Organising pneumonia in Rhupus syndrome

Abstract

Interstitial lung disease (ILD) is seen in 17% of patients with Rhupus syndrome. Organising pneumonia (OP), a subtype of connective tissue disease-associated ILD, is rare but associated with good outcomes. Here, we present a patient with Rhupus who developed OP.

Background

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are two distinct autoimmune diseases with different clinical features involving various organs. Rhupus syndrome is a term used to describe patients with RA and SLE overlap. This is a rare syndrome with an estimated prevalence rate of 0.09%.¹

Interstitial lung disease (ILD) is seen in 17.9% of patients with Rhupus.² The most common patterns of ILD observed in the rheumatologic diseases include non-specific interstitial pneumonia, usual interstitial pneumonia (UIP), organising pneumonia (OP), lymphocytic interstitial pneumonia, acute interstitial pneumonia/diffuse alveolar damage.³ OP is a relatively uncommon subtype. However, this is associated with lower relapse rates, lower mortality rates and significant symptomatic improvement with treatment.

Here, we present a 57-year-old woman with Rhupus syndrome with OP at symptom onset.

Case presentation

A 57-year-old woman, daily wage labourer working in construction industry, presented with low-grade intermittent fever and polyarthritis for 2 months. Joint pain started in the proximal interphalangeal (PIP) joints and progressed to involve the metacarpophalangeal joints, bilateral wrists, elbows, shoulders, hips, knees, ankles and the metatarsophalangeal joints of the foot. Joint pain was associated with early morning stiffness that last for 30–60 min.

She reported progressively worsening dyspnoea for 2 months (Modified Medical Research Council Grade 1–Grade 3). She also had history of hair loss, cough with small amount of whitish expectoration and unquantifiable loss of weight and appetite. There was history of occupational exposure to sand for 20 years.

There was no history of skin rashes/tightness, photosensitivity, oral ulcers, Raynaud’s phenomenon, dry eyes, reduced urine output, palpitations, orthopnoea, paroxysmal nocturnal dyspnoea or bleeding manifestations. She denied history of prior treatment for her symptoms.

On examination, pallor, alopecia and bilateral axillary lymphadenopathy were present. Pulse rate and blood pressure were 64/min and 100/60 mm Hg, respectively. Respiratory rate at presentation was 20 breaths/min. Temperature was 37.8°C. Joint deformities included flexion of left fifth, right second and fifth distal interphalangeal joints and swelling of all PIP joints of both hands and genu varus deformity of both knees. Respiratory system examination revealed coarse crepitations with bronchial breath sounds in bilateral infrascapular and infraaxillary region. Dull percussion note was heard in the above areas. Rest of the systemic examination was unremarkable.

Investigations

On initial evaluation she had microcytic anaemia with elevated lactate dehydrogenase (909 U/L) with direct Coombs test 2+ (haemolytic anaemia). She had neutrophil predominant leucocytosis (15.4×10⁹/L) with elevated platelets (523×10⁹/L). Rheumatoid factor was elevated (116 IU/mL) along with inflammatory marker erythrocyte sedimentation rate (65 mm) and C-reactive protein (78.8 mg/L). However, her anti-cyclic citrullinated peptide (CCP) ELISA was within normal range (7 U/mL) was negative (table 1).

Table 1.

Investigations

Haemoglobin (g/L)	80	ESR (mm)	65
Mean corpuscular volume (fL)	70.0	CRP (mg/dL)	78.8
Lactate dehydrogenase (U/L)	909	Rheumatoid factor (IU/mL)	116
WBC counts (/L)	15.4×109 (N-89)	Anti-CCP (RU/mL)	7
Platelets (/L)	523×109	ANA	2+
Sodium/potassium (mmol/L)	138/4.3	C3/C4	88.5/15/8
Calcium/phosphate (mg/dL)	7.56/3.7	Direct Coombs test	2+
Urea/creatinine (mg/dL)	40/0.61	DS DNA(IU/mL)	1
Liver function test	0.32/0.08/6.9/1.9/32/21/85	Lupus anticoagulant	Negative
PT/INR/APTT	11.5/1.06/39.2	Anti-U1RNP (RU/mL)	3
24-hour protein (mg/day)	113	Anti-scl-70 (RU/mL)	7

ANA, Antinuclear Antibody; APTT, activated partial thromboplastin time; ESR, erythrocyte sedimentation rate; INR, International Normalized Ratio; PT, prothrombin time; U1RNP, U1 ribonucleoprotein.

Generalised periarticular osteopaenia and soft tissue swelling at PIP joints in multiple fingers were noted on hand radiographs (figure 1). Chest X-ray showed heterogenous opacities in bilateral lower zones. CT scan of thorax showed multiple foci of subpleural and peribronchovascular consolidation (figure 2). ECG was normal, whereas echocardiogram showed a small pericardial effusion.

Figure 1.

(A) Frontal radiograph of hands shows generalised periarticular osteopaenia (black arrow) and soft tissue swelling at proximal interphalangeal joints in multiple fingers (short arrow). (B) Frontal radiograph of bilateral knee joints show well defined lucency with surrounding sclerotic rim, suggestive of osteochondral defect (black arrow) in the inferomedial aspect of medial condyle of right femur.

Figure 2.

Axial (A) and coronal (B) high resolution CT study of the thorax shows multiple foci of subpleural consolidation (single arrow) and peribronchovascular consolidation (double arrows).

Differential diagnosis

The following differential diagnoses were considered for her respiratory symptoms—RA/SLE-associated ILD, disseminated tuberculosis (pulmonary and lymph node tuberculosis), silicosis, sarcoidosis, OP and lymphangitic carcinomatosis.

She fulfilled American College of Rheumatology—European league against Rheumatism criteria for diagnosis of RA (joint involvement—5; serology—2; acute phase reactants—1 and symptoms duration—1) with Disease Activity Score of 6.05.

She also fulfilled Systemic Lupus International Collaborating Clinic criteria for diagnosis of SLE (clinical criteria—serositis, joint disease, non-scarring alopecia, haemolytic anaemia; immunological criteria—low C3, antinuclear antibody (ANA) positive with SLE Disease Activity Index score of 9. Hence, she was diagnosed to have Rhupus syndrome.

CT scan of thorax showed multiple foci of subpleural and peribronchovascular consolidation suggestive of OP (figure 2).

She underwent bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial lung biopsy. Tests for infective aetiology (Ziehl-Neelsen stain, Mycobacteria Growth Indicator Tube, Gene Xpert PCR for Mycobacterium tuberculosis, Gram stain and fungal culture) were negative in sputum and BAL specimens. Her lung biopsy showed intra-alveolar fibroblastic plugs, macrophages and type II pneumocyte hyperplasia, consistent with OP (figure 3).

Figure 3.

Photomicrograph depicting lung parenchyma with many intra-alveolar fibroblastic plugs (black arrows), H&E, 100×.

Left axillary lymph node biopsy showed reactive changes, without any features of tuberculosis or malignancy. During her hospital stay, she developed pneumothorax following bronchoscopy which resolved with 100% oxygen administration.

Treatment

She was initiated on oral prednisolone (dose of 1 mg/kg) for the OP. She was also initiated on disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, sulphasalazine and azathioprine) for her inflammatory polyarthritis.

Outcome and follow-up

She started showing signs of clinical improvement after being initiated on steroids and DMARDs. She was afebrile and her dyspnoea and arthralgia gradually resolved. She was able to ambulate freely and able to do all her activities of daily living. She was discharged after 3 weeks of hospitalisation with an advice to follow-up after 1 month but she did not come back for follow-up despite multiple telephonic requests.

Discussion

Rhupus is a rare syndrome that comprises of patients who fulfil diagnostic criteria for RA and SLE. In a retrospective study by Li et al that included 56 Rhupus patients, median age at symptom onset was 45.5 years, with 84% having initial symptoms similar to RA.² This is similar to our patient’s clinical presentation. All Rhupus patients had symmetrical inflammatory arthritis with erosions on radiographs. Renal and neurologic involvements were less frequent in Rhupus patients than in the control group with SLE (p value—0.002 and 0.015, respectively). 17.9% patients with Rhupus had ILD.

Lee et al found that OP accounted for 11% (2/18) of RA-associated ILD. UIP was the most common subtype (55%, 10/18). Both patients with OP were women and current smokers. Duration of respiratory symptoms at diagnosis was 1.5±0.7 months. Both were treated with corticosteroids and had improvement in pulmonary function tests and clinical symptoms at follow-up after 6 years.⁴

The association of OP and Rhupus is rare. Sarkar and Saha⁵ reported a 23-year-old Rhupus patient with fever, breathlessness and cough. She was diagnosed to have acute pneumonitis based on high resolution computed tomography (HRCT) scan features of consolidation in multiple areas in both lungs, bilateral small pleural effusions and lack of response to antibiotic therapy. She was managed with oral prednisolone and DMARD with which she improved.

HRCT features in OP include ground glass opacities, consolidation and peribronchovascular opacities. Distribution of lesions is usually bilateral, with the middle and lower lobes commonly involved.⁶

CT scan of the thorax can provide invaluable information that strongly supports a specific diagnosis and may be diagnostic in certain types of ILD like UIP such that further testing with bronchoscopy or surgical lung biopsy is not required.⁷ But in case of OP type of ILD, the radiological features of HRCT have not been described to be diagnostic. Hence, warranting need for lung biopsy for confirmation.⁷

It is also important to obtain a histological diagnosis via lung biopsy in order to determine ILD subtype and prognosticate the patient. Lung biopsy also plays a vital role in ruling out other causes like infections and chronic eosinophilic pneumonia.⁸

Among RA associated ILD, OP has better prognosis as compared with UIP. Mori et al found better response in patients with OP as compared with UIP after treatment with corticosteroids. Second line agents like azathioprine and mycophenolate mofetil may need to be added in addition to corticosteroids in patient with steroid-resistant ILD. However, most patients with OP have good outcomes with corticosteroids alone.⁹

Learning points.

• Though rare, organising pneumonia (OP) can occur in patients with rheumatoid arthritis and systemic lupus erythematosus overlap syndrome (Rhupus).

• Histological diagnosis via lung biopsy should be obtained to rule out infectious aetiologies and chronic eosinophilic pneumonia.

• OP has better prognosis than other forms of connective tissue disease-related interstitial lung disease.