Pulmonary Mucormycosis
1977; Elsevier BV; Volume: 72; Issue: 1 Linguagem: Inglês
10.1378/chest.72.1.1
ISSN1931-3543
Autores Tópico(s)Pneumocystis jirovecii pneumonia detection and treatment
ResumoIn the 100 years since pulmonary mucormycosis was first described,1Furbringer P Beobachtungen uber lungenmycose beim Menschen.Virchow's Arch Path Anat. 1876; 66: 330Crossref Scopus (42) Google Scholar only six of approximately 70 reported patients with localized pulmonary involvement have survived.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The most recent successfully treated case, reported in this issue of Chest (see page 92) serves as a timely and encouraging reminder that this, as well as other invasive fungal infections3Pennington JE Successful treatment of Aspergillus pneumonia in hematologic neoplasia.N Engl J Med. 1976; 295: 426Crossref PubMed Scopus (35) Google Scholar need not be fatal. Since mystery and misunderstanding still surround mucormycosis, the answers to the following questions should help clarify the present state of affairs.Who is at risk for infection? Although the specific mechanisms of host resistance to mucormycosis have not been clearly elucidated,4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar experimental and clinical observations have suggested multiple predisposing factors including: acidosis, diabetes, corticosteroid, cytotoxic, and antibiotic therapy, leukopenia, and depressed phagocytosis. The persistence of an uncontrolled underlying disorder, however, is probably the most important single predisposing cause. Thus, over 75 percent of patients with pulmonary mucormycosis have had leukemia or lymphoma.5Meyer RD Armstrong D Mucormycosis: changing status.Crit Rev Clin Lab Sci. 1974; 4: 421Crossref Scopus (104) Google Scholar,6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar The remainder have suffered from diabetes (sometimes very mild), solid tumors, various chronic systemic disorders, and non-neoplastic diseases treated with immunosuppressive agents. Particularly unsettling is the occurrence of at least two fatal cases of pulmonary mucormycosis in healthy individuals.7Bartrum RJ Watnick M Herman PG Roentgenographic findings in pulmonary mucormycosis.Am J Roent Radium Ther Nucl Med. 1973; 117: 810Crossref PubMed Scopus (38) Google Scholar,8Record NB Ginder DR Pulmonary phycomycosis without obvious predisposing factors.JAMA. 1976; 235: 1256Crossref PubMed Scopus (49) Google ScholarWhen should pulmonary mucormycosis be suspected? The typical clinical setting consists of an immunologically compromised patient with “persistent fever and a progressive pulmonary infiltrate” for which no etiologic agent has been demonstrated and which remains unresponsive to antibacterial therapy. Unfortunately, this syndrome is characteristic of infection caused by other opportunistic pathogens (especially Aspergillus). Some patients may be afebrile.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Although not specific for mucormycosis, signs and symptoms of pulmonary infarction are common because the organism has a curious propensity for vascular invasion and thrombosis.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar Indeed, in this clinical setting, pulmonary arteriography has been suggested as a possible diagnostic aid.9Reich J Renzetti AD Pulmonary phycomycosis.Am Rev Respir Dis. 1970; 102: 959PubMed Google Scholar Catastrophic hemoptysis may occur.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Invasive aspergillosis and P aeruginosa infection, however, may also cause pulmonary infarction.10Armstrong D Yound LS Meyer RD et al.Infectious complications of neoplastic disease.Med Clin N Am. 1971; 55: 729Crossref PubMed Scopus (105) Google Scholar Chest roentgenographic patterns are not helpful in suggesting mucormycosis because a variety of nonspecific abnormalities (single or multiple infiltrates, coin lesions, cavities, pleural effusions, fungus balls) may be observed.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar,7Bartrum RJ Watnick M Herman PG Roentgenographic findings in pulmonary mucormycosis.Am J Roent Radium Ther Nucl Med. 1973; 117: 810Crossref PubMed Scopus (38) Google Scholar As with pulmonary aspergillosis,11Murray HW Moore JO Luff RD Disseminated aspergillosis in a renal transplant recipient: diagnostic difficulties re-emphasized.Johns Hopkins Med J. 1975; 137: 235PubMed Google Scholar the chest film may even be normal.12Bodey GP Fungal infections complicating acute leukemia.J Chronic Dis. 1966; 19: 667Abstract Full Text PDF PubMed Scopus (409) Google Scholar Routine laboratory tests provide little diagnostic information, and a positive sputum culture is remarkably rare.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar One might, then, reasonably simplify the answer to this question by stating that when any compromised patient develops a pulmonary lesion, mucormycosis should be suspected.How is the diagnosis made? Recently, it has been appropriately emphasized that negative cultures are the rule with pulmonary mucormycosis.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar This experience has been almost universal even using histologically-positive postmortem specimens.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar Nevertheless, every attempt should be made to culture the organism from blood, sputum, pleural fluid, and biopsy material even though the chance of success is small.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Definitive diagnosis is made by the demonstration of characteristic hyphae in lung tissue which requires one of several readily-available invasive biopsy procedures.13Greenman RL Goodale PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488Abstract Full Text PDF PubMed Scopus (104) Google Scholar There are few patients who are so ill that they cannot tolerate one of these procedures. Although the Mucoraceae may occasionally be cultured from the sputum of normal individuals,4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar a positive culture in high-risk patients is sufficiently unusual and ominous that therapy should be initiated immediately while pursuing more definite evidence of infection. Unfortunately, postmortem examination still remains the principal method of diagnosis.What treatment is available? Because diagnosis during life is exceptional, therapeutic experience is limited. Although in vitro sensitivities are variable, amphotericin B remains the drug of choice. The ability of this drug to penetrate infarcted lung tissue, however, has been questioned.14Medoff G Kobayashi GS Pulmonary mucormycosis.N Engl J Med. 1972; 286: 86Crossref PubMed Scopus (59) Google Scholar 5-fluorocytosine does not appear to be effective.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Surgical intervention, with or without prior administration of amphotericin B, has eradicated and cured localized, nonpulmonary infections,5Meyer RD Armstrong D Mucormycosis: changing status.Crit Rev Clin Lab Sci. 1974; 4: 421Crossref Scopus (104) Google Scholar and it is not surprising that five of the seven survivors of pulmonary mucormycosis underwent lobectomy or segmental resection. Four of the five were diabetics; the fifth had chronic lymphocytic leukemia (CLL) and also received amphotericin B therapy. It is therapeutically encouraging that the other survivors, one with agammaglobulinemia and the other with CLL (see page 92), responded to amphotericin B alone. The decision whether to continue treating the underlying disease with aggressive immunosuppressive-cytotoxic therapy or to withdraw these agents in the face of an invasive fungal infection is difficult and has not been resolved. It would appear likely, however, that if the lesion cannot be surgically resected, cure of pulmonary infection in patients with leukemia and lymphoma is not possible until remission of the disease is achieved and maintained.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google ScholarWhy are there so few survivors? Mucormycosis is uncommon and the diagnosis is not usually seriously considered until late in the disease. The very low yield of routine cultures and the reluctance either to initiate amphotericin B empirically or to subject patients to invasive diagnostic procedures delay diagnosis and therapy, thus allowing infection to progress to an irreversible stage. If multiple, pulmonary lesions are not amenable to resection, any abrupt clinical deterioration may preclude surgery.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Furthermore, many patients with pulmonary mucormycosis also have concomitant life-threatening infections caused by other opportunistic pathogens.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar The inability to control or reverse those factors predisposing to infection, as well as the poor overall clinical status of these patients, contribute importantly to failure of treatment.It is difficult not to be somewhat pessimistic as one considers our present state of knowledge of mucormycosis, and the outlook for those who are unfortunate enough to acquire this unusual infection. Nevertheless, if mucormycosis is suspected early, the diagnosis pursued rapidly and invasively, and the attempts to reverse the conditions predisposing to infection are aggressive, successful treatment of this disorder may no longer be unusual enough to warrant publication. In the 100 years since pulmonary mucormycosis was first described,1Furbringer P Beobachtungen uber lungenmycose beim Menschen.Virchow's Arch Path Anat. 1876; 66: 330Crossref Scopus (42) Google Scholar only six of approximately 70 reported patients with localized pulmonary involvement have survived.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The most recent successfully treated case, reported in this issue of Chest (see page 92) serves as a timely and encouraging reminder that this, as well as other invasive fungal infections3Pennington JE Successful treatment of Aspergillus pneumonia in hematologic neoplasia.N Engl J Med. 1976; 295: 426Crossref PubMed Scopus (35) Google Scholar need not be fatal. Since mystery and misunderstanding still surround mucormycosis, the answers to the following questions should help clarify the present state of affairs. Who is at risk for infection? Although the specific mechanisms of host resistance to mucormycosis have not been clearly elucidated,4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar experimental and clinical observations have suggested multiple predisposing factors including: acidosis, diabetes, corticosteroid, cytotoxic, and antibiotic therapy, leukopenia, and depressed phagocytosis. The persistence of an uncontrolled underlying disorder, however, is probably the most important single predisposing cause. Thus, over 75 percent of patients with pulmonary mucormycosis have had leukemia or lymphoma.5Meyer RD Armstrong D Mucormycosis: changing status.Crit Rev Clin Lab Sci. 1974; 4: 421Crossref Scopus (104) Google Scholar,6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar The remainder have suffered from diabetes (sometimes very mild), solid tumors, various chronic systemic disorders, and non-neoplastic diseases treated with immunosuppressive agents. Particularly unsettling is the occurrence of at least two fatal cases of pulmonary mucormycosis in healthy individuals.7Bartrum RJ Watnick M Herman PG Roentgenographic findings in pulmonary mucormycosis.Am J Roent Radium Ther Nucl Med. 1973; 117: 810Crossref PubMed Scopus (38) Google Scholar,8Record NB Ginder DR Pulmonary phycomycosis without obvious predisposing factors.JAMA. 1976; 235: 1256Crossref PubMed Scopus (49) Google Scholar When should pulmonary mucormycosis be suspected? The typical clinical setting consists of an immunologically compromised patient with “persistent fever and a progressive pulmonary infiltrate” for which no etiologic agent has been demonstrated and which remains unresponsive to antibacterial therapy. Unfortunately, this syndrome is characteristic of infection caused by other opportunistic pathogens (especially Aspergillus). Some patients may be afebrile.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Although not specific for mucormycosis, signs and symptoms of pulmonary infarction are common because the organism has a curious propensity for vascular invasion and thrombosis.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar Indeed, in this clinical setting, pulmonary arteriography has been suggested as a possible diagnostic aid.9Reich J Renzetti AD Pulmonary phycomycosis.Am Rev Respir Dis. 1970; 102: 959PubMed Google Scholar Catastrophic hemoptysis may occur.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Invasive aspergillosis and P aeruginosa infection, however, may also cause pulmonary infarction.10Armstrong D Yound LS Meyer RD et al.Infectious complications of neoplastic disease.Med Clin N Am. 1971; 55: 729Crossref PubMed Scopus (105) Google Scholar Chest roentgenographic patterns are not helpful in suggesting mucormycosis because a variety of nonspecific abnormalities (single or multiple infiltrates, coin lesions, cavities, pleural effusions, fungus balls) may be observed.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar,7Bartrum RJ Watnick M Herman PG Roentgenographic findings in pulmonary mucormycosis.Am J Roent Radium Ther Nucl Med. 1973; 117: 810Crossref PubMed Scopus (38) Google Scholar As with pulmonary aspergillosis,11Murray HW Moore JO Luff RD Disseminated aspergillosis in a renal transplant recipient: diagnostic difficulties re-emphasized.Johns Hopkins Med J. 1975; 137: 235PubMed Google Scholar the chest film may even be normal.12Bodey GP Fungal infections complicating acute leukemia.J Chronic Dis. 1966; 19: 667Abstract Full Text PDF PubMed Scopus (409) Google Scholar Routine laboratory tests provide little diagnostic information, and a positive sputum culture is remarkably rare.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar One might, then, reasonably simplify the answer to this question by stating that when any compromised patient develops a pulmonary lesion, mucormycosis should be suspected. How is the diagnosis made? Recently, it has been appropriately emphasized that negative cultures are the rule with pulmonary mucormycosis.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar This experience has been almost universal even using histologically-positive postmortem specimens.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar Nevertheless, every attempt should be made to culture the organism from blood, sputum, pleural fluid, and biopsy material even though the chance of success is small.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Definitive diagnosis is made by the demonstration of characteristic hyphae in lung tissue which requires one of several readily-available invasive biopsy procedures.13Greenman RL Goodale PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488Abstract Full Text PDF PubMed Scopus (104) Google Scholar There are few patients who are so ill that they cannot tolerate one of these procedures. Although the Mucoraceae may occasionally be cultured from the sputum of normal individuals,4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar a positive culture in high-risk patients is sufficiently unusual and ominous that therapy should be initiated immediately while pursuing more definite evidence of infection. Unfortunately, postmortem examination still remains the principal method of diagnosis. What treatment is available? Because diagnosis during life is exceptional, therapeutic experience is limited. Although in vitro sensitivities are variable, amphotericin B remains the drug of choice. The ability of this drug to penetrate infarcted lung tissue, however, has been questioned.14Medoff G Kobayashi GS Pulmonary mucormycosis.N Engl J Med. 1972; 286: 86Crossref PubMed Scopus (59) Google Scholar 5-fluorocytosine does not appear to be effective.4Williams DM Krick JA Remington JS Pulmonary infections in the compromised host. Part I.Am Rev Respir Dis. 1976; 114: 359PubMed Google Scholar Surgical intervention, with or without prior administration of amphotericin B, has eradicated and cured localized, nonpulmonary infections,5Meyer RD Armstrong D Mucormycosis: changing status.Crit Rev Clin Lab Sci. 1974; 4: 421Crossref Scopus (104) Google Scholar and it is not surprising that five of the seven survivors of pulmonary mucormycosis underwent lobectomy or segmental resection. Four of the five were diabetics; the fifth had chronic lymphocytic leukemia (CLL) and also received amphotericin B therapy. It is therapeutically encouraging that the other survivors, one with agammaglobulinemia and the other with CLL (see page 92), responded to amphotericin B alone. The decision whether to continue treating the underlying disease with aggressive immunosuppressive-cytotoxic therapy or to withdraw these agents in the face of an invasive fungal infection is difficult and has not been resolved. It would appear likely, however, that if the lesion cannot be surgically resected, cure of pulmonary infection in patients with leukemia and lymphoma is not possible until remission of the disease is achieved and maintained.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Why are there so few survivors? Mucormycosis is uncommon and the diagnosis is not usually seriously considered until late in the disease. The very low yield of routine cultures and the reluctance either to initiate amphotericin B empirically or to subject patients to invasive diagnostic procedures delay diagnosis and therapy, thus allowing infection to progress to an irreversible stage. If multiple, pulmonary lesions are not amenable to resection, any abrupt clinical deterioration may preclude surgery.2Murray HW Pulmonary mucormycosis with massive fatal hemoptysis.Chest. 1975; 68: 65Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Furthermore, many patients with pulmonary mucormycosis also have concomitant life-threatening infections caused by other opportunistic pathogens.6Meyer RD Rosen P Armstrong D Phycomycosis complicating leukemia and lymphoma.Ann Int Med. 1972; 77: 871Crossref PubMed Scopus (259) Google Scholar The inability to control or reverse those factors predisposing to infection, as well as the poor overall clinical status of these patients, contribute importantly to failure of treatment. It is difficult not to be somewhat pessimistic as one considers our present state of knowledge of mucormycosis, and the outlook for those who are unfortunate enough to acquire this unusual infection. Nevertheless, if mucormycosis is suspected early, the diagnosis pursued rapidly and invasively, and the attempts to reverse the conditions predisposing to infection are aggressive, successful treatment of this disorder may no longer be unusual enough to warrant publication.
Referência(s)