Interstitial lung disease (ILD) stands as a significant pulmonary complication in individuals with connective tissue diseases (CTDs), contributing substantially to both morbidity and mortality. While CTDs associated with ILD are often grouped due to their shared autoimmune characteristics, the reality is a spectrum of distinct clinical presentations and management strategies for ILD within each specific CTD. This inherent heterogeneity, coupled with the multidisciplinary nature of patient care, has presented challenges in conducting large-scale, prospective treatment trials and has complicated our understanding of ILD development in CTD patients. This article aims to provide an updated perspective on the diagnosis of CTD-ILD, focusing on systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We will explore risk factors, diagnostic criteria, and key elements of clinical evaluation that heighten suspicion for Ctd-ild Diagnosis, as well as insights into the subgroup of patients with ILD exhibiting autoimmune features without fully meeting CTD diagnostic criteria. A meticulous and systematic approach to ctd-ild diagnosis is paramount, potentially uncovering unrecognized CTDs or autoimmune underpinnings in patients initially diagnosed with idiopathic ILD.
Connective tissue diseases encompass a broad range of pulmonary complications, including bronchiolitis, bronchiectasis, pleuritis, and pulmonary hypertension. Among these, interstitial lung disease (ILD) emerges as a prevalent and severe manifestation, characterized by diverse patterns of inflammation and fibrosis detectable through high-resolution CT (HRCT) scans and lung biopsy analysis. Advancements in classifying radiologic and pathologic patterns in idiopathic interstitial pneumonias are now being applied to CTD patients, although alternative classification systems based on cellularity and fibrosis levels have been proposed. 1,2 The British Thoracic Society guidelines offer a framework for addressing both idiopathic and secondary ILD, including CTD-ILD, emphasizing a multidisciplinary approach involving rheumatologists as the “gold standard” for diagnosis and management. 3
While CTD and ILD diagnoses frequently occur concurrently or sequentially, some individuals present with ILD years before a CTD diagnosis. Furthermore, a subset of patients exhibits predominantly or exclusively pulmonary manifestations of autoimmune disease. Therefore, pulmonologists must maintain a high index of suspicion and diligently evaluate for underlying CTD in all ILD patients. Our recommended clinical approach for ctd-ild diagnosis is outlined in Table 1.
Clinical Evaluation for CTD-ILD Diagnosis
A comprehensive clinical evaluation is the cornerstone of ctd-ild diagnosis. This process involves a detailed patient history, thorough physical examination, and targeted laboratory investigations to identify potential underlying connective tissue diseases.
Table 1. Clinical Approach to Evaluating Patients With ILD for CTDs
| Clinical Evaluation | Approach |
|---|---|
| Key elements of history | Presence of: |
| Rashes | |
| Raynaud phenomenon | |
| Constitutional symptoms | |
| Arthralgias | |
| Sicca symptoms | |
| Dysphagia | |
| Proximal muscle weakness | |
| Physical examination | Evaluate for: |
| Rashes | |
| Mechanic’s hands | |
| Gottron papules | |
| Sclerodactyly | |
| Digital ulcers | |
| Synovitis | |
| Oral ulcers | |
| Proximal muscle weakness | |
| Laboratory | Antinuclear antibody |
| Anti-double-stranded DNA | |
| Anti-ribonucleoprotein antibody | |
| Anti-Smith antibody | |
| Anti-Scl-70 | |
| Anti-Ro (SSA) | |
| Anti-La (SSB) | |
| Rheumatoid factor | |
| Anticyclic citrullinated peptide | |
| Anti-Jo-1 antibody | |
| Creatine kinase | |
| Aldolase | |
| Erythrocyte sedimentation rate | |
| C-reactive protein | |
| Pulmonary function testing, 6-min walk test | Perform at diagnosis and for serial monitoring: |
| Total lung capacity | |
| FVC | |
| DLCO | |
| 6-min walk distance and oxygen saturation | |
| Radiographic | All patients should undergo HRCT scan |
| NSIP pattern seen most often in CTD-ILD | |
| Pathologic | Utility of surgical lung biopsy specimen in established CTD-ILD unclear |
| Biopsy samples from upper, middle, and lower lung fields | |
| OP and cellular NSIP more likely to respond to immunosuppressive treatment |
Anti-Jo-1 = antihistidyl transfer RNA synthetase; anti-Scl-70 = autoantibodies targeted against type I topoisomerase; CTD = connective tissue disease; DLCO = diffusing capacity of lung for carbon monoxide; HRCT = high-resolution CT; ILD = interstitial lung disease, NSIP = nonspecific interstitial pneumonia; OP = organizing pneumonia; SSA = Sjögren syndrome antigen A; SSB = Sjögren syndrome antigen B.
Key Elements of History and Physical Examination in CTD-ILD Diagnosis
The patient’s medical history should be meticulously reviewed for symptoms suggestive of CTD, including rashes, Raynaud phenomenon, constitutional symptoms (fatigue, fever, weight loss), arthralgias, sicca symptoms (dry eyes, dry mouth), dysphagia, and proximal muscle weakness. Physical examination should focus on identifying signs associated with CTDs, such as various types of rashes, mechanic’s hands, Gottron papules, sclerodactyly, digital ulcers, synovitis, oral ulcers, and proximal muscle weakness. Recognizing these subtle yet crucial clinical clues is vital for prompting further investigation into ctd-ild diagnosis.
Laboratory Investigations for CTD-ILD Diagnosis
Laboratory testing plays a pivotal role in supporting ctd-ild diagnosis. A standard autoimmune panel typically includes antinuclear antibody (ANA), rheumatoid factor (RF), and antibodies specific to various CTDs, such as anti-double-stranded DNA, anti-ribonucleoprotein antibody, anti-Smith antibody, anti-Scl-70, anti-Ro (SSA), anti-La (SSB), anticyclic citrullinated peptide (anti-CCP), and anti-Jo-1 antibody. Furthermore, muscle enzymes like creatine kinase and aldolase, along with inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein, can provide additional supportive evidence. Pulmonary function testing and 6-minute walk tests are essential for assessing the severity of ILD and for longitudinal monitoring. Radiographically, HRCT is indispensable, with the nonspecific interstitial pneumonia (NSIP) pattern being the most frequently observed in CTD-ILD. While surgical lung biopsy may be considered in certain cases, its utility in established CTD-ILD is less clear.
CTD-Specific Considerations in ILD Diagnosis
Systemic Sclerosis (SSc) – ILD Diagnosis
Systemic sclerosis (SSc) is a heterogeneous connective tissue disease marked by excessive collagen deposition. 4 Updated diagnostic criteria for SSc are under development by rheumatology societies. 5,6 SSc is categorized into limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subtypes based on the extent of skin thickening. Traditionally, pulmonary hypertension was considered more prevalent in lcSSc, while ILD was linked more strongly to dcSSc. 7,8 However, research suggests that ILD risk is significant across both subtypes, emphasizing the importance of vigilant ctd-ild diagnosis in all SSc patients. 7
Gastroesophageal reflux, frequently observed in SSc due to esophageal involvement, is recognized as a risk factor for both the development and progression of SSc-ILD. 9 Esophageal dilation, a common radiographic finding in SSc, can be present even without overt esophageal symptoms. 10 Studies have shown a correlation between gastroesophageal reflux, particularly proximal reflux episodes, and the severity of pulmonary fibrosis in SSc-ILD, suggesting a potential mechanistic link. 11 While preliminary studies suggest potential benefits of antireflux medications in SSc-ILD, further validation is needed. 12
Median survival for SSc-ILD is estimated at 5 to 8 years. 13 HRCT findings in SSc-ILD typically include ground glass opacities and fibrosis. 14 Disease extent on HRCT and forced vital capacity (FVC) are used for staging and prognostication. 15 Retrospective analyses suggest that patients with more extensive reticular opacities on HRCT might derive greater benefit from cyclophosphamide therapy. 16 The Scleroderma Lung Study, a landmark randomized controlled trial, investigated cyclophosphamide in SSc-ILD, demonstrating a modest slowing of pulmonary function decline. 17,18 While cyclophosphamide’s role remains debated, mycophenolate mofetil has emerged as a promising alternative, with ongoing trials comparing its efficacy to cyclophosphamide in SSc-ILD. 21‐24 Hematopoietic stem cell transplantation has also shown potential in severe SSc-ILD, but requires further investigation. 25 Rituximab has been reported effective in refractory cases. 26‐28 Various immunosuppressive therapies are utilized in SSc-ILD, as summarized in Table 2.
Rheumatoid Arthritis (RA) – ILD Diagnosis
Rheumatoid arthritis (RA), a chronic inflammatory disease primarily affecting joints, is also associated with ILD, impacting survival and often correlating with more severe joint disease and tobacco use. 38‐41 Updated RA diagnostic criteria aim for earlier disease detection. 38 ILD diagnosis can precede RA diagnosis in some cases. 40 Multiple radiographic and histopathologic patterns exist in RA-ILD, influencing prognosis. Usual interstitial pneumonia (UIP) pattern on HRCT is associated with poorer survival compared to NSIP. 42 While NSIP may respond to immunosuppression, evidence for UIP treatment is limited. 43 Interestingly, RA-ILD patients with UIP may have better survival than those with idiopathic pulmonary fibrosis (IPF). 44
Initial treatment for newly diagnosed RA-ILD often involves high-dose prednisone. 45 Evidence for subsequent immunosuppressive agents is less robust, primarily from case reports and series. Older reports mention azathioprine or cyclosporine. 45 Newer agents like mycophenolate mofetil, TNF-α inhibitors (infliximab), and IL-6 receptor inhibitors (tocilizumab) have shown promise in case reports, but lack strong evidence for routine use. 29,34,46 Rituximab is under investigation for RA-ILD. 47
Drug-induced pneumonitis is a critical differential diagnosis in suspected RA-ILD. Medication review is essential. Diagnosis requires excluding infection, radiographic evidence of interstitial or alveolar opacities, and consistent histopathology if available. Methotrexate should be avoided in RA patients with established ILD. 48 Baseline chest radiographs and pulmonary function tests may be considered before methotrexate initiation. 49 Leflunomide and rituximab can also induce pneumonitis. 50,51 Treatment involves drug discontinuation and corticosteroids. In summary, diverse patterns are seen in RA-ILD, and drug-induced pneumonitis must be considered. Prednisone is first-line therapy, with limited evidence guiding further immunosuppression.
Dermatomyositis and Polymyositis (DM/PM) – ILD Diagnosis
Dermatomyositis and polymyositis are characterized by muscle inflammation, often affecting skin and lungs. Skin findings in dermatomyositis include Gottron sign, heliotrope rash, and V or shawl sign. 52 Amyopathic dermatomyositis presents with skin findings but minimal muscle involvement, yet can involve severe ILD, highlighting the importance of skin examination in ctd-ild diagnosis. 53 Antisynthetase syndrome, defined by tRNA synthetase antibodies like anti-Jo-1, includes myositis, ILD, arthritis, fever, Raynaud phenomenon, and mechanic’s hands. 30,54
DM/PM are more common in women and Black individuals. 33,52 Environmental triggers and medications like statins may play a role. Malignancy association exists in a small percentage of cases. 55‐57 Medication review and cancer screening are important in DM/PM-ILD. ILD is frequent in DM/PM (35%-45%), sometimes preceding myositis. 33,54 Course is usually chronic, but rapid progression can occur, especially in amyopathic dermatomyositis. 30,53 Pneumothorax and pneumomediastinum have been reported, mainly in dermatomyositis. 33 Diagnosis requires high suspicion, especially in seemingly idiopathic ILD or ARDS. EMG and muscle MRI can aid diagnosis. 52
Many DM/PM-ILD patients have mildly elevated muscle enzymes. Myositis-associated autoantibodies like ANA and anti-Ro (SSA), and myositis-specific antibodies like tRNA synthetase antibodies (anti-Jo-1, anti-PL-12) are crucial for diagnosis. 55,58 Anti-SSA positivity in Jo-1 positive antisynthetase syndrome may indicate increased fibrosis and poorer treatment response. 59,60 Radiographic and pathologic findings in DM/PM-ILD are highly variable, with NSIP and organizing pneumonia (OP) being common, sometimes coexisting. 54 Ground glass opacities are frequent in fatal cases, while consolidation is more common in nonfatal cases. 61 Rapidly progressive respiratory failure and dermatomyositis are associated with poor outcome.
Corticosteroids are the mainstay of DM/PM-ILD therapy, but response varies. Combination therapy may be needed. 33,60 Cyclophosphamide is reserved for severe cases. Tacrolimus, mycophenolate mofetil, rituximab, and IV immunoglobulin have shown benefit in case series. 33,35,36,62,63 Key principles in DM/PM-ILD management include: muscle/skin disease response not predicting ILD response, amyopathic dermatomyositis ILD being more severe and less responsive, and early aggressive treatment potentially improving outcomes. 33
Sjögren Syndrome (SS) – ILD Diagnosis
Primary Sjögren syndrome (SS) is a chronic autoimmune disease affecting exocrine glands, leading to mucosal dryness. Lung involvement can occur, potentially due to glandular dysfunction and impaired mucosal defense. 64 Diagnostic criteria for SS are established. 65 Five-year survival for Sjögren-ILD is about 84%. 66 HRCT findings include ground glass opacities and honeycomb cysts. 66‐68 Multifocal cysts on HRCT raise suspicion for Sjögren-ILD.
Histopathologic patterns include NSIP, UIP, OP, and lymphocytic interstitial pneumonia (LIP). 69 LIP, a benign lymphoproliferative disease, was initially considered common but is now less prevalent, possibly due to revised diagnostic criteria for idiopathic interstitial pneumonias. 68,69 LIP typically presents radiographically with ground glass opacities and thin-walled cysts. 69 Case reports and series suggest potential benefit from corticosteroids, azathioprine, hydroxychloroquine, and rituximab in Sjögren-ILD, but clinical trials are needed to guide treatment strategies. 31,68,70,71 In summary, Sjögren-ILD presents with varied histopathology, including NSIP and LIP, and multifocal cysts on HRCT are suggestive. Sjögren-ILD can be severe, and evidence-based treatment guidelines are lacking.
Table 2. Proposed Therapies for CTD-ILD
| Medication | Doseb | Disease | Monitoring and Precautions | Refs |
|---|---|---|---|---|
| Prednisone | 0.5-1 mg/kg/d up to 60 mg/d | SSc, RA, DM, PM, SS | Monitor blood glucose level, bone mineral density, weight, and mental status. | 3, 29‐32 |
| Taper after 8-12 wk. | Doses > 20 mg/d are not advised in SSc. | |||
| If long-term use required, consider additional agents. | ||||
| Methylprednisolone | 1 g/d IV for 3 d | Acute worsening CTD-ILD | Monitor blood glucose level, bone mineral density, weight, and mental status. | 3 |
| Rule out infection before administration. | ||||
| Azathioprine | 1-2 mg/kg/d | SSc, RA, DM, PM, SS | Monitor CBC and hepatic function every 2 wk for first month, then monthly. | 3, 29, 31‐33 |
| Measure TPMT; if low, use smaller dose adjustments. | ||||
| Cyclophosphamide | 1-2 mg/kg/d po or 500-1,000 mg IV pulse every 4 wk | SSc, RA | Monitor CBC, renal function, and urinalysis at baseline, then twice monthly. | 3, 17, 32 |
| Salvage therapy because of serious toxicities. | ||||
| Mycophenolate mofetil | 1.0-1.5 g bid | SSc, RA, DM, PM | Monitor CBC weekly for first month, twice monthly second and third month, then monthly | 20, 32, 34, 35 |
| Tacrolimus | 1 mg bid | DM, PM | Monitor CBC, serum electrolytes/renal function, hepatic function, glucose level, and BP weekly for first month, twice weekly for second month, then monthly. | 3, 36 |
| Follow serum levels. | ||||
| Dose depends on trough level. Aim for trough level of 5-10 ng/mL. | ||||
| Renal toxicity occurs over time. |
DM = dermatomyositis; PM = polymyositis; RA = rheumatoid arthritis; refs = references SS = Sjögren syndrome; SSc = systemic sclerosis; TPMT = thiopurine methyltransferase. See Table 1 legend for expansion of other abbreviations.
- aThese therapies do not meet grade 1A evidence for use in CTD-ILD.*
- bAll medications are given by mouth unless otherwise indicated.*
Autoimmune-Featured Interstitial Lung Disease (AIF-ILD) Diagnosis
Evaluating for underlying CTD in ILD patients is critical, as it impacts prognosis and treatment. This evaluation identifies a subgroup with autoimmune features suggestive of CTD, but not meeting full diagnostic criteria for a specific CTD. Initially termed undifferentiated CTD, this term can be misleading as it describes a milder rheumatologic condition without typical pulmonary fibrosis in rheumatology. 72‐75 This terminological discrepancy has created confusion between pulmonologists and rheumatologists. 76
The term autoimmune-featured ILD (AIF-ILD) has been proposed to better characterize these patients. 77 Studies suggest AIF-ILD is common, representing about 32% of ILD patients undergoing comprehensive CTD evaluation. 77 AIF-ILD patients often present with multiple CTD-related symptoms and abnormal serologic tests. Clinical and demographic profiles of AIF-ILD differ from both IPF and CTD-ILD. UIP is the most common pattern in AIF-ILD, but NSIP is also observed. Survival in AIF-ILD is similar to IPF, but those with higher ANA titers (≥ 1:1,280) may have improved survival. Research indicates that 21% of idiopathic interstitial pneumonia patients have autoimmune features. 73 NSIP is more common in this group, but UIP can also occur. In HRCT-atypical IPF, Raynaud phenomenon and younger age in women were associated with better survival in the presence of autoimmune features. 73 AIF-ILD diagnostic criteria are listed in Appendix Table 1. AIF-ILD recognition is growing, but clinical, radiographic, and histopathologic characteristics remain diverse. While NSIP suggests autoimmunity, UIP can also be present in AIF-ILD and may indicate better prognosis. AIF-ILD diagnostic criteria are likely to evolve with further research. Key questions remain regarding AIF-ILD’s position within the autoimmune lung disease spectrum, disease course compared to IPF and CTD-ILD, and optimal immunosuppressive treatment strategies. Further studies are crucial to address these questions.
Conclusion
Compared to idiopathic interstitial pneumonias, CTD-ILD generally carries a more favorable prognosis and may respond to immunosuppressive therapy. Therefore, thorough evaluation for underlying CTD is essential in all ILD patients. While CTD-ILD shares autoimmune dysfunction, diverse pathogenesis results in varied clinical presentations. Table 3 summarizes key clinical pearls for ctd-ild diagnosis and management.
Table 3. Clinical Pearls for CTD-ILD
| CTD | Diagnosis | Management |
|---|---|---|
| Systemic sclerosis | Esophageal dilation on HRCT scan increases clinical suspicion. | Esophageal dysfunction and gastroesophageal reflux are common. |
| Annual screening for pulmonary hypertension is recommended by the WHO. | ||
| Rheumatoid arthritis | Consider drug-induced pneumonitis for new or worsening ILD. | Radiographic and histopathologic findings of UIP portend a worse prognosis. |
| Tobacco cessation is strongly recommended. | ||
| Dermatomyositis and polymyositis | Myositis may be subtle and present after ILD.Myositis-associated and -specific antibodies aid in diagnosis. | Early treatment with prednisone and additional immunosuppressive agents may improve outcomes. |
| Sjögren syndrome | Cysts on HRCT scan increase clinical suspicion. | Severe ILD, with UIP on HRCT scan and pathology, has been reported. |
| LIP may be less common than other histopathologic patterns. | ||
| Autoimmune-featured ILD | Comprehensive and systematic evaluation will identify these patients. | Patients with ANA titer ≥ 1:1,280 may have improved survival. |
| Seen in patients with UIP on HRCT scan and pathology. |
ANA = antinuclear antibody; LIP = lymphocytic interstitial pneumonia; UIP = usual interstitial pneumonia; WHO = World Health Organization. See Table 1 and 2 legends for expansion of other abbreviations.
Immunosuppressive therapy for systemic CTD manifestations may also benefit CTD-ILD. However, specific monitoring of pulmonary disease is crucial, as ILD course may not always mirror systemic disease activity. Immunosuppression targeted at ILD may be beneficial based on ILD severity and progression. Currently, evidence guiding CTD-ILD treatment strategies is limited. Well-designed clinical trials are urgently needed to establish optimal treatment selection and duration in CTD-ILD.
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Strek has received grants from the National Institutes of Health, ImmuneWorks, InterMune, and Gilead to conduct clinical trials in IPF. Dr Vij has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Abbreviations
AIF-ILD autoimmune-featured interstitial lung disease
ANA antinuclear antibody
CTD connective tissue disease
dc diffuse cutaneous
HRCT high-resolution CT
ILD interstitial lung disease
IPF idiopathic pulmonary fibrosis
Jo-1 histidyl transfer RNA synthetase
lc limited cutaneous
LIP lymphocytic interstitial pneumonia
NSIP nonspecific interstitial pneumonia
OP organizing pneumonia
RA rheumatoid arthritis
SSc systemic sclerosis
tRNA transfer RNA
UIP usual interstitial pneumonia
Appendix 1. Diagnostic Criteria for Connective Tissue Diseases
Systemic Sclerosis5
One major criterion or at least two minor criteria:
- Major criterion; Proximal scleroderma
- Minor criteria:
a. Sclerodactyly
b. Digital pitting scars of fingertips or loss of substance from distal finger pad
c. Bibasilar pulmonary fibrosis
Rheumatoid Arthritis38
Score of ≥ 6 points:
- Joint involvement
a. One large joint (0 points)
b. Two to 10 large joints (1 point)
c. One to three small joints (2 points)
d. Four to 10 small joints (3 points)
e. More than 10 joints (at least one small) (5 points) - Serology
a. Negative rheumatoid factor (RF) and negative anticyclic citrullinated peptide antibody (aCCP) (0 points)
b. Low positive RF or aCCP (≤ 3 times the upper limit of normal (2 points)
c. High positive RF or aCCP (> 3 times the upper limit of normal (3 points) - Acute phase reactants
a. Normal C-reactive protein and normal erythrocyte sedimentation rate (0 points)
b. Abnormal C-reactive protein or abnormal erythrocyte sedimentation rate (1 point) - Duration of symptoms
a. < 6 weeks (0 points)
b. ≥ 6 weeks (1 point)
Dermatomyositis and Polymyositis54
- Symmetric weakness of proximal muscles with or without dysphagia or respiratory muscle involvement.
- Characteristic histopathologic findings on skeletal muscle biopsy sample
- Elevation of skeletal muscle enzymes: creatine kinase, aldolase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase
- Characteristic findings on electromyography
- Dermatologic features, including
a. Heliotrope discoloration of the eyelids with periorbital edema
b. Scaly, erythematous dermatitis over the dorsa of hands, especially metacarpophalangeal and proximal interphalangeal joints
c. Involvement of the knees, elbows, medial malleoli, face, neck, and upper torso
Primary Sjögren Syndrome65
- Any four of six criteria, provided that either histopathology (#4) or autoantibodies (#6) is positive
- Any three of the following four objective criteria: ocular signs (#3), histopathology (#4), salivary gland involvement (#5), autoantibodies (#6)
- Ocular symptoms: at least one
a. Daily persistent, dry eyes > 3 months
b. Recurrent sensation of sand or gravel in the eyes
c. Use of tear substitutes > tid - Oral symptoms: at least one
a. Daily feeling of dry mouth > 3 months
b. Recurrent or persistently swollen salivary glands
c. Frequent consumption of liquid to swallow dry food - Ocular signs: at least one
a. Positive Schirmer test
b. Rose bengal score or other ocular dye score ≥ 4 - Histopathology
a. Salivary gland biopsy specimen demonstrating focal lymphocytic sialadenitis - Salivary gland involvement: at least one
a. Decreased salivary flow
b. Parotid sialography demonstrating diffuse sialectasias
c. Abnormal salivary scintigraphy - Autoantibodies
a. Antibodies to Ro (Sjögren syndrome antigen A), La (Sjögren syndrome antigen B), or both
Appendix Table 1. Autoimmune-Featured Interstitial Lung Disease—At Least One Symptom/Sign and at Least One Abnormal Serologic Test77
| Symptom/Sign | Serologic Test |
|---|---|
| Weight loss | Antinuclear antibody titer ≥ 1:160 |
| Dry eyes/dry mouth | Antidouble-stranded DNA |
| Oral ulcers | Anti-ribonucleoprotein antibody |
| Dysphagia | Anti-Smith antibody |
| Gastroesophageal reflux | Anti-Scl-70 |
| Hand ulcers | Anti-Ro antibody (anti-SSA) |
| Raynaud phenomenon | Anti-La antibody (anti-SSB) |
| Leg/foot swelling | Rheumatoid factor |
| Joint pain/swelling | Anticyclic citrullinated peptide antibody (aCCP) |
| Morning stiffness | Anti-Jo-1 antibody |
| Rash | Antineutrophil cytoplasmic antibody |
| Proximal muscle weakness | CK |
| Photosensitivity | Aldolase |
At least one symptom/sign and at least one abnormal serologic test. aCCP = anticyclic citrullinated peptide antibody; CK = creatine kinase anti-Jo-1 = antihistidyl transfer RNA synthetase; anti-Scl-70 = autoantibodies targeted against type I topoisomerase; SSA = Sjögren syndrome antigen A; SSB = Sjögren syndrome antigen B.
Footnotes
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