Correspondence

The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus

N Engl J Med 1999; 341:848September 9, 1999

Article

To the Editor:

Nousari et al. (May 6 issue),1 described acantholytic changes in the respiratory epithelium of two patients with paraneoplastic pemphigus and respiratory failure. They suggested that autoantibodies directed against plakin proteins may be responsible for pulmonary epithelial injury. However, we believe the physiologic mechanism of respiratory failure is not defined. The authors did not specify whether their patients had alveolar hypoventilation, ventilation–perfusion mismatching, right-to-left shunting of blood, or impaired diffusion.

The only relevant functional finding in the two patients was a severe obstruction with hyperinflation. The magnitude of the difference between the alveolar oxygen pressure and the arterial oxygen pressure (derived from Table 1 of the article) and the absence of relevant hypercapnia suggest that intrinsic lung disease was the cause of respiratory failure. Because it is unlikely that the changes described in the bronchial epithelium would have worsened diffusion, mismatching of ventilation and perfusion, shunting, or both could have been the main determinants of respiratory failure in these patients.

Although obstruction of the airways may induce a ventilation–perfusion mismatch, there was no discussion of the contribution to obstruction made by the injury to the large airways described by the authors. The magnitude of the obstruction and the degree of hyperinflation suggest that the role of the small airways was more relevant.2,3 Bronchiolitis obliterans associated with paraneoplastic pemphigus4 could be a more important pathologic cause of respiratory failure than acantholytic changes in the respiratory epithelium.

Francisco García-Río, Ph.D.
Rodolfo Alvarez-Sala, Ph.D.
José M. Pino, Ph.D.
Hospital Universitario La Paz, 28046 Madrid, Spain

4 References

1. 1

   Nousari HC, Deterding R, Wojtczack H, et al. The mechanism of respiratory failure in paraneoplastic pemphigus. N Engl J Med 1999;340:1406-1410
   Full Text | Web of Science | Medline

2. 2

   Wright JL, Cagle P, Churg A, Colby TV, Myers J. Diseases of the small airways. Am Rev Respir Dis 1992;146:240-262
   Web of Science | Medline

3. 3

   Tukiainen P, Taskinen E. Idiopathic bronchiolitis obliterans. In: Epler GR, ed. Diseases of the bronchioles. New York: Raven Press, 1994:181-5.
   

4. 4

   King TE Jr. Bronchiolitis obliterans. Lung 1989;167:69-93
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: García-Río et al. discuss various physiologic mechanisms of pulmonary hypoxemia in patients with paraneoplastic pemphigus and respiratory failure. We did not discuss the mechanisms of hypoxemia in detail. Instead, we focused on the mechanism of respiratory epithelial injury that may have contributed to the progressive obstructive lung disease in our patients and their ultimate deaths from bronchiolitis obliterans. Patient 1 had evidence of bronchiolitis obliterans at the postmortem examination, and we agree that this was the most likely cause of his death. Patient 1 also had tremendous ventilation–perfusion abnormalities on a ventilation–perfusion lung scan, a finding that is common in patients with bronchiolitis obliterans.

The cause of bronchiolitis obliterans is poorly understood, but it may be associated with an insult to the bronchiolar epithelium, which leads to an ineffective repair process and subsequent airway granulation tissue and scarring.1 The finding of respiratory epithelial damage associated with autoantibodies in patients with paraneoplastic pemphigus may provide an important insight into the mechanisms of bronchiolitis obliterans and respiratory failure. Unfortunately, smaller peripheral airways could not be easily studied, and our findings are from the larger airways. Histologic and immunopathological examination of the lesions of the upper airway is critical to the diagnosis of this respiratory complication in patients with paraneoplastic pemphigus. Ciliated respiratory epithelium, however, can extend into the respiratory bronchioles.2 Thus, this respiratory complication could exist in the smaller airways also, resembling bronchiolitis obliterans, but this cannot be substantiated from the current data.

Finally, it should be noted that the early history of Patient 1, before any pulmonary symptoms developed, was previously reported by Lemon et al.3 We should have cited this earlier report and apologize for failing to do so.

Grant J. Anhalt, M.D.
Hossein C. Nousari, M.D.
Johns Hopkins University, Baltimore, MD 21205

Robin Deterding, M.D.
Children's Hospital, Denver, CO 80218

3 References

1. 1

   Lazarus SC. Disorders of the intrathoracic airways. In: Murray JF, Nadel JA, eds. Textbook of respiratory medicine. 2nd ed. Vol. 2. Philadelphia: W.B. Saunders, 1994:1473.
   

2. 2

   Murray JF. The normal lung. Philadelphia: W.B. Saunders, 1976:26.
   

3. 3

   Lemon MA, Weston WL, Huff JC. Childhood paraneoplastic pemphigus associated with Castleman's tumour. Br J Dermatol 1997;136:115-117
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   L. Jing, Z. Shan, H. Yongchu, C. Xixue, Z. Xuejun. (2011) Successful treatment of a paraneoplastic pemphigus in a teenager using plasmapheresis, corticosteroids and tumour resection. Clinical and Experimental Dermatology 36:7, 752-754
   CrossRef

2. 2

   A.B. Cervini, V. Tosi, S.H. Kim, M. Bocian, G. Chantada, C. Nousari, O.G. Carballo, A.M. Pierini. (2010) Pénfigo paraneoplásico/síndrome multiorgánico autoinmune paraneoplásico. Presentación de dos casos en la edad infantil. Revisión de la literatura. Actas Dermo-Sifiliográficas 101:10, 879-886
   CrossRef

3. 3

   Winnie A. Mar, Robin Glaesser, Kristin Struble, Sue Stephens-Groff, Jerry Bangert, Ronald C. Hansen. (2003) Paraneoplastic Pemphigus with Bronchiolitis Obliterans in a Child. Pediatric Dermatology 20:3, 238-242
   CrossRef