Diffuse alveolar hemorrhage resulting from Pauci-immune pulmonary capillaritis

CASE REPORT

Diffuse alveolar hemorrhage resulting from Pauci-immune pulmonary capillaritis^*

Andreia Salarini Monteiro^I; Gabriela Addor^II; David Henrique Nigri^II; Wilhermo Torres^III; Carlos Alberto de Barros Franco^IV

^IPneumologist. Physician at the Intensive Care Centre Hospital Municipal Miguel Couto

^IIInstructor Physician at the Pneumology Course, Post-Graduation Medical School, PUC/RJ

^IIIHead of the Pathology Division, National Institute for Cancer (INCa). Associate Professor, Pathology Department, Universidade Federal Fluminense

^IVDirector of Barros Franco Clinic. Health Director of the Chest Diseases Institute UFRJ. Pneumology Titular Professor, Post-Graduation Medical School, PUC/RJ. Member of the National Medicine Academy.

^{Correspondence}

ABSTRACT

A 27 year-old female patient, cocaine user, presenting hemoptysis and progressive dyspnea with onset 48 hours prior to hospital admission, without any other signs or symptoms. Serum tests for infectious diseases, collagen disorders and vasculitis were negative. Urinalysis was normal. Computed tomography of the chest showed diffuse alveolar infiltrate, affecting mainly the lower left lobe. A thoracoscopic lung biopsy was performed to clarify the diagnosis. The histopathological findings showed capillaritis and diffuse intra-alveolar hemorrhage. Treated with steroid and cyclophosphamide pulse therapy, a good clinical and radiographical response was obtained. The recently described pauci-immune pulmonary capillaritis is characterized by the presence of isolated pulmonary capillaritis and negative serum testing for auto-immune diseases.

Key words: Hemorrhage. Pulmonary alveolus/pathophysiology

Acronyms and abbreviations used in this paper

ANCA – Antineutrophil cytoplasmic antibodies

BAAR – Alcohol acid resistant bacillus

ANF – Antinuclear factor

RF – Rheumatoid factor

BAL – Bronchial-alveolar lavage

PCR – Polymerase chain reaction

HRCT – High Resolution Computerized Tomography

Introduction

Pulmonary capillaritis leading to diffuse alveolar hemorrhage is usually associated with systemic vasculitis (especially Wegener’s granulomatosis and microscopic poliangitis) but may also be related to collagen vascular diseases (particularly systemic lupus erithematosus), anti-glomerular basement membrane antibody disease and exogenous agents (e.g. isocyanate) or drugs (such as D-penicylamine).⁽¹⁾ Pauci-immune pulmonary capillaritis occurs in the absence of extra-pulmonary clinical manifestations and with negative serum tests for autoimmune diseases.^(2,3)

Case report

A 27 year old advertising woman with no history of previous diseases or smoking habit reported cough and hemoptysis beginning 48 hours prior to hospital admission. Approximately six months before she had presented the same symptoms, with spontaneous remission. In a directed medical history, she reported sporadic use of cocaine moreover coincident with both hemoptysis episodes.

Thorax x-ray showed mixed infiltrate in the lower lobes, primarily the left. The patient was admitted for diagnostic investigation. A chest high resolution computerized tomography (HRCT) showed mixed and diffuse infiltrate, primarily in the lower lobes (Figure 1). Bronchofiberoscopy showed presence of blood along the entire respiratory tract also the bronchial lavage was hemorrhagic. She developed hemoptysis and progressive dyspnea, being admitted to the intensive care unit. She tested negative for collagen diseases (ANF, RF), systemic vasculitis (ANCA, antineutrophil cytoplasmic antibodies) and infectious diseases, including HIV. The anti-phospholipid antibody was negative; complement factor was normal. Sputum smear test, PCR for Mycobacterium tuberculosis and direct fungus test in BAL were negative. Urine test, biochemistry and coagulogram were normal. Blood test disclosed anemia. Echocardiogram was normal. The patient was then submitted to a pulmonary biopsy (medium and lower lobes). Histology and pathology were compatible with small vessels vasculitis (capillaritis) and alveolar hemorrhage (Figure 2).

Treatment with methylprednisolone pulse (1g daily) was begun and after three days cyclophosphamide pulse therapy was added due to severity and persistent worsening of the clinical condition. Plasmapheresis was considered but not carried out in view of clinical improvement. During treatment the patient needed high oxygen flows (under macro-nebulization) but mechanical ventilation was not necessary. Progressive improvement of the symptoms and of the pulmonary infiltrate was noted, leading to discharge after a 17-day hospital stay.

A HRCT (Figure 3) six months after discharge showed complete regression of the pulmonary infiltrate and currently, at a 10-month follow-up, the patient continues asymptomatic.

Discussion

This is the report on a young female patient who presented as first manifestation a diffuse alveolar hemorrhagic syndrome with hemoptysis, cough, anemia, diffuse pulmonary infiltrate and hemorrhagic bronchoalveolar lavage fluid.

Diffuse alveolar hemorrhage is a severe clinical disorder that may be associated (or not) to autoimmune diseases and may be their first manifestation. Although hemoptysis is the most common symptom it is absent in 33% of cases. ^{(3, 4)}

Investigation of patients under suspicion of vasculitis includes medical history, physical examination, clinical laboratory tests, serum tests for autoimmune diseases and also a biopsy, which would be the “gold standard” in diagnosis. There are no reports in literature suggesting higher morbidity or mortality rates when bearers of this condition are submitted to pulmonary biopsy.⁽³⁾ Considering the need for prolonged treatment and its high toxicity it is fundamental to seek a precise diagnosis. In this case, all tests performed were negative, including serum tests for vasculitis or collagen diseases and no extra-pulmonary clinical manifestations (such as sinusitis, hematuria, palpable purpura) were detected, therefore a bronchoscopic pulmonary biopsy was indicated.

Pauci-immune pulmonary capillaritis, which has recently been described, is a small vessel vasculitis only affecting the lung with no clinical or serum indication of associated collagen disease or systemic vasculitis.^(2-4) Histology and pathology show neutrophil infiltrate and alveolar wall edema with fibrinoid necrosis of the capillary walls resulting in leakage of red blood cell, fibrin and neutrophil fragments into the alveolar space.⁽⁵⁾ For this patient, histological and pathological findings were necrotising pulmonary capillaritis and diffuse alveolar hemorrhage without evidence of infectious disease, which associated to negative serum tests confirmed diagnosis.

Metilprednisolone IV pulse with 1g/day for three to five days is the treatment of choice. In more severe cases it may also be associated with cyclophosphamide as IV pulses,.^(3,6) Plasmapheresis has been used in cases resistant to clinical treatment, although its efficacy in diffuse alveolar hemorrhage not related to the Goodpasture syndrome remains controversial.⁽¹⁾ In this case, response to treatment took place a few days after starting immune suppressant therapy. Although cyclophosphamide traditionally has a delayed effect, a possible synergistic action with the corticosteroid justifies its use as pulse therapy. ⁽⁷⁾ Even with a good clinical response, for this condition treatment should be prolonged, with special attention to possible side-effects and also to an eventual relapse.

Reports in literature associating diffuse alveolar hemorrhage with use of cocaine only refer to its acid and thermally stable form (crack). Although hemoptysis may occur in 6 to 26% of crack users, the pathogenesis of diffuse alveolar hemorrhage related to its use remains unclear.^(8-10) There are some recent reports of vasculitis related to the use of 3,4-methilene-dioxy-methanphetamine, known as ecstasy. Since illicit drug users generally consume more than one substance in a short period of time, it may be difficult to identify a single agent responsible for the pathology. ⁽¹⁰⁾ This patient only admitted the use of inhaled cocaine. We must keep in mind that diffuse alveolar hemorrhage related to crack, usually has a rapid, spontaneous solution and that its relationship to histological findings of vasculitis remains undefined, so this diagnosis is unlikely.⁽⁹⁾

In conclusion, for patients with diffuse alveolar hemorrhage and negative serum tests, pulmonary biopsy is indicated due to the possibility of serum negative vasculitis (pauci-immune vasculitis). For the case presented, association of methilprednisolone and cyclophosphamide pulse was apparently beneficial, justifying its use in severely diseased patients.

In similar cases investigation of illicit drug consumption is mandatory.

Acknowledgements

We wish to thank Dr. Marcelo Kalichsztein for carrying out the first bronchoscopy, the Chest Surgery team led by Dr. Paulo de Biasi for carrying out the open pulmonary biopsy, and Drs. Antônio G. Nascimento and Dr. Jeffrey Myers, from Mayo Clinic (Rochester, Minnesota), for reviewing the histology slide of the biopsy.

Received for publication on 11/03/03

Approved, after revision, on 15/05/03

• 1. Lynch JP 3^rd Alveolar hemorrhage syndromes. In: Fishman AP, editor. Fishmans pulmonary diseases and disorders. 3^rd ed. New York: McGraw-Hill, 1998;79:1193-210.
• 2. Jennings CA, King TE Jr, Tuder R, Cherniack RM, Schwarz MI. Diffuse alveolar hemorrhage with underlying isolated, pauciimune pulmonary capillaritis. Am J Respir Crit Care Med 1997;155:1101-9.
• 3. Schwarz MI, Brown KK. Small vessel vasculitis of the lung. Thorax 2000;55:502-10.
• 4. Schwartz MI. Pulmonary vasculitis and hemorrhage. In: Khan M, Almond G, editors. Comprehensive respiratory medicine. Basildon: Mosby, 1999;52:1-9.
• 5. Green RJ, Ruoss SJ, Kraft AS, Duncan SR, Berry GJ, Raffin TA. Pulmonary capillaritis and alveolar hemorrhage Update on diagnosis and management. Chest 1996;110:1305-16.
• 6. Merkel PA, Choi R, Roth MD, Shay AH, Kleerup EC, Simmons MS, et al. Evaluation and treatment of vasculitis in the critically ill patient. Crit Care Clin 2002;18:321-44.
• 7. Lynch JP 3^rd, McCune WJ. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. Am Respir Crit Care 1997;155: 395-420.
• 8. Baldwin GC, Choi R, Roth MD, Shay AH, Kleerup EC, Simmons MS, Tashkin DP. Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal (crack) cocaine. Chest 2002; 121:1231-8.
• 9. Haim DY, Lippmann ML, Goldberg SK, Walkenstein MD. The pulmonary complications of crack cocaine A comprehensive review. Chest 1995;107:233-40.
• 10. Merkel PA. Drug-induced vasculitis. Rheum Dis Clin North Am 2001; 27:849-62.

*

Study performed at Barros Franco Clinic – Advisory for Respiratory Tract Diseases, Rio de Janeiro/RJ. Pneumology Department, Post-Graduation Medical School, PUC/RJ.

Publication Dates

• Publication in this collection
  02 Dec 2003
• Date of issue
  Aug 2003

History

• Received
  11 Mar 2003
• Accepted
  15 May 2003