Systemic Lupus Erythematosus Presenting As Cryptogenic Organizing Pneumonia: Case Report

Anthony Jedd, MD

Sashank Kolli, MD 

Thomas Liao, MD

Isabel Oliva, MD

Loyola University Of Chicago

Stritch School Of Medicine

Maywood, IL

and

University of Arizona

Tucson, AZ

Introduction

Systemic Lupus Erythematosus (SLE) is a systemic disease with multiorgan involvement. In the respiratory system, SLE can involve the lung parenchyma and pleura with intrathoracic manifestations of pleuritis, alveolar hemorrhage and pulmonary fibrosis. Cryptogenic organizing pneumonia (COP) is a rare complication of SLE. We describe a case of newly diagnosed lupus presenting as COP.

Case Report

An 18-year-old woman with no significant past medical history presented to the Emergency Department complaining of generalized malaise, cough and fever for 4 days. Her cough was productive with white to brownish sputum. She complained of chest heaviness/pressure with inability to take deep breaths. Her only reported sick contact was her mother who had the “flu” one week prior to the onset of her illness. She denied any illicit drug use, alcohol or smoking, as well as any recent travel or exotic pet exposure. On admission, her vital signs were: temperature 38.4°C, pulse rate 129 bpm, blood pressure 159/108 mmHg, respiratory rate 29 rpm and oxygen saturation 94% on room air. On physical exam, the patient was in moderate distress with tenderness to palpation over her muscles. Left anterior cervical adenopathy was present and lung auscultation revealed coarse bilateral crackles. She was alert and oriented times 3 with no neurological deficits. 

Laboratory data on admission: white blood cell count 5100/µL with 43% bands, hemoglobin 10.6 g/dL, platelets 125 x 10⁹/L, blood urea nitrogen 37mg/dL, and creatinine 2.0 mg/dL. Urinalysis revealed a large amount of microscopic blood, small amount of leukocyte esterase, moderate bacteria and protein > 300 mg/dl. ABG of pH 7.39/pCO2 28 mm Hg/pO2 of 68 mm Hg on 2L/min by nasal cannula. Initial chest radiograph (CXR) demonstrated bilateral perihilar infiltrates (Figure 1).   

  

Figure 1. CXR on admission.

She was started on ceftriaxone and azithromycin with a working diagnosis of sepsis secondary to community-acquired pneumonia with impending respiratory failure.

She continued to be febrile, hypoxic and tachycardic. A 4-day follow-up CXR demonstrated interval worsening of bilateral airspace disease (Figure 2).

Figure 2. CXR on hospital day 4.

Despite antibiotic therapy for 5 days she was intubated due to continued deterioration. Diagnostic bronchoscopy was performed showing a positive mycoplasma IgM, while samples for bacterial, viral and fungal sources as well blood cultures were negative. GMS stain for Pneumocystis was also negative. At this time infectious disease recommended switching the antibiotics to vancomycin and aztreonam.  

The patient continued to have persistent anemia, thrombocytopenia and urine containing large amounts of protein raising suspicion for an autoimmune hemolytic anemia with bone marrow failure. Rheumatologic panel revealed ANA titer of 2,560 (normal <40), anti-ds DNA antibody >300 IU/ml (normal <10) and normal complement C3,C4. HIV testing was non reactive. Per rheumatology's recommendations, she was started on methylprednisolone 1 g daily for 3 days and later switched to prednisone 100 mg daily and 600 mg cytoxan for the working diagnosis of systemic lupus erythematosus (SLE). After about 1 week of persistent extensive bilateral lung infiltrates and continued ventilator dependence, an open lung biopsy was performed which demonstrated bronchoalveolar tissue showing organizing pneumonia of unknown etiology (Figure 3). No histological findings for vasculitis or alveolar hemorrhage were identified.

 

Figure 3. Panel A: patchy fibroblastic plugs in bronchioles and alveolar ducts (bronchiolitis obliterans) (black arrows). Panel B: Organizing pneumonia within alveoli (black circle).

She was diagnosed with SLE involving multiple organs, which included lung, kidneys and bone marrow. Prednisone 100 mg daily was continued for 2 weeks. Broad spectrum antibiotics were discontinued, but she finished a 2 week coarse of azithromycin for the positive mycoplasma antibodies. Her respiratory status gradually improved and she was extubated on her 14th hospital day. As an outpatient, prednisone was tapered slowly over the next 2 months to 10 mg daily and then she was transitioned to mycophenolate. Follow-up CXR showed resolution of the airspace disease (Figure 4).

Figure 4. CXR 2 months after admission to ICU.

Discussion

Cryptogenic organizing pneumonia is a noninfectious inflammatory pulmonary process that leads to the formation of fibromyxoid connective tissue plugs that adhere to the walls of the alveolar ducts and alveoli (1,2,4). COP can be idiopathic or secondary to several etiologies, including drug toxicity, infection, connective tissue diseases (CTD), malignancy and bone marrow transplantation (6). The diagnosis of SLE-related COP is rare with no cohort studies showing a dominant type of CTD resulting in COP.

Oymak S et al. (8) reviewed etiologic and clinical features in 26 patients with COP and found that 58% were idiopathic. The other 42% were secondary, but the causes were not described. Yoo JW et al. (9) further compared cryptogenic organizing pneumonia and connective tissue disease-related organizing pneumonia (CTD-OP). The study showed rheumatoid arthritis, Sjogren’s syndrome and polymyositis/dermatomyositis were predominant types of CTD and no patients were mentioned with SLE (9). Other studies mention polymyalgia rheumatica and SLE as potential causes of COP, but there are no reported cases of the two entities presenting together in adults (10-12). 

The mechanism by which SLE can lead to the development of COP is unknown. Otsuka et al. (13) suggested that elevated antiphospholipid antibodies contribute to the development of Masson bodies, macrophages and fibrin found within pulmonary alveoli, due to an inhibited inflammatory repair mechanism within the airways, which may contribute to the development of COP. The hypothesis of epithelial damage by the immune system is supported by the response to steroid therapy, which prevents and/or resolves deposition of IgM, IgG and infiltration of plasma cells into the bronchiolar walls (14,15).

The development of SLE-related COP remains a rare entity. Our patient’s presentation was unique in that COP was the initial manifestation of her SLE. Additionally, the pattern of airspace disease on chest radiograph was atypical for organizing pneumonia, which usually presents as either peripheral or peribronchiolar areas of consolidation. As more cases arise, our understanding of the mechanism and timing of the disease will hopefully become more apparent.

References

1. Epler GR, Colby TV, McLoud TC, Carrigton CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985;312:152-8. [CrossRef] [PubMed]
2. Colby TV. Pathologic aspects of bronchiolitis obliterans organizing pneumonia. Chest 1992;102:38S-43S. [CrossRef] [PubMed]
3. Epler GR. Bronchiolitis obliterans organizing pneumonia. Arch Intern Med. 2001;161:158-64. [CrossRef] [PubMed]
4. Moore SL. Bronchiolitis obliterans organzining pneumonia: a late complication of stem cell transplantation. Clin J Oncol Nurs. 2003;7(6):659-62. [CrossRef] [PubMed]
5. Cordier JF. Organizing pneumonia. Thorax 2000;55:318-28. [CrossRef] [PubMed]
6. Roberton B, Hansell D. Organizing pneumonia: a Kaleidoscope of concepts and morphologies. Eur Radiol 2011;21:2244-54. [CrossRef] [PubMed]
7. Takada H, Saito Y, Nomura A, Ohga S, Kuwano K, Nakashima N, Aishima S, Tsuru N, Hara T. Bronchiolitis obliterans organizing pneumonia as an initial manifestation in systemic lupus erythematosus. Pediatr Pulmonol. 2005;40:257-260. [CrossRef] [PubMed]
8. Oymak S, Demirbas HM. Mavili E, Akgun H, Gulmex I, Demir R, Ozesmi M. Bronchiolitis obliterans organizing pneumonia. Respiration. 2005;72:254-62. [CrossRef]  [PubMed]
9. Yoo JW, Song JW, Jang SJ, Lee CK, Kim MY, Lee HK, Jegal Y, Kim DS. Comparison between cryptogenic organizing pneumonia and connective tissue disease-related organizing pneumonia. Rheumatology 2011;50:932-8. [CrossRef] [PubMed]
10. Douglas WW, Tazelaar HD, Hartman TE, Hartman RP, Decker PA, Schroeder DR, Ryu JH. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med. 2001;164(7):1182-5. [CrossRef] [PubMed]
11. Katzenstein ALA, Myers J, Prophet WD, Corley LS 3rd, Shin MS. Bronchiolitis obliterans and usual interstitial pneumonia. Am J Surg Pathol. 1986;10:373-81. [CrossRef] [PubMed]
12. Lynch D. Lung disease related to collagen vascular disease. J Thorac Imaging. 2009;24(4):299-309. [CrossRef] [PubMed]
13. Otsuka F, Amano T, Hashimoto N, Takahashi M, Hayakawa N, Makino H, OtaZ, Ogura T. Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus with antiphopholipid antibody. Intern Med. 1996;35:341-4. [CrossRef] [PubMed]
14. Myers JL, Katzenstein AL. Ultrastructural evidence of alveolar epithelial injury in idiopathic bronchiolitis obliterans-organizing pneumonia. Am J Pathol. 1988;132(1):102-9. [PubMed]
15. Ippolito JA, Palmer L, Spector S, Kane PB, Goveric PD. Bronchiolitis obliterans organizing pneumonia and rheumatoid arthritis. Semin Arthritis Rheum. 1993;23(1):70-8. [CrossRef] [PubMed]

Reference as: Jedd A, Kolli S, Liao T, Oliva I. Systemic lupus erythematosus presenting as cryptogenic organizing pneumonia: case report. Southwest J Pulm Crit Care. 2015;10(2):87-92. doi: http://dx.doi.org/10.13175/swjpcc164-14 PDF 

February 2015 Pulmonary Case of the Month: Severe Asthma

Suresh Uppalapu, MD
Sunil Santhanakrishnan, MD
Rajeev Saggar, MD

Banner Good Samaritan Medical Center

Phoenix, AZ

History of Present Illness

A 50-year-old  African-American woman  with a history of asthma presented to the emergency department with a chief complaint of shortness of breath for 2 weeks. She reported some chest tightness, wheezing  and dry cough. She denied fever, chills, myalgias or arthralgias  at the time of admission.

PMH, SH and FH

In addition to asthma, she has a past medical history of type 2 diabetes mellitus, hypertension, and multiple sclerosis. She admitted to social smoking but states she quit 6 to 7 months ago. She denies alcohol, recreational drug use, or a family history of early coronary artery disease, strokes or cancers. 

Medications

• Montelukast 10 mg daily
• Salmeterol/fluticasone 250/50 inhaled twice a day
• Albuterol inhaler as needed for shortness of breath
• Metformin 500 mg bid.
• Dimethyl fumarate 240 mg bid.
• Omega 3 fish oil.
• Calcium carbonate 600 mg daily
• Naproxen 500 mg BID
• Lisinopril 10 mg daily
• Hydrochlorothiazide 25 mg daily.

Physical Exam

Vitals: Temperature 37.2º C, respiratory rate 33 breaths/min, heart rate 112 beats/min, blood pressure 152/80 mm Hg, SpO2 80% on room air but 98% on 3 liters/min by nasal cannula.

General: Mild respiratory distress.

Lungs: Diminished breath sounds diffusely with mild wheezing.

The rest of her exam was within normal limits.

Laboratory/EKG/Chest Radiography

White blood cells 8.1 X 10³ cells/microliter, hemoglobin 13.9 g/dL, hematocrit 41.7, platelets 289,000 cells/microliter.

Electrolytes blood urea nitrogen, creatinine, glucose, troponin, and brain naturetic peptide were within normal limits

EKG showed sinus tachycardia but was otherwise normal.

Chest x-ray was interpreted as normal.

A thoracic CT scan showed wispy infiltrates but no evidence of pulmonary embolism or other abnormalities.

Which of the following is appropriate management at this time? (Click on the correct answer to proceed to the second of four panels)

1. Bronchodilators
2. Discharge the patient to home
3. Intravenous corticosteroids
4. 1 and 3
5. All of the above

Reference as: Uppalapu S, Santhanakrishnan S, Saggar R. February 2015 pulmonary case of the month: severe asthma. Southwest J Pulm Crit Care. 2015;10(2):57-62. doi: http://dx.doi.org/10.13175/swjpcc010-15 PDF

January 2015 Pulmonary Case of the Month: More Red Wine, Every Time

Uzair Ghori, MD (UGhori@salud.unm.edu)

Shozab Ahmed, MD  (Sahmed@salud.unm.edu)

University of New Mexico

Albuquerque, New Mexico

History of Present Illness

A 41-year-old man travelling from Texas to Las Vegas, Nevada presents to the Emergency Room in Albuquerque, New Mexico with petechial rash, photophobia and headache of 2 weeks duration. The patient complains of general malaise, arthralgia, trouble sleeping, shortness of breath associated with cough and intermittent bilateral lower extremity swelling of 3 weeks duration.

PMH, SH & FH

The patient was prescribed lisinopril and metformin for hypertension and diabetes mellitus, respectively. He admitted occasional drinking, smoking a variable quantity for 30 years but currently not smoking. He denied any illicit drug use.

Physical Exam

Vitals: Heart Rate-92, Blood Pressure-116/45 mm Hg, Respiratory Rate-44 breaths/min, Temperature- 37.2ºC, SpO2-98% on non-rebreather mask.

General: His mental status was not altered.

HEENT: No papilledema was appreciated on eye exam.

Neck: JVP not appreciated.

Lungs: he had diminished breath sounds bilaterally on auscultation.

Heart: His heart had a regular rate and rhythm with no murmurs rubs or gallops.

Abdomen: No abdominal distention or lower extremity edema appreciated.

Skin: A petechial rash was noted most prominently in the lower extremities.

Based on the initial presentation the most appropriate investigations would be? (Click on the correct answer to proceed to the 2nd of 6 panels)

1. CBC, CT head, echocardiogram, blood cultures, metabolic panel, inflammatory markers
2. CBC, UA, lumbar puncture, chest x-ray, inflammatory markers, metabolic panel
3. Echocardiogram, CBC, UA, venous blood gases, bronchoscopy, CT head
4. Stress test, CXR, inflammatory markers, lumbar puncture, ultrasound abdomen, metabolic panel
5. UA, lumbar Puncture, bronchoscopy, echocardiogram, CT head, inflammatory markers 

Reference as: Ghori U, Ahmed S. January 2015 pulmonary case of the month: more red wine, every time. Southwest J Pulm Crit Care. 2015;10(1):1-7. doi: http://dx.doi.org/10.13175/swjpcc155-14 PDF

December 2014 Pulmonary Case of the Month: Bronchiolitis in Adults

Kashif Yaqub, MD

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 61-year-old man was admitted to the hospital with cough, dyspnea and hypoxemia. He had some prior respiratory symptoms about a month prior to admission, but his symptoms worsened recently. He was seen in Family Medicine Clinic on the day of admission and noted to have saturations of 88 – 89%.

A thoracic CT scan was done shortly after his initial symptoms but was negative for lung consolidation or pulmonary embolus. He currently was having fever with temperatures of 99 to 103 degrees and cough that was only slightly productive.

PMH, FH, SH

He had a history of hypertension and obstructive sleep apnea although he was not using continuous positive airway pressure (CPAP).

Medications

• nifedipine
• lisinopril/hydrochlorothiazide
• cough medication

Physical Examination

      General: SpO2 95% on 2l/min by nasal cannula

      Chest: his breath sounds were coarse, but there were no wheezes or crackles.       

      Cardiovascular: regular rate and rhythm with no murmur noted

      Extremities: no clubbing, cyanosis or edema.

      Skin: no rashes noted.

Laboratory

      CBC: Hemoglobin 15.1 d/dL,  WBC 15.3 x 10³ cells/µL, no eosinophilia.

      Procalcitonin: 0.22 ng/mL (normal < 0.15 ng/mL).    

      Nasopharyngeal swab: PCR negative for pertussis, chlamydophila and           mycoplasma pneumonia.

Radiography

His thoracic CT scan at the initial presentation of his illness about a month prior to admission was reviewed (Figure 1).

Figure 1. Representative images from thoracic CT scan in lung windows done about one month prior to admission.

Which of the following are appropriate at this time? (Click on the correct answer to proceed to the next panel)

1. Cocci serology
2. Empirically begin antibiotics for community-acquired pneumonia
3. Repeat the thoracic CT scan
4. Sputum culture
5. All of the above

Reference as: Yaqub K, Wesselius LJ. December 2014 pulmonary case of the month: bronchiolitis in adults. Southwest J Pulm Crit Care. 2014;9(6):297-301. doi: http://dx.doi.org/10.13175/swjpcc149-14 PDF 

November 2014 Pulmonary Case of the Month: BAL Eosinophilia

Salma Imran Patel, MD, MPH

Lewis J. Wesselius, MD

Laszlo T. Vaszar, MD

Departments of Internal Medicine and Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 62 year-old- was admitted to the hospital for 2 weeks of worsening cough, yellowish sputum production, shortness of breath and pleuritic chest pain. The patient has had asthma since the 1970s and presently uses salmeterol/fluticasone and albuterol as a rescue inhaler. He was intubated once four years ago, and has had a total of three hospitalizations for his asthma and 15 courses of prednisone. He is sensitive to cold/hot air, all animals, aspirin and acetaminophen.

PMH, FH, SH

In addition to the asthma, he has a history of type 2 diabetes mellitus, hypertension, gastroesophageal reflux disease, and chronic abdominal pain.

Physical Examination

Vital signs: T 36.6º C, HR 98, BP129/69, RR 20 and SPO2 96% on 2 L of oxygen by nasal cannula. He was mildly distressed and coughing. His pulmonary exam showed diffuse inspiratory and expiratory wheezes. The remainder of his exam was unremarkable.

Laboratory

Significant findings on laboratory evaluation include an elevated white blood cell count of 13,400 cells/ɥL, an elevated absolute eosinophil count of 2,820 eosinophils/ɥL, an elevated glucose of 131 mg/dL, and a low sodium of 120 mEq/L.

Imaging

A thoracic CT scan was performed (Figure 1).

Figure 1. Representative images in lung windows from thoracic CT scan.

Which of the following best describes the CT scan? (click on the correct answer to proceed to the next panel)

1. Cavitary changes in both apices
2. Central consolidation
3. Fibrotic changes at the bases
4. Peripheral opacities
5. Normal

Reference as: Palel SI, Wesselius LJ, Vasczar LT. November 2014 pulmonary case of the month: BAL eosinophilia. Southwest J Pulm Crit Care. 2014;9(5):251-6. doi: http://dx.doi.org/10.13175/swjpcc136-14 PDF