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On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
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KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

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Dr. Anuradha
On Jan 2020

Important Notice

Case report
Year : 2022 | Month : June | Volume : 16 | Issue : 6 | Page : OD14 - OD16 Full Version

A Case of Acute Breathlessness in Systemic Lupus Erythematosus: A Devastating Complication

Published: June 1, 2022 | DOI:
Varsha Bhatt, Kavya Koneru, Abhishek Zanwar, Manaswini Edara, Anusha Vattikuti

1. Professor, Department of General Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 2. Postgraduate Resident, Department of General Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 3. Consultant, Department of Rheumatology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 4. Postgraduate Resident, Department of General Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 5. Postgraduate Resident, Department of General Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India.

Correspondence Address :
Dr. Kavya Koneru,
D4-806, Mahendra Antheia Society Pimpri, Pune, Maharashtra, India.


Diffuse Alveolar Haemorrhage (DAH) is a severe respiratory complication of Systemic Lupus Erythematosus (SLE) and is associated with high mortality. A drop in blood haemoglobin, dyspnoea, haemoptysis, diffuse infiltrates on chest imaging indicate this devastating diagnosis. The DAH is rare in SLE, even rarer in the early months in an undiagnosed patient. Defective phagocytosis, immune complexes, depletion of complement, autoantibodies is the etiology. Immune complex induced alveolar capillaritis is the cause of DAH. This report was about a 28-year-old female, who presented with acute worsening dyspnoea on a background history of inflammatory joint pain, digital gangrene, alopecia, oral ulcers, and Raynaud’s phenomenon. She was subsequently diagnosed as SLE with DAH. This case was rare as she presented with DAH in the early months of her disease. Patient was started on high dose steroid, cyclophosphamide, and plasmapheresis, but succumbed on day 14 of admission due to high disease activity and respiratory failure. The DAH carries very high mortality rate even in best centres even when diagnosed early.


Diffuse alveolar haemorrhage, Immune complex, Steroid

Case Report

A 28-year-old female, presented with inflammatory pain in multiple small and large joints for 6 months, blackish discolouration of right index finger for 6 months, chest pain and breathlessness for 3 days before presenting to this centre. She was married and had two living children. The dyspnea was sudden in onset, worsened over 3 days, not associated with cough or hemoptysis. Patient also reported alopecia, oral ulcers and Raynaud’s phenomenon. She was not on any treatment and had no significant family history.

On examination, patient was afebrile, distressed, with a pulse rate of 140 beats per minute, regular and low volume; all peripheral pulses were felt. Her blood pressure was 90/60 mmHg, saturation was 95% on room air, with a respiratory rate of 34/min. She had six tender joints and a gangrenous right index finger with line of demarcation up to distal phalanx. Cardiovascular and respiratory systems were normal. On abdominal examination, there was diffuse tenderness in all quadrants, no organomegaly and normal bowel sounds. She had no neurodeficits.

Laboratory investigations showed a mild anaemia of 10.9 g/dL, normal leuckocyte counts and platelets, normal liver, and renal functions. Arterial blood gas showed hypoxia (oxygen 60 mmHg), a carbon dioxide washout of 20 mmHg, normal bicarbonate levels initially. There was sinus tachycardia on electrocardiogram and chest X-ray showed bilateral inhomogeneous opacities. Coronavirus Disease 2019 (COVID-19) Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was negative. Chest Computed Tomography (CT) showed bilateral lower zone inhomogeneous opacities (Table/Fig 1). Pulmonary thromboembolism was ruled out on echocardiography and CT pulmonary angiography.

Her antinuclear antibody by immunofluorescence was 3+ (homogenous), and the blot test revealed presence of SmD1, U1SnRNP, double stranded Deoxyribonucleic Acid (DNA) (ds-DNA) antibodies. The ds-DNA titre was strongly positive (3+) with severe hypocomplementaemia (C3-18.9, C4-9.03). Antiphospholipid antibodies and antineutrophilic cytoplasmic antibody were negative. Urine routine microscopy had 2+ protein, and 24 hours urine had nephrotic range proteinuria of 5.24 gm. Ultrasonography abdomen was normal. Serum amylase and lipase were normal based on these clinical and laboratory features, this patient was diagnosed as Systemic Lupus Erythematosus (SLE).

On day two, 2 g/dL fall in haemoglobin occurred and this indicated a possibility of diffuse alveolar hemorrhage. Thus, a final diagnosis of SLE with musculoskeletal, mucocutaneous features, lupus nephritis with Diffuse Alveolar Haemorrhage (DAH) was made and prompt treatment was started.

She was given oxygen at 4 litres per minute with nasal prongs and empirical ceftriaxone 1 g, 12 hourly, was started intravenously (i.v.). Pulse therapy was started on day 2, with i.v. methyl prednisolone 1 gm for three days, and pulse cyclophosphamide i.v. 750 mg/m2 body surface area, according to the National Institute of Health (NIH) protocol (1). Later, she was continued with oral prednisolone 1 mg/kg/day. The patient underwent five cycles of plasma exchange on alternate days, and improved after each cycle. On day 8, patient hypoxemic respiratory failure worsened, and she was started on non invasive ventilation-pressure support, 100% Fraction of inspired oxygen (FiO2) with Positive End Expiratory Pressure (PEEP) 8 mmHg. On day 10, she developed frank haemoptysis, hypoxemic respiratory failure worsened further, and was intubated with Acute Respiratory Distress Syndrome (ARDS) settings of 100% FiO2, high PEEP and low tidal volume.

Intravenous immunoglobulin therapy and further rituximab was planned, but unfortunately patient succumbed due to continuing alveolar hemorrhage on day 14 of admission, after 6th cycle of plasmapheresis (Table/Fig 2), (Table/Fig 3), (Table/Fig 4).


Systemic lupus erythematosus is a chronic autoimmune disease having clinical features of rashes, arthritis, glomerulonephritis, neurological, cardiovascular involvement, and lung manifestation (2).

Respiratory tract involvement occurs in 50-70% of SLE patients and includes pleuritis, infiltrating pneumonia, bronchiolitis obliterans, pulmonary hypertension, Antiphospholipid Syndrome (APS) and DAH (3). Immune complex induced alveolar capillaritis is the etiology of DAH (4).

The DAH is a severe, rare respiratory complication of SLE, rarer in the early months of the disease. It develops over hours to a few days and is the SLE-associated syndrome with highest mortality. Cardinal clinical features of DAH are a drop in blood haemoglobin, dyspnoea, haemoptysis, diffuse infiltrates on chest imaging, thrombocytopenia and C3 hypocomplementemia. Methylprednisolone and cyclophosphamide are the common drugs used. Rituximab and plasmapheresis are the advanced therapies needed (3),(4).

Dr. William Osler first described DAH in 1904 and it is one of the most devastating complications of SLE. DAH is more common in Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitides and Antiphospholipid Syndrome (5). The DAH is rare, ranging from 0.6% to 5.4% of all SLE patients. Possible etiology is pulmonary capillaritis due to immune complexes which causes damage to basement membranes and leakage of erythrocytes into the alveolar space. The DAH can lead to death in more than 50% cases in the best centres. Acute catastrophic haemoptysis, requirement of mechanical ventilation, infections and thrombocytopenia are causative of mortality (6).

The SLE Disease Activity Index above 10, thrombocytopenia, C3 hypocomplementemia, high anti-dsDNA titres, leukopenia is associated with increased risk of DAH. Risk of DAH is increased with lupus nephritis, described in up to 80% of cases. Acute dyspnoea, hypoxemia, occasionally with haemoptysis, drop in haemoglobin levels (by 1.5-2 g/dL), pulmonary interstitial or alveolar infiltrates could suggest DAH (6).

Methylprednisolone, cyclophosphamide, and plasmapheresis are the most frequently used modalities of treatment. A study found that corticosteroids were the most commonly used (98%) followed by cyclophosphamide (54%), plasmapheresis (31%), intravenous immunoglobulin (IVIG, 5%), mycophenolate (3%), rituximab (RTX, 6%) and stem cell transplantation (2%) (6),(7),(8).

Plasmapheresis is usually used for cases where there is inadequate response to high doses of corticosteroid and cyclophosphamide. In a study on 66 patients with autoimmune diseases subjected to plasmapheresis, 11 were cases of lupus with DAH. Of all patients (total 20) with DAH who were treated, 55% showed improvement (9). Rituximab is a B cell targeted therapy which can be used in DAH but during acute DAH, there may not be sufficient time for the RTX therapy to act (10). Usage of recombinant factor VIIa and extracorporeal membrane oxygenation (ECMO) has been considered in a few cases with uncontrolled bleeding.Newer treatment modalities such as RTX and mesenchymal stem cells (MSCs) should be undertaken in randomised trials (10). Factor VIIa is given at a dose of 35-200 μg/kg, intravenously, either as a single dose or repeated doses every 2-4 hours. it can also be given by intrapulmonary bronchoscopy route with a total dose of 50-90 μg/kg (11),(12).

Many case reports in the literature explain the high mortality of DAH. In 2018, a case report by Abdalla AO et al., of a 23-year-old female with SLE developed multiple episodes of DAH in spite of immunosuppression with steroids, cyclophosphamide and plasmapheresis (13). A study by Martinez MU et al., in 2011, described mortality in 15 of 22 patients with DAH (14). Tolaymat O and Berianu F, reported DAH in 18-year-old male who presented with recurrent episodes of haemoptysis and was diagnosed with SLE,was treated with immunosuppression and plasmapheresis and patient improved gradually (15).

With recent advances, early diagnosis and prompt treatment with immunosuppression and plasmapheresis, survival rates have increased from approximately 25% in the 1980s to 67% in the current decade. Still, DAH is a catastrophic complication which carries high risk of mortality and requires high index of suspicion with prompt early treatment (6).


In critical care settings, DAH needs to be kept in mind in active cases of SLE to institute prompt treatment measures to combat this highly fatal complication.


Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology Guidelines for Screening, Case Definition, Treatment and Management of Lupus Nephritis. Arthritis care & research. 2012;64(6):797. [crossref] [PubMed]
Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. The Lancet. 2014;384(9957):1878-88. [crossref]
Pego-Reigosa JM, Medeiros DA, Isenberg DA. Respiratory manifestations of systemic lupus erythematosus: Old and new concepts. Best practice & research Clinical rheumatology. 2009;23(4):469-80. [crossref] [PubMed]
Al-Adhoubi NK, Bystrom J. Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies. Lupus. 2020;29(4):355-63. [crossref] [PubMed]
Osler W. Landmark Publication from The American Journal of the Medical Sciences: On the Visceral Manifestations of the Erythema Group of Skin Diseases. American Journal of the Medical Sciences. 2009;338(5):396-408. [crossref] [PubMed]
Ednalino C, Yip J, Carsons SE. Systematic review of diffuse alveolar hemorrhage in systemic lupus erythematosus: Focus on outcome and therapy. J Clin Rheumatol. 2015;21(6):305-10. [crossref] [PubMed]
Claridge S, Das P, Dorling A, Robson M. Novel treatment (new drug/intervention; established drug/procedure in new situation): Plasmapheresis as rescue therapy for systemic lupus erthyematosus-associated diffuse alveolar haemorrhage. BMJ Case Reports. 2011;2011. [crossref] [PubMed]
Çetin G, Ozkan T, Turgut S, Karatoprak C, Kazancioglu R. Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus Treated with Double Filtration Plasmapheresis. Bezmialem Science. 2018;6(3). [crossref]
Aguirre-Valencia D, Naranjo-Escobar J, Posso-Osorio I, Macía-Mejía MC, Nieto-Aristizábal I, Barrera T, et al. Therapeutic Plasma Exchange as Management of Complicated Systemic Lupus Erythematosus and Other Autoimmune Diseases. Autoimmune Diseases. 2019;2019. [crossref] [PubMed]
Kazzaz NM, Coit P, Lewis EE, McCune WJ, Sawalha AH, Knight JS. Systemic lupus erythematosus complicated by diffuse alveolar haemorrhage: Risk factors, therapy and survival. Lupus Sci Med. 2015;2(1):e000117. [crossref] [PubMed]
Park JA. Treatment of diffuse alveolar hemorrhage: Controlling inflammation and obtaining rapid and effective hemostasis. Int J Mol Sci. 2021;22(2):01-18. [crossref] [PubMed]
Esper RC, Estrada IEDLM, de la Torre León T, Gutiérrez AOR, López JAN. Treatment of diffuse alveolar hemorrhage secondary to lupus erythematosus with recombinant activated factor VII administered with a jet nebulizer. J Intensive Care. 2014;2(1):47. [crossref] [PubMed]
Abdalla AO, Al-Khafaji J, Akella PM, Taha M. A fatal case of diffuse alveolar hemorrhage as the initial presentation of systemic lupus erythematosus: A case report and literature review. Respiratory Medicine Case Reports. 2018;24:55. [crossref] [PubMed]
Martínez-Martínez MU, Abud-Mendoza C. Predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus. Lupus. 2011;20(6):568-74. [crossref] [PubMed]
Tolaymat O, Berianu F. Systemic Lupus Erythematosus Presenting with Alveolar Hemorrhage. Case Reports in Rheumatology. 2018;2018:01-03. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/55748.16509

Date of Submission: Feb 19, 2022
Date of Peer Review: Mar 21, 2022
Date of Acceptance: Apr 05, 2022
Date of Publishing: Jun 01, 2022

• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

• Plagiarism X-checker: Feb 21, 2022
• Manual Googling: Apr 04, 2022
• iThenticate Software: May 31, 2022 (17%)

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