenon with puffy fingers and myalgia. With progression, patients may develop sclerodactyly, calcinosis, telangiectasia, and skin rashes resembling SLE (malar erythema, photosensitivity) or dermatomyositis (heliotrope rash, Gottron’s papules). Arthralgia is common, occasionally progressing to erosive polyarthritis. Systemic involvement includes pulmonary fibrosis, pulmonary arterial hypertension, esophageal dysmotility, pericarditis, and membranous glomerulonephritis.
Diagnosis is established through the coexistence of overlapping clinical features along with serological confirmation of anti-U1 RNP antibodies. The Alarcón-Segovia and Kasukawa criteria are most frequently employed in clinical practice.
The prognosis of MCTD is variable. Overall survival is often more favorable compared to isolated systemic sclerosis or polymyositis; however, long-term morbidity arises predominantly from progressive ILD, PAH, and severe musculoskeletal involvement. Treatment is individualized according to organ involvement and disease severity. Regular cardiopulmonary surveillance is imperative, given their prognostic impact.
In our patient, the initial presentation was consistent with MCTD with predominant SLE-like manifestations, chiefly mucocutaneous involvement. Over time, the clinical phenotype evolved with the development of cutaneous thickening, Raynaud’s phenomenon, and esophageal dysmotility, reflecting a transition toward systemic sclerosis. This shift has important prognostic implications, particularly with regard to heightened risk of PAH and ILD.
This case underscores the dynamic nature of MCTD, wherein disease expression evolves over time, often altering prognosis and therapeutic priorities. It highlights the necessity of a multidisciplinary approach and emphasizes that management should be guided by serial clinical assessments rather than static classification alone, as this directly influences long-term outcomes.
Dr. Madhumitha R M, MBBS 1st year DNB Resident (General Medicine) Kauvery Hospital, Alwarpet Chennai
Dr. Sham S, DM (RHEUMATOLOGY), MRCP(UK), FRCP(EDIN), SCE (RCP UK), SENIOR CONSULTANT, DEPARTMENT OF RHEUMATOLOGY Kauvery Hospital, Alwarpet Chennai
