Rare case of Sjögren’s syndrome antibody (SSA-Ro52kDA)-associated interstitial lung disease and myositis with pipe stem capillaries

Abstract

Necrotising myopathy with pipestem capillaries is a distinct form of inflammatory myopathy exhibiting only sparse inflammation on biopsy, with clinical presentation and histopathological profile entirely different from dermatomyositis, polymyositis or inclusion body myositis. A 51-year-old non-diabetic man presents with progressively worsening shortness of breath and myalgias with only mild proximal muscle weakness and elevated serum creatine kinase. Autoimmune workup, ordered after ruling out infectious and cardiac aetiologies, returned positive for Sjögren’s syndrome antibody (SSA/Ro-52). Lung imaging and biopsy were suggestive of cryptogenic organising pneumonia and muscle biopsy showed myositis with pipestem capillaries and abnormal deposition of membrane attack complex with only sparse inflammation. The patient received high-dose steroids, mycophenolate mofetil, intravenous immunoglobulin and rituximab with improvement in muscle symptoms. However, his pulmonary findings progressed, requiring evaluation for a lung transplant. This case emphasises the need for further research to better understand this disease entity and improve mortality and morbidity in these patients.

Background

Necrotising myopathy with pipestem capillaries is a rare form of inflammatory myopathy with minimal cellular infiltration.¹ It has varied clinical presentations without any clear association with any particular disease entity. Given there have only been a handful of cases reported in literature, little is known about treatment outcomes and prognosis in these patients.

Case presentation

A 51-year-old African-American man with a history of hypertension was admitted to the hospital with a 2-month history of dry cough associated with pleuritic chest pain, progressively worsening exertional dyspnoea and myalgia primarily involving proximal upper extremities. The patient also had dry eyes, for which he was evaluated by ophthalmology, and it was deemed that findings were not suggestive of Sjögren’s syndrome. He denied any recent history of dry mouth, gland enlargement, dental caries, fever, rash, joint pains, Raynaud’s phenomenon, dysphagia, dysarthria or constitutional symptoms. Prior to this presentation, he was treated with a 2-week course of antibiotics for presumed pneumonia as an outpatient, based on chest X-ray showing bilateral pneumonia, but had no improvement of symptoms. He did not have any significant past surgical history, had no known drug allergies and denied any toxic habits. The patient was born and raised in Dominican Republic and had been living in the USA for the past 6 years. The patient was a construction worker by occupation, with exposure to dust and had no other potential occupational exposures. He did not have any history of prior statin use and was not taking any medications at the time of presentation. The patient denied any family history of autoimmune diseases or myopathies.

On physical examination, the patient was noted to be afebrile and tachycardic to 111 beats/min. His oxygen saturation on room air was 95% at rest but decreased to 86% on ambulating a few feet. Lung examination was remarkable for bibasilar crackles and neurological examination revealed proximal muscle strength of 4/5 in bilateral upper and lower extremities and normal strength in distal muscle groups. Nailfold capillary exam, as well as skin examination, was normal.

Initial laboratory results revealed mild eosinophilia (15%, Abs: 1100 eosinophils/uL), normal erythrocyte sedimentation rate (ESR), mildly elevated c-reactive protein (CRP: 2 mg/dL) and transaminitis (aspartate transaminase/alanine transaminase, AST/ALT: 177/170). Cardiac enzymes were elevated (creatine kinase, CK:4618 U/L; Troponin T: 0.17 ng/mL), however, his ECG did not show any ischaemic changes and echocardiogram revealed no regional wall motion abnormalities. ProB-type natriuretic peptide (ProBNP) was also normal, helping to exclude acute coronary syndrome and heart failure. Chest X-ray revealed bibasilar infiltrates compatible with pneumonia and a subsequent CT chest showed multilobar ground glass infiltrates with patchy opacities in bilateral lower lobes. Given the absence of fever/chills/leukocytosis and persistent symptoms despite a course of antibiotics, suspicion for bacterial pneumonia was low.

Further evaluation by bronchoscopy revealed 45% eosinophils (Abs: 301 eosinophils/uL) in the bronchoalveolar lavage (BAL) fluid. Extensive workup was done to evaluate for potential aetiologies of eosinophilia and eosinophilic pneumonia including stool, serum and BAL fluid testing for fungal infections, ova and parasites (table 1) which came back negative. Multiple COVID-19 PCR tests done during hospitalisation and in the outpatient setting were negative. Patient also did not have a history of asthma like symptoms; his shortness of breath was primarily exertional. Transbronchial biopsy done at the time showed alveolated lung parenchyma with organising pneumonia. Pulmonary function tests (PFTs) were compatible with restrictive lung disease.

Table 1.

Eosinophilia workup*

Parasite			Fungal
Serum	Stool	Bronchoalveolar lavage (BAL)	Serum	BAL
Strongyloides Trichinella Schistosoma Toxoplasma Toxocara	Ova and parasite	Ova and parasite	Coccidioides Aspergillus Histoplasma	Fungal culture

*All tests returned negative.

The mild proximal muscle weakness, elevated CK along with above mentioned biopsy and radiographic lung findings raised concern for an inflammatory myopathy associated with interstitial lung disease (ILD). Therefore, further investigation to evaluate for autoimmune rheumatic aetiologies was initiated. His antinuclear antibody test was positive with a titre of 1:640 along with high positive SSA/Ro-52 antibodies. HMGCR Ab was negative, and Aldolase was elevated (42.8 U/L). Remaining myositis panel was negative.

MRI of the thighs revealed bilateral muscle oedema most pronounced in the bilateral gluteal regions, quadratus femoris and vastus lateralis. Electromyography (EMG) of right iliopsoas muscle showed 2+ sharp motor unit action potential with a low normal amplitude and early recruitment, suggestive of myositis. Skeletal muscle biopsy showed the presence of chronic microangiopathic changes in the form of ‘pipestem’ capillaries and abnormal deposition of membrane attack complex (MAC) C5b-9 involving endomysial capillary blood vessels (figure 1). Scattered rare necrotic myofibres were also present suggestive of a necrotising myopathy.

Figure 1.

Skeletal muscle biopsy showing the presence of (A) chronic microangiopathic change in the form of ‘pipestem’ changes (arrow) and (B) abnormal deposition of MAC C5b-9 involving endomysial capillary blood vessels (star). Scattered rare necrotic myofibres are also identified. MAC, membrane attack complex.

The patient was started on intravenous steroids during his hospitalisation and prior to being discharged home was transitioned to 1 mg/kg of prednisone daily.

Outcome and follow-up

On subsequent outpatient follow-up with rheumatology, the patient reported only minimal improvement in his shortness of breath, myalgias and muscle weakness despite high dose steroids. Within 3 weeks, he was started on mycophenolate mofetil as a steroid sparing agent which was uptitrated to a full dose of 3 gm daily over the next 4 weeks. A slow steroid taper was initiated, and the patient is currently taking prednisone 5 mg daily. Despite being on a full dose of mycophenolate mofetil for more than 3 months, he did not have any significant improvement in his symptoms. His CK levels remained elevated and repeat CT chest revealed persistent bilateral infiltrates.

A trial of intravenous immunoglobulin therapy (2 gm/kg body weight) was initiated but was stopped after 5 months as there was no significant improvement. The patient reported worsening pulmonary symptoms, and with declining diffusing capacity for carbon monoxide on PFTs, a chest CT scan was repeated, which showed interval progression of his ILD (figures 2 and 3). Rituximab was added to his immunosuppressive regimen, after which patient did report some improvement of muscular symptoms and CK decreased from 2609 U/L to 1136 U/L. However, the patient’s eosinophilia did not resolve completely with steroids and immunosuppression and pulmonary symptoms persisted. The patient was referred for lung transplant, was deemed to be a candidate and is currently undergoing testing and optimisation for lung transplant.

Figure 2.

CT chest at initial presentation showing multilobar ground glass infiltrates with patchy opacities in bilateral lower lobes.

Figure 3.

CT chest 18 months after presentation showing interval progression of interstitial lung disease.

To our knowledge, this is the first reported case of SSA antibody associated necrotising myositis with pipestem capillaries and ILD (cryptogenic organising pneumonia).

Discussion

Inflammatory myopathies are a group of autoimmune diseases usually presenting with muscle weakness, elevated muscle enzymes and abnormal EMG. Muscle biopsy usually reveals perimysial/perivascular inflammation. In addition to the muscle involvement, patients can frequently have associated ILD, arthritis and skin manifestations.¹

In 1991, Emslie-Smith and Engel identified three cases with a unique form of necrotising autoimmune myopathy with distinct histopathological findings of thick hyalinised vessels which they labelled as ‘pipestem capillaries’ along with abnormal deposition of complement MAC, decreased capillary density, and only sparse inflammation.² Since then, only a handful of case reports have been reported with similar histopathological findings, all of which have had varied presentations with no clear unifying systemic illness. Reported associations have included connective tissue disorders, neoplasms, cerebral infarcts and vasculitis.^2–7

In contrast to other inflammatory myopathies which manifest primarily as muscle weakness, myalgia was noted to be a predominant feature in most of these patients, as was seen in our case as well. Also, CK is usually only 5–10 fold increased, similar to what was observed in our case, however, the presence of autoantibodies varied.³ Eosinophilia was not reported in any of the cases, however our patient had eosinophilia, both in serum and BAL samples, the significance of which remains unclear.

Our patient also had positive SSA/Ro-52 antibodies, which was only reported in the case published by Acciavatti et al; however, their patient presented as a paraneoplastic syndrome secondary to underlying adenocarcinoma of lung and the patient did not have ILD.⁴ Peripheral or central nervous system involvement has been reported in many cases, manifesting as neuropathy or vasculitis like presentation respectively.^2–6 This patient, fortunately, does not have any such manifestations until, but is being monitored closely as the case described by Authier et al developed CNS manifestations 4 years after the initial presentation.⁷

Emslie-Smith et al and Authier et al both published a case in which the patient developed cerebral infarcts (one secondary to CNS vasculitis and the other likely due to the same). However, while Authier et al’s patient showed a good response to just steroid therapy, Emslie-Smith et al’s patient proved to be more resistant, and required cyclophosphamide and intravenous immunoglobulin infusions to achieve a clinical response.^{2 7} Cases published by Reimann et al and Patil et al also required escalation of therapy to cyclophosphamide and/or intravenous immunoglobulin for better clinical response.^{3 6} This was similar to our patient who showed only minimal response to steroid therapy, requiring escalation of treatment to mycophenolate mofetil, intravenous immunoglobulin infusions and rituximab. As our patient presented during the COVID-19 pandemic, there were concerns regarding cyclophosphamide use leading to worse outcomes in the event that the patient contracted COVID-19 while on therapy. Hence, the decision was made to initiate rituximab instead of cyclophosphamide due to its superior safety profile.^{3 6} Mycophenolate and rituximab were not initiated in any of the previously published cases.

Muscle biopsies reported in the published cases showed necrotising myopathy with sparse inflammation and microangiopathy with hyalinised vessels showing deposition of MAC and periodic acid–Schiff (PAS) positive material (pipestem capillaries) and major histocompatibility complex I expression on necrotic fibres.^2–7 Our patient had all the above findings apart from PAS negative vessel wall deposits.

This case highlights the challenges faced in treating patients with necrotising myopathy, as seen in our patient who clinically worsened despite aggressive immunosuppression.

So far, there are no published cases of SSA positive necrotising myopathy with pipestem capillaries with associated ILD. Our case is unique in this regard.

Patient’s perspective.

Prior to my initial hospitalisation I was highly functional and was able to carry heavy loads while working in construction. However ever since this illness I have not been able to carry out these activities and feel that my sickness has significantly impacted my life. I hope to regain some of my prior functional status after receiving a lung transplant. I would like my case to be published as this may have the benefit of helping guide the management of others who have a similar illness.

Learning points.

• Persistent shortness of breath with chest X-ray findings suggestive of pneumonia in the absence of systemic symptoms of infection warrant evaluation for alternative aetiologies such as interstitial lung disease.

• Elevated creatine kinase in range of 5000 U/L in the absence of any cardiac aetiology should raise suspicion for inflammatory myopathy in the appropriate clinical context.

• Patients with myositis with pipestem capillaries are difficult to treat and respond poorly to conventional therapies and further research is needed to elucidate the pathophysiology of this disease entity which can be helpful in managing these patients in the future.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).