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CASE BASED REVIEW
Ahead of print publication  

“Spontaneous pneumomediastinum in primary Sjogren's syndrome: An uncommon manifestation”


 Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi, India

Correspondence Address:
Shibdas Chakrabarti,
Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_48_19

  Abstract 


Sjogren's syndrome (SS) is the second most common autoimmune disorder, after rheumatoid arthritis that affects predominantly middle-aged women. Pulmonary involvement in SS can manifest as airway abnormalities, interstitial lung disease (ILD), and lymphoproliferative disorders. Spontaneous pneumomediastinum has been reported in ILD associated with various connective tissue diseases, most frequently inflammatory myopathies (dermatomyositis or polymyositis). However, the occurrence of spontaneous pneumomediastinum in SS is uncommon. We report a rare occurrence of spontaneous pneumomediastinum in a patient with primary SS.

Keywords: Organizing pneumonia, pneumomediastinum, subcutaneous emphysema, systemic sclerosis



How to cite this URL:
Balasubramanian V, Chakrabarti S, Singh A, Gupta N. “Spontaneous pneumomediastinum in primary Sjogren's syndrome: An uncommon manifestation”. Indian J Rheumatol [Epub ahead of print] [cited 2019 Oct 16]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=263910




  Introduction Top


Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands and other extraglandular structures.[1] The disease may be idiopathic (primary) or secondary to other diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, polymyositis, or biliary cirrhosis. Clinical features include xerophthalmia, xerostomia, and extraglandular manifestations, including neural, renal, gastric, rheumatologic, vascular, and pulmonary.[2] Pulmonary involvement may occur before diagnosis; however, in 10% of cases, it can begin at the same time as other extrathoracic signs indicative of SS are diagnosed.[3] Patients with pulmonary involvement are found to be associated with systemic manifestations, hypergammaglobulinemia, anti-SSA and anti-SSB antibodies, lower health-related quality of life, lower physical functioning score, and higher risk of death.[4],[5],[6] Although spontaneous pneumomediastinum has been reported frequently in inflammatory myopathies (dermatomyositis, polymyositis) and other connective tissue disease (CTD)-associated interstitial lung disease (ILD),[7] the occurrence of spontaneous pneumomediastinum in SS is uncommon.[8],[9] We report a rare occurrence of spontaneous pneumomediastinum in a patient with primary SS (PSS).


  Case Report Top


A 40-year-old Asian Indian, previously healthy, nonsmoking woman was admitted to our department with complaints of low-grade fever associated with arthralgia of small joints of bilateral upper limbs, dryness of eyes and mouth, and itchy, diffuse, erythematous skin lesions involving the elbow [Figure 1]a, ankle, face, and over abdomen for 12 months. She also had complaints of progressive dyspnea and dry cough for 5 months. She consulted a general physician initially for these complaints and was treated symptomatically with a combination of medications such as analgesics, antipyretics, antihistamines, cough suppressant, and oral theophylline/bronchodilators. However, there was only partial relief of the symptoms. Subsequently, she developed worsening breathlessness, chest discomfort, swelling over the neck and anterior aspect of the chest for the last 7 days. She denied any hemoptysis, wheezing, dental caries, or difficulty in swallowing. She had no history of any comorbid illness, trauma, heavy exercise, allergy, recent travel, recent infection, immunosuppression, any intervention, or chronic drug intake, including steroids. Her occupational and family history was noncontributory. Physical examination findings revealed temperature of 99.4°F, blood pressure of 110/60 mmHg, heart rate of 98 per minute, and respiratory rate of 30 breaths per minute, with respiratory distress. There was no cyanosis, clubbing, palpable lymphadenopathy, or pedal edema. Crepitus over the face, anterior chest, and neck was present. Auscultation of the lung revealed vesicular breath sounds with bilateral basilar crackles. Arterial blood gas analysis showed hypoxemic respiratory failure (pH: 7.43, paCO2: 36 mmHg, paO2: 58 mmHg, bicarbonate: 22.5, and SaO2: 88%). Pneumomediastinum was observed on chest radiograph, without evidence of pneumothorax [Figure 1]b. High-resolution computed tomogram (HRCT) of the thorax confirmed bilateral subpleural consolidation associated with pneumomediastinum and subcutaneous emphysema [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f. The patient was initially managed conservatively with oxygen inhalation and analgesics. Empirical antibiotics (piperacillin + tazobactam and clindamycin) were also started considering infective etiology. All routine investigations, including peripheral smear for blood picture, were normal. Erythrocyte sedimentation rate and C-reactive protein were elevated (64 mm/1st h and 56.2 mg/dl, respectively). Lipid and thyroid profiles were within normal limits. Echocardiography and ultrasound of the abdomen were normal. Serology for HIV, HBsAg, and hepatitis C was negative. Mantoux test revealed no induration. Urinalysis was normal. Blood and urine cultures were sterile. The patient was unable to produce sputum, and fiberoptic bronchoscopy was performed subsequently. Bronchoscopic findings were unremarkable, and bronchoalveolar lavage was negative for any infection or malignancy. Transbronchial lung biopsy (TBLB) was deferred in view of acute hypoxemic respiratory failure and pneumomediastinum. Pneumomediastinum and subcutaneous emphysema gradually resolved after 2 weeks of hospital stay. Resolution of pneumomediastinum was assessed with serial chest X-rays. No repeat CT scan performed to minimize radiation exposure. However, there was only partial response to therapy, and she continued to have breathlessness and cough. Consolidation persisted on serial radiological imaging performed 3 weeks following admission. Autoantibodies profile was also sent in view of strong clinical suspicion of underlying CTD. Antinuclear antibody testing was positive with titer 1/640 and nucleus homogenous pattern on immunofluorescence. Qualitative extractable nuclear antigen testing suggested strong positivity for antibody against SSA/Ro and negativity for SSB. Antibodies against other antigens such as U1-RNP, Scl-70, PM Scl-100, Jo-1, MDA-5, centromere, and dsDNA were also not detected. C3 and C4 complement components were normal. Anti-neutrophil cytoplasmic antibodies, angiotensin-converting enzyme, creatine phosphokinase, antiphospholipid antibodies, rheumatoid factor, and anti-CCP were also negative. Schirmer's test results in both eyes were <5 mm in 5 min (normal >15 mm), and ocular staining score was >3. Histopathology of minor salivary gland biopsy from lower lip revealed subepithelial lymphocytic infiltrate and edema [Figure 3]a. Focal lymphocytic aggregates were also observed, but no comment on focus score was made. All these features confirmed the diagnosis of PSS. ILD with organizing pneumonia (OP) was then considered as differential diagnosis in view of background of diagnosed CTD. Subsequently, pulmonary function test (PFT) was performed on day 27 following admission that revealed moderate restrictive ventilatory defect with severely impaired diffusion. Definitive diagnosis of ILD by histopathology was planned by multidisciplinary discussion team comprising radiologist, pathologist, and rheumatologist. TBLB was performed subsequently and biopsy specimen for histopathology revealed alveolar spaces filled intra-alveolar projections made up of spindle-to ovoid cells with eosinophilic stroma and also focal septal thickening with few mononuclear cells consistent with OP [Figure 3]b, [Figure 3]c. The patient was started on tablet prednisolone at a dose of 0.5 mg/kg/day (30 mg daily as body weight of 60 kg) and other supportive measures. Final diagnosis of OP associated with PSS was established. She was discharged under regular follow-up and currently doing well, without any recurrence.
Figure 1: (a) Diffuse erythematous skin lesions involving the elbow. (b) Chest X-ray showing pneumomediastinum (black horizontal arrows) without pneumothorax

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Figure 2: (a-f) High-resolution computed tomogram thorax showing bilateral subpleural and band-like consolidation (black horizontal arrows) likely organizing pneumonia with pneumomediastinum (white horizontal arrows) and subcutaneous emphysema (white vertical arrowhead)

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Figure 3: (a) Histopathology of minor salivary gland biopsy from lower lip revealed subepithelial lymphocytic infiltrate (black horizontal arrow) and edema (arrowhead) (H and E stain, ×40). (b and c) Transbronchial lung biopsy for histopathology showing alveolar spaces filled intra-alveolar projections or deposition (black horizontal arrows) made up of spindle-to-ovoid cells with eosinophilic stroma (H and E stain, ×100)

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  Discussion Top


SS is the second most common autoimmune disease after rheumatoid arthritis. Hypothesized etiopathogenesis of SS involves complex interplay of environmental factors such as viruses (cytomegalovirus, HIV, human T-cell leukemia virus, and hepatitis C virus), solvents, genetic predisposition, and hormonal deregulation, which leads to an initial glandular inflammation called autoimmune epithelitis and a deregulated immune response.[10],[11] The syndrome is characterized by lymphocytic infiltration of the exocrine glands and other extraglandular organs such as lungs, thyroids, kidneys, or hepatobiliary tract and in <5% of cases can experience a malignant transformation into non-Hodgkin's lymphoma.[1] SS can present as a separate entity (PSS), or it can be associated with other connective tissue disorders such as rheumatoid arthritis (secondary SS).[2] According to the American College of Rheumatology,[12] SS can be diagnosed if at least two of the three following objective feature are met which include positive serum anti-SSA/Ro and/or anti-SSB/La (or positive rheumatoid factor and anti-nuclear antibodies at a dilution >1/320), minor salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score >1 per 4 mm[2], and keratoconjunctivitis sicca with ocular staining score >3. In the present case, since the patient fulfilled all the three diagnostic criteria and no features supportive of CTD and lymphoproliferative disorder could be demonstrated, a diagnosis of PSS was made. Pulmonary involvement in SS can manifest as airway abnormalities, interstitial pneumonia, and lymphoproliferative disorders, with cough being the most symptom.[13] Among the interstitial lung disorders, nonspecific interstitial pneumonia is the most common presentation (45%) followed by usual interstitial pneumonia (16%), lymphocytic interstitial pneumonia (15%), and OP (11%).[14] In this patient, the HRCT picture was suggestive of OP pattern. Among all CTDs, pneumomediastinum is most commonly associated with inflammatory myositis, with a prevalence of 8.3%, and is associated with poor prognosis.[15] Though infrequent, pneumomediastinum is also seen in other CTDs such as systemic lupus erythematosus,[16] rheumatoid arthritis,[17] and systemic sclerosis.[18] Various theories have been attributed to the occurrence of spontaneous pneumomediastinum in inflammatory myositis which includes rupture of the subpleural or paracardiac blebs due to marked increase in intra-alveolar pressure,[19] vasculitis induced,[15] or alveolar weakening due to steroid treatment.[20] However, spontaneous pneumomediastinum in PSS is extremely rare. To the best of our knowledge, this is the third case report in the literature to showing occurrence of spontaneous pneumomediastinum in PSS [Table 1]. In our case, there was no evidence of bleb, bullae, cavitary or cystic lesion, and also pneumothorax on HRCT thorax. PFT was also performed once pneumomediastinum completely resolved, as few have reported occurrence of pneumomediastinum after performing the procedure.[7] The duration for performing PFT after resolution of pneumomediastinum is not documented although it can be performed after 2 weeks in a patient with healed pneumothorax.[21] Pneumomediastinum is a benign entity of little clinical importance, and treatment is directed toward symptom relief. Management involves mere observation with control of pain with analgesics, suppression of cough with antitussives, and administration of oxygen.[22] This patient was managed conservatively with oxygen and limitation of exertion. For the underlying OP associated with PSS, she was treated with steroids. Pneumomediastinum resolved and the patient was discharged on day 30 of hospital admission. She was also referred to rheumatologist for further management. Tapering of steroids was initiated after 1 month of discharge as there was clinical improvement with normal oxygenation and no deterioration on chest X-ray. CT scan thorax was planned after 3 months following initiation of steroids. However, we could not ascertain the response subsequently as patient was lost to follow-up.
Table 1: Comparison of our case with prior case report of Sjogren's syndrome with spontaneous pneumomediastinum

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Our case demonstrates a rare complication of spontaneous pneumomediastinum in PSS, an occurrence which is yet to be extensively documented in the literature in the near future.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kokosi M, Riemer EC, Highland KB. Pulmonary involvement in Sjögren syndrome. Clin Chest Med 2010;31:489-500.  Back to cited text no. 1
    
2.
Tincani A, Andreoli L, Cavazzana I, Doria A, Favero M, Fenini MG, et al. Novel aspects of Sjögren's syndrome in 2012. BMC Med 2013;11:93.  Back to cited text no. 2
    
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Ramos-Casals M, Solans R, Rosas J, Camps MT, Gil A, Del Pino-Montes J, et al. Primary Sjögren syndrome in Spain: Clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 2008;87:210-9.  Back to cited text no. 3
    
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García-Carrasco M, Ramos-Casals M, Rosas J, Pallarés L, Calvo-Alen J, Cervera R, et al. Primary Sjögren's syndrome: Clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore) 2002;81:270-80.  Back to cited text no. 4
    
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Palm O, Garen T, Berge Enger T, Jensen JL, Lund MB, Aaløkken TM, et al. Clinical pulmonary involvement in primary Sjögren's syndrome: Prevalence, quality of life and mortality – A retrospective study based on registry data. Rheumatology (Oxford) 2013;52:173-9.  Back to cited text no. 5
    
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Le Goff B, Chérin P, Cantagrel A, Gayraud M, Hachulla E, Laborde F, et al. Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis. Arthritis Rheum 2009;61:108-18.  Back to cited text no. 7
    
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Kagihara JM, Kitamura CY, Evans SJ. Sjögren's, steroids, and subcutaneous emphysema. Hawaii J Med Public Health 2015;74:50.  Back to cited text no. 8
    
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Ziaee S, Weddington CM, Colbert C. Spontaneous pneumomediastinum, retroperitoneal air and subcutaneous emphysema in patient with connective tissue disease associated interstitial lung disease. Cases Med Res J 2018;1:1-4.  Back to cited text no. 9
    
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Martel C, Jauberteau MO, Vidal E, Fauchais AL. Pathophysiology of primary Sjögren's syndrome. Rev Med Interne 2014;35:524-30.  Back to cited text no. 10
    
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Tapinos NI, Polihronis M, Tzioufas AG, Moutsopoulos HM. Sjögren's syndrome. Autoimmune epithelitis. Adv Exp Med Biol 1999;455:127-34.  Back to cited text no. 11
    
12.
Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. American College of Rheumatology classification criteria for Sjögren's syndrome: A data-driven, expert consensus approach in the Sjögren's international collaborative clinical alliance cohort. Arthritis Care Res (Hoboken) 2012;64:475-87.  Back to cited text no. 12
    
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Papiris SA, Maniati M, Constantopoulos SH, Roussos C, Moutsopoulos HM, Skopouli FN. Lung involvement in primary Sjögren's syndrome is mainly related to the small airway disease. Ann Rheum Dis 1999;58:61-4.  Back to cited text no. 13
    
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Manuel RC, Pilar BZ, Raphaèle S, Hendrika B, Simon JB, Thomas D, et al. Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS task force recommendations for articular, cutaneous, pulmonary and renal involvements. Rheumatology (Oxford) 2017;56:1245.  Back to cited text no. 14
    
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Kono H, Inokuma S, Nakayama H, Suzuki M. Pneumomediastinum in dermatomyositis: Association with cutaneous vasculopathy. Ann Rheum Dis 2000;59:372-6.  Back to cited text no. 15
    
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Paira SO, Roverano S. Bilateral pneumothorax and mediastinal emphysema in systemic lupus erythematosus. Clin Rheumatol 1992;11:571-3.  Back to cited text no. 16
    
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Dikensoy O, Bayram N, Bingol A, Filiz A. Bronchiolitis obliterans in a case of juvenile rheumatoid arthritis presented with pneumomediastinum. Respiration 2002;69:100-2.  Back to cited text no. 17
    
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Teixeira Moreira Almeida Mdo S, Dias LT, Fernandes SJ, Almeida JV. Spontaneous pneumomediastinum and subcutaneous emphysema in systemic sclerosis. Rheumatol Int 2007;27:675-7.  Back to cited text no. 18
    
19.
Tang R, Millett CR, Green JJ. Amyopathic dermatomyositis complicated by pneumomediastinum. J Clin Aesthet Dermatol 2013;6:40-3.  Back to cited text no. 19
    
20.
Kishi K, Kashiwabara K, Narushima K, Sarashina G, Kobayashi K, Yagyu H, et al. Mixed connective tissue disease-associated interstitial pneumonia complicated by pneumomediastinum during prednisolone therapy. Nihon Kokyuki Gakkai Zasshi 2000;38:480-4.  Back to cited text no. 20
    
21.
MacDuff A, Arnold A, Harvey J, BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010. Thorax 2010;65 Suppl 2:ii18-31.  Back to cited text no. 21
    
22.
Kouritas VK, Papagiannopoulos K, Lazaridis G, Baka S, Mpoukovinas I, Karavasilis V, et al. Pneumomediastinum. J Thorac Dis 2015;7:S44-9.  Back to cited text no. 22
    


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