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Role of surgery in the management of pulmonary sporotrichosis
Role of surgery in the management of pulmonary sporotrichosis Management offour patients with sporotrichosis is summarized: one was treated medically and three were treated surgically. Thirty-seven cases from the literature are reviewed. The role of surgery in the management of pulmonary sporotrichosis is outlined as follows: (I) diagnosis of pulmonary infiltrates and/or pulmonary cavities of undetermined origin, (2) surgical intervention in patients with persistent infiltrates with cavitary lesions resulting from sporotrichosis. following failed medical treatment. and (3) resection of associated pulmonary cavitary lesions in patients in spite of adequte medical control of sporotrichosis. Surgical principles that must be observed in the management of pulmonary sporotrichosis follows: (I) Resection is the procedure of choice. The magnitude ranges from segmental resection to pneumonectomy. Clean resection is necessary. (2) Antifungal drug therapy-preferably with amphotericin B-is advisable preoperatively and postoperatively. since the major cause of late death is progression of the disease when clean resection has not been feasible. (3) Resection combined with drug therapy can be curative without increased risk in physiologically operable and anatomically resectable disease. (4) Thoracoplasty can be a lifesaving procedure for bilateral cavitary lesions with severe hemoptysis in patients with impaired pulmonary functions.
J. Y. Jung, M.D., Carl H. Almond, M.D., Daniel C. Campbell, M.D., Ahmed Elkadi, M.D., and Arturo Tenorio, M.D., Columbia, Mo.
In
the majority of patients with Sporotrichum schenkii infections, skin, subcutaneous tissue, and regional lymph nodes are primarily involved. Pulmonary involvement has been observed in the process of generalized dissemination and manifested as a part of the clinical picture. Primary involvement of the lung is a rare occurrence; however, reports have appeared more frequently in the last decade. This probably reflects an improved diagnostic armamentarium and increased awareness of this disease entity by physicians. We describe our experience with four cases diagnosed and managed of the patients at the Missouri State Chest Hospital. A review of the literature is also presented to summarize the current status of management. Between 1956 and 1977, four diagnoses of primary pulmonary sporotrichosis were made and the patients were treated at the Missouri State Chest Hospital. All were men and their ages ranged from 41 to 59 years.
From the Section of Thoracic and CardiovascularSurgery. University of Missouri Medical Center. Columbia. Mo. Received for publication Feb. 3, 1978. Accepted for publication Oct. 10. 1978. Address for reprints: Carl H. Almond, M.D.• Professor and Chairman. Departmentof Surgery. Universityof South Carolina. 3301 Harden St., Columbia. S. C. 29203.
234
Two of the patients had associated Mycobacterium tuberculosis infection. The other two were free of associated pulmonary disease but one of them had chronic alcoholism. Two patients were treated by surgical resection. A third patient was treated by staged thoracoplasty because of impaired pulmonary function, and the other patient was treated medically. There were no deaths. A brief presentation of the four cases follows.
Case reports CASE 1. A 59-year-old white man was admitted to the Missouri State Chest Hospital in March, 1956, because of a productive cough. fever. general malaise. chest pain. and intermittent hemoptysis of 3 months' duration. Physical examination revealed diminished breath sounds and increased resonance over the left hemithorax. Several sputum cultures revealed M. tuberculosis. Chest roentgenogram revealed advanced cavitary disease in the left apex. Mycologic studies. including sputum smears and cultures. skin tests. and complement fixation tests were all negative. Antituberculosis therapy with INH and para-aminosalicylic acid (PAS) was initiated. Conversion of the sputum for acid-fast bacilli (AFB) was obtained in November. 1956. The patient was discharged with the advice to continue using medications but he was uncooperative and refused to do so. In March. 1958. he was readmitted with similar complaints. Sputum cultures were positive for M. tuberculosis. In addition. S. schenkii was repeatedly isolated from sputum and amphotericin B therapy was recommended. The patient left the hospital against medi-
0022-5223/79/020234+06$00.60/0 © 1979 The C. V. Mosby Co.
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Fig. I. Chest x-ray film of our Case 4. Right upper lobe infiltrate s and cavity are evident. A. Posteroanterior view. B. Lateral view . cal advice and subsequently returned to the hospital in September, 1959, with marked weakne ss and debilitation. Sputum was negative for AFB, but a positive culture of S. schenkii was obtained. Forty-three positive cultures were obtained from him between 1959 and 1961. He received amphotericin B treatment at a total dose of 3,100 mg . in a 3 month period, followed by a saturated solution of potassium iodide for 5 months . Chest x-ray films persistently revealed advanced cavitary lesions in the left upper lobe. During medical treatment, he had an episode of massive hemoptysis . Pulmonary function tests showed marked restrictive deficiency , which contraindicated resection . Staged thoracoplasty was carried out with successful obliteration of cavities . The patient's general status was markedly improved despite positive sputum cultures of S. schenkii . The patient was last seen in April , 1961, and was lost to further follow-up. CAS E 2. A 41-year-old white man was admitted in February, 1962, with a 2 year history of intermittent hemoptysis, cough , general malaise , fever, and weight loss. He had been hospitalized elsewhere and treated for pulmonary tuberculosis . He was treated with lNH and PAS for a year. He also underwent a left upper lobectomy and a superior segmentectomy of the left lower lobe . Postoperatively, he continued to be symptomatic despite continuous medication with INH, PAS, and streptomycin. On admission to Missouri State Chest Hospital, the chest x-ray film revealed a contracted left hemithorax, thickened pleura in the left upper pleural cavity, and a cavitary lesion in the remaining left lung. Sputum cultures revealed both M. tuberculosis and S. schenkii . Severe left endobronchial disease was disclosed on bronchoscopic
examination. Antituberculosis and amphotericin B therapy was initiated . He received 2,475 mg. of amphotericin B over a period of 16 weeks . Endobronchial disease was markedly improved, but the bronchogram revealed marked bronchiectasis. Sputum cultures showed no growth of S. schenkii but were persistently positive for AFB . Therefore, a complete pneumonectomy was carried out by the extrapleural approach. His general status then markedly improved. Subsequent sputum cultures were negative for both S. schenkii and AFB . CAS E 3 . A 51-year-old white man was admitted to the Missouri State Chest Hospital in January, 1971, because of left-sided chest pain, cough , and dyspnea. Chest roentgenogram revealed a small cavitary lesion with a surrounding infiltrate in the left upper lobe . Sputum was negative for AFB but positive for S. schenkii on four occasions. Results of complement fixation and skin tests were negative. Amphotericin B treatment was initiated with 2,355 mg . administered in a period of 16 weeks . Repeat chest x-ray films showed disappearance of the cavity in the left upper lobe . The infiltrate cleared in the subsequent 6 months' follow-up. Sputum and cultures were negative. CAS E 4 . A 42-year-old white man was referred to the Missouri State Chest Hospital because of abnormal chest x-ray films; he had been treated at another state hospital for alcoholism. The chest roentgenogram was obtained during a routine examination and revealed an infiltrate along with a cavitary lesion (Fig . I, A and B) . He denied cough , shortness of breath, or history of hemoptysis. Sputum cytology, smear, and culture were negative for AFB. Sputum cultures were
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•
Fig. 2. Smear from the necrotic tissue in the right upper lobe cavity. Spherical budding shells and cigar-shaped bodies suggestive of S. schenkii are demonstrated. (GMS stain). positive on five consecutive occasions for S. schenkii. A specimen from selective brushings also yielded a positive culture for S. schenkii. Both latex and tube agglutination tests were positive for S. schenkii. A short course of amphotericin B (550 mg.) therapy was followed by a right upper lobectomy because of almost complete destruction of the right upper lobe. Smear of the necrotic tissue in the cavity demonstrated spherical. budding shells and cigar-shaped bodies suggestive of S. schenkii (Fig. 2). He has had a rather uneventful postoperative course except for a prolonged air leak. S. schenkii was cultured from the surgical specimen. The follow-up sputum cultures were negative.
Discussion Sporotrichum schenkii was first recognized in 1898 by Shenk as a fungus that caused cutaneous lesions. Since then, S. schenkii infections have been observed in and reported from various parts of the world. This organism usually affects the skin, probably being implanted in the skin by trauma, and produces polymorphous lesions. It varies from simple ulcer to circumscribed, painless subcutaneous nodules along with localized lymphadenitis or lymphangitis. Generalized dissemination with multisystem involvement is uncommon, but it may involve mucous membranes, muscles, bone and joints, eyes, meninges, and other viscera, probably through hematogenous spread. The
lung may be involved in the dissemination process or as a primary and sole site of infection. In either case, lung involvement is rare. It is known that the fungus is a saphrophyte in nature and ubiquitous in distribution. It has been isolated from soil, humus bank, timbers, sphagnum moss, and various wild and cultivated plants. Spore size ranges from 2 to 31J-, so the possibility of primary pulmonary infection after inhalation of spores should be entertained. Recently, Michelson! pointed out the possibility of another mode of infection through bronchial aspiration since six of the 15 patients with pulmonary sporotrichosis reviewed by him had chronic alcoholism. Of our four patients, two were heavy alcohol users. The significance of this association needs to be elucidated. Primary pulmonary sporotrichosis is rare. To our knowledge, only 37 cases have been reported in the literature. We have added our four cases for a total of 41. These 41 cases form the basis for the analysis and discussion in the following paragraphs. Some cases reported in the early part of the century lack either some pertinent laboratory confirmation or else treatment or follow-up information. For the purpose of completeness in the review of the literature, these cases are included. Previously it was assumed that sporotrichosis most often affected the farmer and garden attendant; however, the disease may also affect urban residents. Symptoms are not specific: they range from mild febrile illnesses to hemoptysis, general malaise, weight loss, and respiratory failure. Roentgenographically, it is very difficult to differentiate from tumor and other granulomatous diseases, especially tuberculosis. In fact, these diseases may co-exist with sporotrichosis. Many patients were initially suspected of having M. tuberculosis infection after viewing roentgenographs. In spite of repeated negative sputum cultures and smears, antituberculous drugs have been administered either until no response was demonstrated or until the diagnosis of sporotrichosis was confirmed. Roentgenographic findings vary from streaks of infiltrate to multiple thinwalled cavity formations. The disease seems to preponderantly involve upper lobes, but other parts of the lung field may also be affected. Typically, it appears as unilateral or bilateral apical infiltrates progressing to cavitation. Exceptions are those cases in which the lung lesion is a part of the dissemination process. In this circumstance, the lung lesion may appear as a solitary nodule or multiple small nodules without accompanying infiltrates or cavitary formation. Fungus ball in the cavity is a rare finding having been reported only once in 37 cases. Diagnosis is made or confirmed primarily by (I) re-
Volume 77 Number 2 February, 1979
peated sputum cultures, (2) positive cultures from bronchial washings or selective brushings, (3) positive cultures from lung tissue obtained from the surgical specimen or discovered on cytologic observation, and (4) positive complement fixation or agglutination tests. Results of the serologic tests are not documented or obtained uniformly in all reported cases. These tests may have great diagnostic value, but information about their specificity and relation to the severity of the disease process is insufficient. Medical treatment of patients with S. schenkii has not been standardized. Since the classic report of DeBeurmann and Gougerot," potassium iodide therapy has been employed continuously in the treatment of all forms of S. schenkii infection. A long list of successful treatments in cases of cutaneous lymphatic sporotrichosis has been documented and the effectiveness of such treatment demonstrated, despite the fact that potassium iodide does not act directly against S. schenkii. According to in vitro studies, S. schenkii could grow in media containing 10 percent potassium iodide." Experimental data of Davis" also demonstrated that potassium iodide has no direct effect on S. schenkii, but does induce marked connective tissue reaction around the necrotic area caused by this organism. Potassium iodide was administered to 25 patients with pulmonary sporotrichosis in this collective series from the literature. In II patients this drug was used alone. The result is unknown in one case, and in spite of treatment in two patients progressive disease caused death. The rest of the patients showed improvement or cure. In the other 15 cases, iodide therapy was a part of the combined drug regimen or constituted preoperative and/or postoperative coverage. Since more effective antifungal drugs are available, efficacy of potassium iodide treatment for pulmonary sporotrichosis is difficult to evaluate at present, but it seems that only those mild cases involving pulmonary infiltrates without cavity formation responded to iodide therapy. Other antifungal drugs have been introduced and tried clinically. Because of the rarity and severity of this disease, double-bind studies could not be carried out and comparative effects of these drugs could not be determined. Griseofulvin has been employed successfully in control of the cutaneous form of sporotrichosis."- 6 One patient responded well to treatment with griseofulvin in combination with iodide. Closure of a 4 em. cavity and clearing of infiltrates were observed. Experimental therapy with griseofulvin showed no effect on the lethal outcome or the culture result of S. schenkii infection in mice." Hydroxystilbamidine has been tried but the result is hard to evaluate.
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Amphotericin B is the drug used most frequently in recent cases. Sufficient experience has been accumulated to confirm its effectiveness against a variety of fungi. Its use in controlling pulmonary sporotrichosis was shown in one reported case and in our Case 3. The linear infiltrates responded well (they disappeared) and complete cure was attained by means of amphotericin B treatment alone. In another instance, the patient had thick-walled cavities in both apices of the lung as well as a perirectal abscess caused by sporotrichosis. He received amphotericin B, which did not arrest the disease process, and eventually died. Another patient with infiltrate and a cavitary lesion improved clinically on amphotericin B treatment; however, a fungus ball developed within the cavity and culture was positive for Aspergillus. Surgical resection was refused and the final outcome was not recorded. More recently, miconazole has been tried in a patient who failed to improve on amphotericin Band flucytosine treatment. 8 Initial improvement, as evidenced by negative sputum cultures and lowering of serum agglutinin titer, was observed. Further trials are needed to assess the clinical efficacy of this drug. In the other cases, surgical intervention was necessary. Amphotericin B or other antifungal drugs were used for initial treatment and postoperative coverage. At present, it is fair to say antifungal drug therapy has achieved success in some cases but is not uniformly satisfactory. The major problem is that comparative data are lacking for setting any minimal or optimal dose of drugs to be administered for the duration of drug therapy. Surgical intervention was necessary in three patients in the reported series because the true nature of the underlying lung disease could not be ascertained. S. schenkii was isolated from the surgical specimen in one of these cases. Tissue section and smear in one of these were very suggestive of S. schenkii. Consequently, iodide therapy was initiated in both instances. In one of these the surgical specimen failed to reveal any specific diagnosis. Sporotrichosis was not uncovered until progression of the disease involving the remaining left lower lobe yielded positive sputum culture. Fifteen patients from the reported series required 17 operations. Lobectomies were carried out most frequently-seven were left upper lobectomies and three were right upper lobectomies. Pneumonectomy was necessary in two patients. Segmental resections were performed in three and combined lobectomy and segmentectomy was necessary in one. In one patient thoracotomy and biopsy were done. This was later followed by a bisegmental resection because the diagnosis had been established and the condition had progressed to
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cavitary disease in spite of medical treatment. In one patient a left upper lobectomy was performed for undiagnosed infiltrates and cavitary lesion. The disease progressed to involve the left lower lobe after the operation, and sputum cultures were positive for S. schenkii. Completion pneumonectomy was necessary. However, the patient died of progressive disease that invaded the right lung, despite treatment with multiple combined antifungal drugs. The other patients who underwent pneumonectomy also died, but as a result of the development of bronchopleural fistula and Pseudomonas infection. The other death occurred after a left upper lobectomy because of extension of the disease process to the right upper lobe, despite therapy with various combinations of drugs (amphotericin B, hydroxystilbamidine, and iodide). Thus operative deaths occurred in three; however, only one was related directly to the surgical procedure. The other two deaths were due to the inability to arrest the disease despite drug therapy and surgical resections. In another reported case, initial closure of the right apical cavitary lesion after amphotericin B therapy was noted, but a left upper lobectomy was performed because of persistent cavitary lesion. Recurrence of the disease with M. tuberculosis infection involving the left midlung field was confirmed 22 months after resection. Combined antituberculosis and amphotericin B therapy was started and the result was not mentioned. The rest of the patients had uneventful recoveries. It should be emphasized that all patients were covered by one or more drugs in the preoperative or postoperative period. From these data, we may state that surgical intervention was carried out for diagnostic or therapeutic purposes in persistent infiltrates and cavitary lesions, after medical treatment. Death was directly related to surgical intervention in one patient. Late death in two patients was attributable to progression of disease combined medical treatment and surgical resection. Recurrence of disease was observed in another patient who also underwent resection, but the outcome was not recorded. Our surgical experience is with three patients, two of whom underwent surgical resection with uneventful recoveries. The other patient's condition was complicated by concomitant pulmonary tuberculosis and left apical cavities. He was not considered to be a candidate for resection because of severe pulmonary functional impairment. Thoracoplasty was done in stages as a lifesaving procedure to ameliorate repeated massive hemoptysis. The cavities were successfully collapsed. The patient showed marked improvement and was discharged in spite of positive sputum cultures for S.
Thoracic and Cardiovascular Surgery
schenkii. Unfortunately, he was very uncooperative since he had a chronic drinking problem, and was lost to follow-up. The final outcome is unknown. The patient with small cavities and infiltrates was successfully managed with amphotericin B, as evidenced by clearing of the infiltrate and closing of the cavities. Summary
I. Pulmonary sporotrichosis is a severe pulmonary infection. Medical treatment is successful in mild cases involving pulmonary infiltrates alone or small cavities. 2. With medical treatment alone, fatal outcome was observed in six cases. Various antifungal drugs have been tried, but adequate dosage and duration of the therapy have not been standardized. The result of therapy was not uniformly satisfactory. 3. Surgical intervention is indicated: with undiagnosed pulmonary infiltrates or pulmonary cavities; in persistent infiltrates with cavitary lesions after medical treatment in suitable candidates; and in the treatment of associated pulmonary lesions such as cavitary pulmonary tuberculosis. Surgical principles to be observed in the management of pulmonary sporotrichosis follow: I. Resection is the procedure of choice. The magnitude of resection ranges from segmental resection to pneumonectomy, depending on the extent of the disease. Clean resection is necessary. 2. Antifungal drug therapy-preferably with amphotericin B-is advisable preoperatively and postoperatively, since the major cause of late death is progression of the disease when clean resection has not been feasible. 3. Surgical resection combined with drug therapy can be curative, in physiologically operable and anatomically resectable disease without increased risks. REFERENCES
2
3 4 5
6
Michelson E: Primary pulmonary sporotrichosis. Ann Thorac Surg 24: 83, 1977 DeBeurmann L, Gougerot H: Associations morbides dans les sporotrichosis heme observation de sporotrichose. Bull Soc Med Paris 24: 591, 1907 Emmons CW, Binford CH, Utz JP: Medical mycology, ed 2, London, 1963, Henry Kimpton, p 368 Davis OJ: The effect of potassium iodide on experimental sporotrichosis. J Intern Dis 25: 124, 1919 Gonzalez OAG: Griseofulvin in Systemic Mycosis, Conference on Medical Mycology, New York Academy Science, 1960 LaTapi F, LaValle P, Novles J, Ortiz Y: Griseofulvin en micosis cutaneas profundes. Dermatologia (Mexico) 3: 34, 1959
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7 Tsubura E, Schwartz J: Treatment of experimental sporotrichosis in mice with griseofulvin and amphotericin-B. Antibiot Chemother 10: 753, 1960 8 Rohwedder JJ, Archer G: Pulmonary sporotrichosis. Treatment with miconazole. Am Rev Respir Dis 114: 403, 1976 ADDITIONAL REFERENCES Baum GL, Donnerberg RL, Stewart 0, Mulligan WJ, Putman LR: Pulmonary sporotrichosis. N Engl J Med 280: 410, 1969 Beland JE, Mankiewicz E, MacIntosh OJ: Primary pulmonary sporotrichosis. Can Med Assoc J 99: 813, 1968 Chantemesse and Rodriques: Quoted in DeBeurman L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Comstock C, Wolson A: Roentenology of sporotrichosis. Am J Roentgenol 125: 651, 1974 Cruthirds TP, Patterson DO: Primary pulmonary sporotrichosis. Am Rev Respir Dis 95: 845, 1967 DeBeurmann L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Deleixhe E: Un cas de sporotrichose pulmonaire. Rev Med Liege 11: 444, 1956 D'Hanoi S: Quoted in DeBeurmann L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Dominguez: Quoted in Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Edgahl A: Chronic non-tuberculous disease of the lung with a report of a case of fungous infection of the right lung, probably the Sporotrichum schenckii. III Med J 61: 422, 1932 Evers RH, Whereatt RR: Pulmonary sporotrichosis. Chest 66: 91,1974 Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Formicola P: Pulmonary sporotrichosis in man, a case. Morgagni 74: 1591, 1932 Khan FA, Guarneri JJ, Sierra MF: Primary pulmonary sporotrichosis complicated by perirectal abscess. Am Rev Respir Dis 112: 119, 1975
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Kinas HY, Smulewicz JJ: Primary pulmonary sporotrichosis. Respiration 33: 468, 1976 Kluge RM, Hornick RB: Sporotrichosis. An unusual disseminated cutaneous case and a fatal pulmonary case. South Med J 69: 855, 1976 Liu CL: Sporotrichosis. Report of a case. Chin M J 73: 330, 1955 McGavran MH, Kobayashi G, Newmark L, Newberry M, Miller CA, Harford CG: Pulmonary sporotrichosis. Dis Chest 56: 547, 1969 Mohr JA, Patterson CD, Eaton BG, Rhoades ER, Nichols NB: Primary pulmonary sporotrichosis. Am Rev Respir Dis 106: 260, 1972 Nicaud: Quoted in Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Post GW, Jackson A, Garber PE, Veach GE: Pulmonary sporotrichosis. Dis Chest 34: 455, 1958 Ridgeway NA, Whitcomb FC, Erickson EE, Law SW: Primary pulmonary sporotrichosis. Report of two cases. Am J Med 32: 153, 1962 Scott SM, Peasley ED, Crymes TP: Pulmonary sporotrichosis. Report of two cases with cavitation. N Engl J Med 265: 453, 1961 Serstock OS, Zinneman HH: Pulmonary and articular sporotrichosis. Report of two cases. JAMA 233: 1291, 1975 Siegrist HD, Ferrington E: Primary pulmonary sporotrichosis. South Med J 53: 728, 1965 Singer JJ: Pulmonary sporotrichosis, report of two cases. Am Rev Tuberc 18: 438, 1928 Smith AG, Morgan WKC, Hornick RB, Funk AM: Chronic pulmonary sporotrichosis. Report of a case, including morphologic and mycologic studies. Am J Clin Pathol 54: 401, 1970 Smith DT: The Chest, Myers, McKinlay, eds., Springfield, Ill., 1949, Charles C Thomas, Publisher Trevathan RD, Phillips S: Primary pulmonary sporotrichosis. JAMA 195: 965, 1966 Voss JA: Case of sporotrichosis of lungs. Nor Mag F Laegevidensk 96: 14, 1935
J. Y. Jung, M.D., Carl H. Almond, M.D., Daniel C. Campbell, M.D., Ahmed Elkadi, M.D., and Arturo Tenorio, M.D., Columbia, Mo.
In
the majority of patients with Sporotrichum schenkii infections, skin, subcutaneous tissue, and regional lymph nodes are primarily involved. Pulmonary involvement has been observed in the process of generalized dissemination and manifested as a part of the clinical picture. Primary involvement of the lung is a rare occurrence; however, reports have appeared more frequently in the last decade. This probably reflects an improved diagnostic armamentarium and increased awareness of this disease entity by physicians. We describe our experience with four cases diagnosed and managed of the patients at the Missouri State Chest Hospital. A review of the literature is also presented to summarize the current status of management. Between 1956 and 1977, four diagnoses of primary pulmonary sporotrichosis were made and the patients were treated at the Missouri State Chest Hospital. All were men and their ages ranged from 41 to 59 years.
From the Section of Thoracic and CardiovascularSurgery. University of Missouri Medical Center. Columbia. Mo. Received for publication Feb. 3, 1978. Accepted for publication Oct. 10. 1978. Address for reprints: Carl H. Almond, M.D.• Professor and Chairman. Departmentof Surgery. Universityof South Carolina. 3301 Harden St., Columbia. S. C. 29203.
234
Two of the patients had associated Mycobacterium tuberculosis infection. The other two were free of associated pulmonary disease but one of them had chronic alcoholism. Two patients were treated by surgical resection. A third patient was treated by staged thoracoplasty because of impaired pulmonary function, and the other patient was treated medically. There were no deaths. A brief presentation of the four cases follows.
Case reports CASE 1. A 59-year-old white man was admitted to the Missouri State Chest Hospital in March, 1956, because of a productive cough. fever. general malaise. chest pain. and intermittent hemoptysis of 3 months' duration. Physical examination revealed diminished breath sounds and increased resonance over the left hemithorax. Several sputum cultures revealed M. tuberculosis. Chest roentgenogram revealed advanced cavitary disease in the left apex. Mycologic studies. including sputum smears and cultures. skin tests. and complement fixation tests were all negative. Antituberculosis therapy with INH and para-aminosalicylic acid (PAS) was initiated. Conversion of the sputum for acid-fast bacilli (AFB) was obtained in November. 1956. The patient was discharged with the advice to continue using medications but he was uncooperative and refused to do so. In March. 1958. he was readmitted with similar complaints. Sputum cultures were positive for M. tuberculosis. In addition. S. schenkii was repeatedly isolated from sputum and amphotericin B therapy was recommended. The patient left the hospital against medi-
0022-5223/79/020234+06$00.60/0 © 1979 The C. V. Mosby Co.
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Number 2 February. 1979
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Fig. I. Chest x-ray film of our Case 4. Right upper lobe infiltrate s and cavity are evident. A. Posteroanterior view. B. Lateral view . cal advice and subsequently returned to the hospital in September, 1959, with marked weakne ss and debilitation. Sputum was negative for AFB, but a positive culture of S. schenkii was obtained. Forty-three positive cultures were obtained from him between 1959 and 1961. He received amphotericin B treatment at a total dose of 3,100 mg . in a 3 month period, followed by a saturated solution of potassium iodide for 5 months . Chest x-ray films persistently revealed advanced cavitary lesions in the left upper lobe. During medical treatment, he had an episode of massive hemoptysis . Pulmonary function tests showed marked restrictive deficiency , which contraindicated resection . Staged thoracoplasty was carried out with successful obliteration of cavities . The patient's general status was markedly improved despite positive sputum cultures of S. schenkii . The patient was last seen in April , 1961, and was lost to further follow-up. CAS E 2. A 41-year-old white man was admitted in February, 1962, with a 2 year history of intermittent hemoptysis, cough , general malaise , fever, and weight loss. He had been hospitalized elsewhere and treated for pulmonary tuberculosis . He was treated with lNH and PAS for a year. He also underwent a left upper lobectomy and a superior segmentectomy of the left lower lobe . Postoperatively, he continued to be symptomatic despite continuous medication with INH, PAS, and streptomycin. On admission to Missouri State Chest Hospital, the chest x-ray film revealed a contracted left hemithorax, thickened pleura in the left upper pleural cavity, and a cavitary lesion in the remaining left lung. Sputum cultures revealed both M. tuberculosis and S. schenkii . Severe left endobronchial disease was disclosed on bronchoscopic
examination. Antituberculosis and amphotericin B therapy was initiated . He received 2,475 mg. of amphotericin B over a period of 16 weeks . Endobronchial disease was markedly improved, but the bronchogram revealed marked bronchiectasis. Sputum cultures showed no growth of S. schenkii but were persistently positive for AFB . Therefore, a complete pneumonectomy was carried out by the extrapleural approach. His general status then markedly improved. Subsequent sputum cultures were negative for both S. schenkii and AFB . CAS E 3 . A 51-year-old white man was admitted to the Missouri State Chest Hospital in January, 1971, because of left-sided chest pain, cough , and dyspnea. Chest roentgenogram revealed a small cavitary lesion with a surrounding infiltrate in the left upper lobe . Sputum was negative for AFB but positive for S. schenkii on four occasions. Results of complement fixation and skin tests were negative. Amphotericin B treatment was initiated with 2,355 mg . administered in a period of 16 weeks . Repeat chest x-ray films showed disappearance of the cavity in the left upper lobe . The infiltrate cleared in the subsequent 6 months' follow-up. Sputum and cultures were negative. CAS E 4 . A 42-year-old white man was referred to the Missouri State Chest Hospital because of abnormal chest x-ray films; he had been treated at another state hospital for alcoholism. The chest roentgenogram was obtained during a routine examination and revealed an infiltrate along with a cavitary lesion (Fig . I, A and B) . He denied cough , shortness of breath, or history of hemoptysis. Sputum cytology, smear, and culture were negative for AFB. Sputum cultures were
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Thoracic and Cardiovascular Surgery
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Fig. 2. Smear from the necrotic tissue in the right upper lobe cavity. Spherical budding shells and cigar-shaped bodies suggestive of S. schenkii are demonstrated. (GMS stain). positive on five consecutive occasions for S. schenkii. A specimen from selective brushings also yielded a positive culture for S. schenkii. Both latex and tube agglutination tests were positive for S. schenkii. A short course of amphotericin B (550 mg.) therapy was followed by a right upper lobectomy because of almost complete destruction of the right upper lobe. Smear of the necrotic tissue in the cavity demonstrated spherical. budding shells and cigar-shaped bodies suggestive of S. schenkii (Fig. 2). He has had a rather uneventful postoperative course except for a prolonged air leak. S. schenkii was cultured from the surgical specimen. The follow-up sputum cultures were negative.
Discussion Sporotrichum schenkii was first recognized in 1898 by Shenk as a fungus that caused cutaneous lesions. Since then, S. schenkii infections have been observed in and reported from various parts of the world. This organism usually affects the skin, probably being implanted in the skin by trauma, and produces polymorphous lesions. It varies from simple ulcer to circumscribed, painless subcutaneous nodules along with localized lymphadenitis or lymphangitis. Generalized dissemination with multisystem involvement is uncommon, but it may involve mucous membranes, muscles, bone and joints, eyes, meninges, and other viscera, probably through hematogenous spread. The
lung may be involved in the dissemination process or as a primary and sole site of infection. In either case, lung involvement is rare. It is known that the fungus is a saphrophyte in nature and ubiquitous in distribution. It has been isolated from soil, humus bank, timbers, sphagnum moss, and various wild and cultivated plants. Spore size ranges from 2 to 31J-, so the possibility of primary pulmonary infection after inhalation of spores should be entertained. Recently, Michelson! pointed out the possibility of another mode of infection through bronchial aspiration since six of the 15 patients with pulmonary sporotrichosis reviewed by him had chronic alcoholism. Of our four patients, two were heavy alcohol users. The significance of this association needs to be elucidated. Primary pulmonary sporotrichosis is rare. To our knowledge, only 37 cases have been reported in the literature. We have added our four cases for a total of 41. These 41 cases form the basis for the analysis and discussion in the following paragraphs. Some cases reported in the early part of the century lack either some pertinent laboratory confirmation or else treatment or follow-up information. For the purpose of completeness in the review of the literature, these cases are included. Previously it was assumed that sporotrichosis most often affected the farmer and garden attendant; however, the disease may also affect urban residents. Symptoms are not specific: they range from mild febrile illnesses to hemoptysis, general malaise, weight loss, and respiratory failure. Roentgenographically, it is very difficult to differentiate from tumor and other granulomatous diseases, especially tuberculosis. In fact, these diseases may co-exist with sporotrichosis. Many patients were initially suspected of having M. tuberculosis infection after viewing roentgenographs. In spite of repeated negative sputum cultures and smears, antituberculous drugs have been administered either until no response was demonstrated or until the diagnosis of sporotrichosis was confirmed. Roentgenographic findings vary from streaks of infiltrate to multiple thinwalled cavity formations. The disease seems to preponderantly involve upper lobes, but other parts of the lung field may also be affected. Typically, it appears as unilateral or bilateral apical infiltrates progressing to cavitation. Exceptions are those cases in which the lung lesion is a part of the dissemination process. In this circumstance, the lung lesion may appear as a solitary nodule or multiple small nodules without accompanying infiltrates or cavitary formation. Fungus ball in the cavity is a rare finding having been reported only once in 37 cases. Diagnosis is made or confirmed primarily by (I) re-
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peated sputum cultures, (2) positive cultures from bronchial washings or selective brushings, (3) positive cultures from lung tissue obtained from the surgical specimen or discovered on cytologic observation, and (4) positive complement fixation or agglutination tests. Results of the serologic tests are not documented or obtained uniformly in all reported cases. These tests may have great diagnostic value, but information about their specificity and relation to the severity of the disease process is insufficient. Medical treatment of patients with S. schenkii has not been standardized. Since the classic report of DeBeurmann and Gougerot," potassium iodide therapy has been employed continuously in the treatment of all forms of S. schenkii infection. A long list of successful treatments in cases of cutaneous lymphatic sporotrichosis has been documented and the effectiveness of such treatment demonstrated, despite the fact that potassium iodide does not act directly against S. schenkii. According to in vitro studies, S. schenkii could grow in media containing 10 percent potassium iodide." Experimental data of Davis" also demonstrated that potassium iodide has no direct effect on S. schenkii, but does induce marked connective tissue reaction around the necrotic area caused by this organism. Potassium iodide was administered to 25 patients with pulmonary sporotrichosis in this collective series from the literature. In II patients this drug was used alone. The result is unknown in one case, and in spite of treatment in two patients progressive disease caused death. The rest of the patients showed improvement or cure. In the other 15 cases, iodide therapy was a part of the combined drug regimen or constituted preoperative and/or postoperative coverage. Since more effective antifungal drugs are available, efficacy of potassium iodide treatment for pulmonary sporotrichosis is difficult to evaluate at present, but it seems that only those mild cases involving pulmonary infiltrates without cavity formation responded to iodide therapy. Other antifungal drugs have been introduced and tried clinically. Because of the rarity and severity of this disease, double-bind studies could not be carried out and comparative effects of these drugs could not be determined. Griseofulvin has been employed successfully in control of the cutaneous form of sporotrichosis."- 6 One patient responded well to treatment with griseofulvin in combination with iodide. Closure of a 4 em. cavity and clearing of infiltrates were observed. Experimental therapy with griseofulvin showed no effect on the lethal outcome or the culture result of S. schenkii infection in mice." Hydroxystilbamidine has been tried but the result is hard to evaluate.
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Amphotericin B is the drug used most frequently in recent cases. Sufficient experience has been accumulated to confirm its effectiveness against a variety of fungi. Its use in controlling pulmonary sporotrichosis was shown in one reported case and in our Case 3. The linear infiltrates responded well (they disappeared) and complete cure was attained by means of amphotericin B treatment alone. In another instance, the patient had thick-walled cavities in both apices of the lung as well as a perirectal abscess caused by sporotrichosis. He received amphotericin B, which did not arrest the disease process, and eventually died. Another patient with infiltrate and a cavitary lesion improved clinically on amphotericin B treatment; however, a fungus ball developed within the cavity and culture was positive for Aspergillus. Surgical resection was refused and the final outcome was not recorded. More recently, miconazole has been tried in a patient who failed to improve on amphotericin Band flucytosine treatment. 8 Initial improvement, as evidenced by negative sputum cultures and lowering of serum agglutinin titer, was observed. Further trials are needed to assess the clinical efficacy of this drug. In the other cases, surgical intervention was necessary. Amphotericin B or other antifungal drugs were used for initial treatment and postoperative coverage. At present, it is fair to say antifungal drug therapy has achieved success in some cases but is not uniformly satisfactory. The major problem is that comparative data are lacking for setting any minimal or optimal dose of drugs to be administered for the duration of drug therapy. Surgical intervention was necessary in three patients in the reported series because the true nature of the underlying lung disease could not be ascertained. S. schenkii was isolated from the surgical specimen in one of these cases. Tissue section and smear in one of these were very suggestive of S. schenkii. Consequently, iodide therapy was initiated in both instances. In one of these the surgical specimen failed to reveal any specific diagnosis. Sporotrichosis was not uncovered until progression of the disease involving the remaining left lower lobe yielded positive sputum culture. Fifteen patients from the reported series required 17 operations. Lobectomies were carried out most frequently-seven were left upper lobectomies and three were right upper lobectomies. Pneumonectomy was necessary in two patients. Segmental resections were performed in three and combined lobectomy and segmentectomy was necessary in one. In one patient thoracotomy and biopsy were done. This was later followed by a bisegmental resection because the diagnosis had been established and the condition had progressed to
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238 lung et al.
cavitary disease in spite of medical treatment. In one patient a left upper lobectomy was performed for undiagnosed infiltrates and cavitary lesion. The disease progressed to involve the left lower lobe after the operation, and sputum cultures were positive for S. schenkii. Completion pneumonectomy was necessary. However, the patient died of progressive disease that invaded the right lung, despite treatment with multiple combined antifungal drugs. The other patients who underwent pneumonectomy also died, but as a result of the development of bronchopleural fistula and Pseudomonas infection. The other death occurred after a left upper lobectomy because of extension of the disease process to the right upper lobe, despite therapy with various combinations of drugs (amphotericin B, hydroxystilbamidine, and iodide). Thus operative deaths occurred in three; however, only one was related directly to the surgical procedure. The other two deaths were due to the inability to arrest the disease despite drug therapy and surgical resections. In another reported case, initial closure of the right apical cavitary lesion after amphotericin B therapy was noted, but a left upper lobectomy was performed because of persistent cavitary lesion. Recurrence of the disease with M. tuberculosis infection involving the left midlung field was confirmed 22 months after resection. Combined antituberculosis and amphotericin B therapy was started and the result was not mentioned. The rest of the patients had uneventful recoveries. It should be emphasized that all patients were covered by one or more drugs in the preoperative or postoperative period. From these data, we may state that surgical intervention was carried out for diagnostic or therapeutic purposes in persistent infiltrates and cavitary lesions, after medical treatment. Death was directly related to surgical intervention in one patient. Late death in two patients was attributable to progression of disease combined medical treatment and surgical resection. Recurrence of disease was observed in another patient who also underwent resection, but the outcome was not recorded. Our surgical experience is with three patients, two of whom underwent surgical resection with uneventful recoveries. The other patient's condition was complicated by concomitant pulmonary tuberculosis and left apical cavities. He was not considered to be a candidate for resection because of severe pulmonary functional impairment. Thoracoplasty was done in stages as a lifesaving procedure to ameliorate repeated massive hemoptysis. The cavities were successfully collapsed. The patient showed marked improvement and was discharged in spite of positive sputum cultures for S.
Thoracic and Cardiovascular Surgery
schenkii. Unfortunately, he was very uncooperative since he had a chronic drinking problem, and was lost to follow-up. The final outcome is unknown. The patient with small cavities and infiltrates was successfully managed with amphotericin B, as evidenced by clearing of the infiltrate and closing of the cavities. Summary
I. Pulmonary sporotrichosis is a severe pulmonary infection. Medical treatment is successful in mild cases involving pulmonary infiltrates alone or small cavities. 2. With medical treatment alone, fatal outcome was observed in six cases. Various antifungal drugs have been tried, but adequate dosage and duration of the therapy have not been standardized. The result of therapy was not uniformly satisfactory. 3. Surgical intervention is indicated: with undiagnosed pulmonary infiltrates or pulmonary cavities; in persistent infiltrates with cavitary lesions after medical treatment in suitable candidates; and in the treatment of associated pulmonary lesions such as cavitary pulmonary tuberculosis. Surgical principles to be observed in the management of pulmonary sporotrichosis follow: I. Resection is the procedure of choice. The magnitude of resection ranges from segmental resection to pneumonectomy, depending on the extent of the disease. Clean resection is necessary. 2. Antifungal drug therapy-preferably with amphotericin B-is advisable preoperatively and postoperatively, since the major cause of late death is progression of the disease when clean resection has not been feasible. 3. Surgical resection combined with drug therapy can be curative, in physiologically operable and anatomically resectable disease without increased risks. REFERENCES
2
3 4 5
6
Michelson E: Primary pulmonary sporotrichosis. Ann Thorac Surg 24: 83, 1977 DeBeurmann L, Gougerot H: Associations morbides dans les sporotrichosis heme observation de sporotrichose. Bull Soc Med Paris 24: 591, 1907 Emmons CW, Binford CH, Utz JP: Medical mycology, ed 2, London, 1963, Henry Kimpton, p 368 Davis OJ: The effect of potassium iodide on experimental sporotrichosis. J Intern Dis 25: 124, 1919 Gonzalez OAG: Griseofulvin in Systemic Mycosis, Conference on Medical Mycology, New York Academy Science, 1960 LaTapi F, LaValle P, Novles J, Ortiz Y: Griseofulvin en micosis cutaneas profundes. Dermatologia (Mexico) 3: 34, 1959
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7 Tsubura E, Schwartz J: Treatment of experimental sporotrichosis in mice with griseofulvin and amphotericin-B. Antibiot Chemother 10: 753, 1960 8 Rohwedder JJ, Archer G: Pulmonary sporotrichosis. Treatment with miconazole. Am Rev Respir Dis 114: 403, 1976 ADDITIONAL REFERENCES Baum GL, Donnerberg RL, Stewart 0, Mulligan WJ, Putman LR: Pulmonary sporotrichosis. N Engl J Med 280: 410, 1969 Beland JE, Mankiewicz E, MacIntosh OJ: Primary pulmonary sporotrichosis. Can Med Assoc J 99: 813, 1968 Chantemesse and Rodriques: Quoted in DeBeurman L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Comstock C, Wolson A: Roentenology of sporotrichosis. Am J Roentgenol 125: 651, 1974 Cruthirds TP, Patterson DO: Primary pulmonary sporotrichosis. Am Rev Respir Dis 95: 845, 1967 DeBeurmann L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Deleixhe E: Un cas de sporotrichose pulmonaire. Rev Med Liege 11: 444, 1956 D'Hanoi S: Quoted in DeBeurmann L, Gougerot H: Les sporotrichose. Bull Soc Franc Dermat Syph 23: 249, 1912 Dominguez: Quoted in Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Edgahl A: Chronic non-tuberculous disease of the lung with a report of a case of fungous infection of the right lung, probably the Sporotrichum schenckii. III Med J 61: 422, 1932 Evers RH, Whereatt RR: Pulmonary sporotrichosis. Chest 66: 91,1974 Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Formicola P: Pulmonary sporotrichosis in man, a case. Morgagni 74: 1591, 1932 Khan FA, Guarneri JJ, Sierra MF: Primary pulmonary sporotrichosis complicated by perirectal abscess. Am Rev Respir Dis 112: 119, 1975
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Kinas HY, Smulewicz JJ: Primary pulmonary sporotrichosis. Respiration 33: 468, 1976 Kluge RM, Hornick RB: Sporotrichosis. An unusual disseminated cutaneous case and a fatal pulmonary case. South Med J 69: 855, 1976 Liu CL: Sporotrichosis. Report of a case. Chin M J 73: 330, 1955 McGavran MH, Kobayashi G, Newmark L, Newberry M, Miller CA, Harford CG: Pulmonary sporotrichosis. Dis Chest 56: 547, 1969 Mohr JA, Patterson CD, Eaton BG, Rhoades ER, Nichols NB: Primary pulmonary sporotrichosis. Am Rev Respir Dis 106: 260, 1972 Nicaud: Quoted in Forbus WD: Pulmonary sporotrichosis. Am Rev Tuberc 16: 599, 1927 Post GW, Jackson A, Garber PE, Veach GE: Pulmonary sporotrichosis. Dis Chest 34: 455, 1958 Ridgeway NA, Whitcomb FC, Erickson EE, Law SW: Primary pulmonary sporotrichosis. Report of two cases. Am J Med 32: 153, 1962 Scott SM, Peasley ED, Crymes TP: Pulmonary sporotrichosis. Report of two cases with cavitation. N Engl J Med 265: 453, 1961 Serstock OS, Zinneman HH: Pulmonary and articular sporotrichosis. Report of two cases. JAMA 233: 1291, 1975 Siegrist HD, Ferrington E: Primary pulmonary sporotrichosis. South Med J 53: 728, 1965 Singer JJ: Pulmonary sporotrichosis, report of two cases. Am Rev Tuberc 18: 438, 1928 Smith AG, Morgan WKC, Hornick RB, Funk AM: Chronic pulmonary sporotrichosis. Report of a case, including morphologic and mycologic studies. Am J Clin Pathol 54: 401, 1970 Smith DT: The Chest, Myers, McKinlay, eds., Springfield, Ill., 1949, Charles C Thomas, Publisher Trevathan RD, Phillips S: Primary pulmonary sporotrichosis. JAMA 195: 965, 1966 Voss JA: Case of sporotrichosis of lungs. Nor Mag F Laegevidensk 96: 14, 1935