Blastomycosis in Northeast Tennessee

Blastomycosis in Northeast Tennessee* Jose E. Vasquez, MD; Jay B. Mehta, MBBS, FCCP; Rajesh Agrawal, MD; and Felix A. Sarubbi, MD

Study objectives: To study the epidemiologic and clinical features of blastomycosis in northeast Tennessee. Design: Retrospective review of blastomycosis cases in the region from 1980 through 1995. Setting: Hospitals located in the Tri-Cities region of northeast Tennessee. Patients: Seventy-two patients with confirmed blastomycosis infection. Interventions: None. Results: During the 1980 to 1995 study period, we documented 72 cases of blastomycosis. The mean age was 52 years (range, 13 to 86 years), most were male (69.4%), and nine were immunocompromised. A possible environmental exposure was noted for 28 patients. Pulmonary involvement represented the most common site of infection (61 cases), but multiorgan involvement was common (17 cases). Most patients with pulmonary blastomycosis (66%) presented with a chronic illness, and radiologic findings usually revealed local consolidation or a mass-like lesion. Nine patients developed ARDS with an associated mortality rate of 89%, compared with a 10% mortality for non-ARDS pulmonary cases. Antifungal treatment regimens varied widely, with amphotericin B often used for sicker patients. An epidemiologic evaluation revealed that the mean yearly incidence rate for blastomycosis quadrupled between 1980 and 1987 (0.31 cases/ 100,000 population) and 1988 to 1995 (1.23 cases/100,000 population) (p=0.00001). Most new blastomycosis cases in the 1988 to 1995 period occurred in three counties in the region where significant new construction projects have been underway. Conclusion: Blastomycosis is endemic in northeast Tennessee and the number of cases is increasing, coinciding with major new construction in the region. Clinicians in the area must be alert to this condition. (CHEST 1998; 114:436-443) Key words: adult respiratory distress synd rome; Blastomyces dennatitidis; blastomycosis; endemic mycosis; epidemiology

T dennatitidis, he dimorphic soil dwelling fungus , Blastomyces

is the agent of blastomycosis, a systemic mycosis that is endemic in different parts of the world but particularly so in th e south-central and midwestern United States. Most cases of blastomycosis in humans appear to result from the inhalation of aerosolized spores into the lungs where they transform into yeasts and elicit a characteristic pyagranulomatous response. 1 From here, the organism can disseminate to a variety of extrapulmonary sites. Although a variety of reports dealing with sporadic and epidemic cases of blastomycosis in rural 2 - 7 and urban settings 8 ·9 have been published, the epidemi*From the James H. Quillen Veterans Affairs Medical Center (Drs. Vasquez, Agrawal, and Sarubbi), and the Divisions of Infectious Diseases (Drs. Vasquez, Agrawal, and Sarubbi) and Pulmonary Medicine (Dr. Mehta), Department of Internal Medicin e, East Tennessee State Unive rsity College of Medicine, Johnson City. Manuscript received October 20, 1997; revision accepted Janumy 7, 1998. Correspondence to: Jose E. Vasquez, MD, Department of Internal Medicine, Box 70622, James H. Quillen College of Medicin e, East Tennessee State University , Jolwson City, TN 37614

436

ology of this fungal infection in the United States is not well described. Blastomycosis is not a reportable disease to the Centers for Disease Control and Prevention and there is no reliable skin test or serologic test to confirm infection in particular populations.l0-12 A few studies have been published repmting on the occurrence of blastomycosis in different ende mic areas,13-16 and regional rates are available for certain states 17-19 but not for Tennessee. Based on our experience with blastomycosis in the northeast Tennessee region, particularly over the past decade, we decided to investigate more thoroughly the occurrence of this fungal infection in our geographic area. We found 72 cases of blastomycosis for the period 1980 to 1995 with the majority of cases diagnosed during the years 1988 to 1995. This latter time period coincided with considerable construction activity in this developing region of the country. MATERIALS AND METHODS

A variety of efforts w ere directed toward identifying cases of blastomycosis in the northeast Tennessee region for the period of Clinical Investigations

January 1980 through December 1995. Methods used to identify cases and to collect data were approved by the East Tennessee State University Institutional Review Board and the instih1tional review boards at specific hospitals. Since a number of hospitals in the state forward positive fungal culh1res to the State of Tennessee Health Department Laboratory in Nashville for specific organism identification, we contacted this laboratory and obtained a list of patients who were defined as culture positive for B dermatitidis. Listed patients who received care at one of several major northeast Tennessee hospitals were identified and their medical records were examined. Microbiology and pathology records at these hospitals were also reviewed for additional culh1re-proven cases of blastomycosis as well as cases confirmed by the presence of typical, single broad-based budding yeasts with a thick, doubly contoured cell wall observed in clinical specimens submitted for histologic, <:ytologic, or potassium hydroxide digestion examination . The medical records for these cases were reviewed as were the records for patients coded for any type of blastomycosis infection. The following northeast Tennessee hospitals were included in the study: James H. Quillen Veterans Affairs Medical Center, Johnson City Medical Center and North Side Hospital in Johnson City (1995 population, 50,500), Bristol Regional Medical Center in Bristol (1995 population, 40,000), and Holston Valley Hospital and Medi.cal Center in Kingsport (199.5 population, 40,000). These facilities serve a patient population in northeast Tennessee, southwest Virginia, western North Carolina, and southeastern Kentucky. The three cities mentioned form the major urban conglomerate in the region referred to as the Tri-Cities area. A standard data collection form was used to record clinical and epidemiologic data. Whenever possible, attempts were made to include at least a 6-month postdiagnosis follow-up period. This involved conducting telephone calls to patients and their physicians as well as reviewing outpatient records and autopsy reports. Previously published criteria for ARDS 20 and immnnosuppression21 were used. Statistical data on population and constmction activities, including building permits for ~$10,000 struch1res in northeast Tennessee, were obtained from specific sources.22 •23 The overall study period (1980 to 1995) was divided into two equal segments that are referred to as an "early period" (1980 to 1987) and a "late period" (1988 to 1995). The late period included the years of greatest constmction activity. Statistical analysis was conducted using the x2 test (Epi Info, Version 6; USD Inc; Stone Mountain, Ga). p values <0.05 were considered to be significant.

RESULTS

Seventy-two patients were found to have infection caused by B dermatitidis during the study period and 58 of these (81 %) were culture positive. General characteristics of the 72 patients are shown in Table 1. Patients ranged in age from 13 to 86 years (mean:±:SD age=52:±:17.8 years) and the majority (69%) were male. Although none of the patients were known to be HIV infected, serologic testing for HIV was done in only seven cases. Nine patients (13%) were considered immunosuppressed at the time of infection with B dermatitidis, including single cases of each of the following: lung cancer and corticosteroid use, a 32-week pregnancy, alcohol use and chronic liver disease, cerebral lymphoma and corticosteroid

Table !-General Characteristics of 72 Patients With Blastomycosis Diagnosed in Northeast Tennessee Variable

No. of Patients(%)

Male Female White l mmunosuppressed Diabetes mellitus State of residence Tennessee Virginia Kentucky North Carolina

50 (69.4) 22 (30.6) 64 (88.9)

9 (12.5) 16 (22.2)

55 (76.4) 13 (18.0) 3(4.2) 1 (1.4)

use, vasculitis and cyclophosphamide plus corticosteroid use, chronic lymphocytic leukemia, and transitional cell bladder cancer and systemic chemotherapy. Two additional patients had rheumatoid arthritis and chronic bronchitis and were using corticosteroids. Figure 1 shows the number of cases identified during the study period. Nineteen (26%) were noted in an early period (1980 to 1987) and 53 (74%) were identified in a late period (1988 to 1995). Patients living in three northeast Tennessee counties (Washington, Sullivan, and Unicoi) essentially accounted for the rise in the total number of cases seen in the region during the late period. Table 2 summarizes the distribution of blastomycosis cases for patients residing in northeast Tennessee counties in the early and late periods. Incidence rates are also listed. Noteworthy increases in incidence rate were documented in Washington County (includes Johnson City), Sullivan County (includes Kingsport and Bristol), and Unicoi County, which is just south of Washington County. Although most patients resided in a rural setting, an increase in the number of urban cases was seen in the late period. During the early period, only one patient lived in one of the Tri-Cities whereas in the late period, 13 patients lived in one of these three cities and 10 were in Johnson City (Fig 2). Five of the 10 Johnson City cases lived in close proximity to a construction site, 3 had an occupational exposure to soil, and no definite environmental exposure was noted for 2 patients. None of the Johnson City cases shared a common exposure source. Exposure-prone occupations for the patient population included farming (nine), constmction work (five), mining (five), carpentry (two), and heavy equipment operation (two). Forty-two patients engaged in apparently lower-risk occupations, including teaching, homemaking, store clerk, etc. The occupation for seven patients was unknown. Among CHEST 1114 I 2 I AUGUST, 1998

437

12 ~~------------------------------.-----~

• Other counties in region 1o

(/)

•

Sullivan County, TN

0 Washington County, TN 0 Unicoi County, TN

8

c

Q)

-

~ 6 0.. 0

~

4

2 0

80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 Year

FIG URE l. Cases of blastomycosis diagnosed in north eas t T ennessee h·om 1980 through 1995. Bars re prese nt th e numbe r of new eases diagnose d eaeh year. Cases invo lving patie nts From th ree north east T e nn essee eounties (Washing ton , Sullivan , and Unieoi) oceurred almost exclu sive ly dnring the la te p e riod.

the lower-1isk occupation group, five patients engaged in hunting (four) or camping (one ) and thus had a possible recreational exposure to blastomycosis in the environm ent. No seasonal prevalence was identifi ed when cases were analyzed by month of onset of symptoms. Figure 3 shows the clinical spectrum of blastomycosis in the 72 patients by organ involvement. Lungs

we re the most frequent site of infection (61 cases, 84.7%), but different combinations involving skin, bone/joint, prostate, and la1ynx were also seen. A chronic presentation (:=:::::4-week history of symptoms ) occurred in 40 of 61 patients (66%) with pulmonary blastomycosis. The following were the most common symptoms among patients with pulmonary involvement: cough (75%); weight loss

Table 2-Distribution of Blastomycosis Cases by County of Residence in Northeast Tennessee * Early Pe1iod ( 191>0-1987 )

Late Pe ri od (1988-1995)

County

No. of Cases (Popu lation )t

Yearly Tn cidPnce Rate

No. of Cases (Population )t

Yearly Incicle ncc Hate

p Valu e

Odds Hatio (95% CL)t

Ca1te r Cocke Gree ne Hawkin s John son Sulli van Un icoi Washington Total

l (.50,20.'5 ) 1 (2 8,792) 5 (5 4,422 ) 2 (4:3,75 1) 1 (13,74.5 ) 0 (143,968) 0 (16,362 ) 1 (88,7.5.5 ) ll (440,000)

0.25 043 1.1.5 0.57 0.91 0.00 0.00 0.14 0.31

4 (5 1,505) 1 (29,141) 5 (.5.5,853) 6 (44,.565 ) 0 (13,766) .5 (14:3,.596 ) 4 (16,.549) 19 (92,3 1.5) 44 (447,290 )

0.97 0.43 1.12 1.68 0.00 0.44 3 .02 2 .57 . 1.23

0. 11>9 0.993 0.967 0.16.5 0.3 17 0.02.5 0.047 0.00008 0.00001

3.90 (042, 91.57) 0.99 (O 03 , 36.04) 0.97 (0 25, 3.86 ) 2.9.5 (0 .54, 21 0."5 ) 0.00 (0.00, 17.28) U nde £ln ed Undefin ed 18.27 (2 61, 366 52) 3.93 (1.96, 8 07)

*N ulllhe r o f cases and yearly in cidence rate pe r 100,000 population for each pe riod. tThe county populations fo r tlw early pe1iocl and late period are those co rrf's pondin g to 1980 and 1990 census data, respectively. ! 9-5% C L= 9.5% con fidence limits.

438

Clin ical Investigations

KENTUCKY

VIRGINIA !;,. !;,.

D

BD

D

M

!;,. !;,.

D

D

D./!£

~~

!;,.

~

tP6 TENNESSEE

m

DO

06.

2

!;,.

6b

D

M!':fb !;,.

!;,.

M

M

06. !;,.

NORTH CAROLINA

o Early (1980-1987), .6. Late (1988-1995) j

D

FIGURE 2. Reside nce of pati e nts with blastomycosis, classifi ed by p e riod of d iagnosis ("ea rly," from

1980 through 1987; or "late," from 1988 through 199.'5). The Tri-C ities area is shown with encircled numbers: 1, Johnson C ity; 2, Bristol; 3, Kingsport.

(57%); fever (49%); dyspnea (46%); chest p ain (31%); hemoptysis (23%) ; night sweats (26%); and chills (18% ). Local consolidation and mass-like lesion(s) were the most common findings on chest radiograph (Table 3). Nine patients developed ARDS (Table 4). Only one of these patients was immunosuppressed and the fatality rate for this group was 89%. Two of our nine ARDS cases were previously presented elsewhere.24 Among patients with non-ARDS pulmonary blastomycosis, the fatality rate was 10%.

Twenty-three patients had cu taneous blastomycosis with a total of 42 lesions that evolved insidiously. Verrucous and ulcerative-type lesions predominated and these occurred at such sites as the face , trunk, and extremities. One blastomycosis skin abscess oc-

Table 3-Radiologic Presentation for 61 Patients With Pulmonary Blastomycosis According to Clinical Presentation, Chronic vs Acute Chest Radiograph

Pulmonary

Prostate

Skin

45

Larynx

Bone/Joint

F IGUHE 3 . C linical spectrum by organ involve me nt of 72 pati e nts with blastomycosis.

Local consolidation Mass-like lesion Diffuse alveola r infiltrates Cavita1y lesion (s) Diff'nse milimy infiltrate Pe rihil ar infiltrate Bibasilar nodu les Solitmy nodu le Norm al chest radiograph t Pleural e ffu sion Unknown

Total (n = 61 )

CPB* ( n =41 )

APB* ( n =20)

17 14 8 6 6 4

13 9 3 5 3 4 0

4 5 5

l

1 l

1 2

l 0 2

l 3 0 1 0 0

0

*CPB =chronic pu lm onary blastomycosis (2:4-wk histmy of symptoms ); APB =acute pu lmona1y blastomycosis (< 4-wk histmy of symptoms). t A 62-year-old patient "~t h ch ronic lymphocytic leukemia presented ~th 2-month histmy of congh, normal chest radiograph , and B dennali.lidis grew from the spntum cnltnre. CHEST I 114 I 2 I AUGUST, 1998

439

Table 4-Clinical Findings for Nine Patients With ARDS Due to Pulmonary Blastomycosis Pati ent No./ Age, y r/Scx 1/39/F 2183/F 3/71/M 4/79/F .'5/61/F 6/34/ M 7/72/M 8/26/F 9/51/F

Underlying Disease* DM Arrhythmi a PnPtlm oeoniosis

DM ,HTN HTN,CA D None Bladde r Ca, DM t None HTN

Recent Exposure

Le ngth of Til ness,

No No No No No Yes No No No

6

wk

1 1 4

8 3

Extrapu lmona1y l nvolve ment

Amphoteri cin B T otal Dose, mg

Outcome

Larynx Skin Skin None None None None None None

70 125 30 0 2,000 730 0 40 0

Died Died Died Died Recovered Died Died Died Died

*DM = di abetes mellitus; IITN =syste mic hype rtension; CAD = coronary artery disease; Ca = cancer. t Pati ent 7 had r cee ntly received che motherapy for bladder carcinoma and was th e only immunosuppressed case of the group .

curred at an lbow e site. Two patients with skin involvement also had ARDS associated with pulmonary blastomycosis. Bone involvement due to blastomycosis occurred in fo ur patients at the following sites: calcaneus , tarsal bone , thumb phalanx, and tibia. Patients reported chronic complaints concerning the involved site and th ey presented with or without pulmonary or skin involvement (Fig 3). Two patients had septic arth1itis due to blastomycosis: one patient presented with a 4-day history of a wollen s and tender ankle, and Gram 's stain of ankle joint fluid showed suspicious yeasts (Fig 4, Bottom ), and the culture g rew B dermatitidis . The second patient presented with a 4-month history of knee pain, and culture of synovial fluid also grew B dernuttitidis. Each of these six patients was immunocompetent and none developed ARDS . Prostate infection due to B d errnatitidis occurred in two patients . One patient had multiple skin lesions, hemoptysis, and a hilar mass on chest radiograph as well as prostatitis and epididymitis. Prostate biopsy specimen showed microabscesses with typical budding yeast forms consistent with B clermatitidis . A second patient with skin lesions and prostatitis was culture positive for B d ermatitidis from a cutaneous site, and a prostate biopsy specimen showed budding yeast forms typical for th e organism . In a few patients , use of a specimen Gram's stain initially raised suspicion of the presence of blastomycosis (Fig 4). Serologic testing for blastomycosis was perform ed in 29 patients . Twenty-four patients unde1went complement fixation testing and six were positive (2: 1:8 titer). Fourteen patients unde1went immunodiffusion testing and four were positive. Therapeutic interventions for the 72 patients varied considerably. Five patients received no therapy; three with ARDS died prior to diagnosis and two with other underlying conditions also died b efore 440

treatm ent could be offered. Treatment was unknown for two patients and one patient received miconazole . Three patients underwent removal of the infected pulmonary lobe and two of these received subsequent antifungal therapy (ketoconazole in one and itraconazole in one). Two patients known to have

FIGURE 4. Top : Gram 's stain of suction ed sputum from patient 7 in Table 4 howing s a large, weakly staining, Gram -negative single broad-based budding yeast. Multiple segmented n eutrophils ami a small Gram -positive Candida yeast are a lso seen (o rigin al magnification X 1,000 ). Th e fun gal culture yjelded B dennatitidis . Bottom: Gram's stain of ankle fluid aspirated fi-om anoth e r patient showing Gram-n egative, single broad-based budding yeas ts (ori ginal magnification X 1,000). Th e fun gal culture yjelded B dennatiUdis.

Clinical Investigations

pulmonmy blastomycosis were simply observed but then w ere treated when their symptoms persisted. The remaining 59 patients received antifungal therapy from the time of diagnosis: amphotericin B alone (18), amphotericin B followed by ketoconazole (7), amphotericin B followed by itraconazole ( 5), ketoconazole alone (18), and itraconazole alone (ll) . In the amphotericin B alone group, there were five patients with ARDS and all of these died. Excluding the group with ARDS , in which several patients received only a few doses of amphotericin B, the amphotericin B alone population included 13 patients with pulmonary disease and 3 of these also had cutaneous involvement. The mean total dose of amphotericin B was 1,633 mg and the mean follow-up period was 31.1 months . Nine patients recovered, one died as a r esult of the B demwtitidis infection, and the outcome for three patients was unknown. The ketoconazole alone group (mean daily dose =444 mg) included p atients with pulmonary (six), pulmonary plus other sites (t hree) , cutaneous (six), cutaneous plus other nonpulmonary sites (two), and bone-joint (one) infections. Twelve of these patients recovered over a m aen follow-up period of 37.6 months. Five patients suffered r elapses (27.8%), including two with cutaneous-only sites. The outcome for one patient was unknown. Eleven patients received itraconazole alone ( mean daily dose= 291 mg) and infection sites included lung (eight), lung plus cutaneous (two), and lung plus cutaneous and bone-joint (one) . T en p taients recovered over a mean follow-up period of 16.9 months and one died with large cell lung cancer 6 months after initiating antifungal therapy. Overall, 14 of the 72 patients died (19.4%) within the first 6 months of diagnosis. Twelve of the deaths (16.7%) were attributable to blastomycosis (eight of these had ARDS) and two patients died of causes related to underlying neoplasia (b rain lymphoma in one, lung cancer in one) .

DISCUSSION

Blastomycosis is endemic in the northeast Tennessee region and the incidence of symptomatic cases has risen in recent years. Although an increased awareness of the disease on the part of physicians in the area and perhaps a b etter utilization of diagnostic measures might have accounted for part of this observation, it remains quite noteworthy that the mean annual incidence rate for blastomycosis quadrupled b etween the 1980 to 1987 early period (rate =0.31 cases/100,000 population) and the 1988 to 1995 late period (rate = 1.23 cases/100,000 population) (Table 2). Of interest in the early period was

the occurrence of 10 blastomycosis cases during the years 1981 to 1982 (Fig 1). However, this infection trend was not sustained over the ensuing years (1983 to 1986) and the 10 cases were widely dispersed among various nmtheast Tennessee and southwest Virginia counties. In contrast, the documentation of blastomycosis infections during the late pe1iod was a sustained observation that included a number of cases from specific northeast Tennessee counties. In particular, infection rates for Washington County, which includes Johnson City; Sullivan County, which includes Kingsport and Bristol; and Unicoi County, which is just south of Washington County, increased considerably from the first to the second study periods (Table 2). It is conceivable that the greater number of blastomycosis infections documented during the 1988 to 1995 period in these three counties was related to major new construction projects in the region over the past 10 years . These projects included the building of an interstate highway that passes through Johnson City and extends south toward North Carolina, other local highway construction, and a variety of residential, commercial, and school building projects. Wediscovered that for six of the eight counties in northeast Tennessee (Carter, Cocke, Johnson, Sullivan, Unicoi, and Washington) , building permit offerings nearly tripled during sample years in the late period compared with sample years in the early pe1iod. The experience in Johnson City is worthy of further comment since there were no cases of blastomycosis infection recorded in this location for the 1980 to 1987 period but 10 cases w ere documented during the 1988 to 1995 period. Interestingly, the number of building permits secured in Johnson City increased from 794 in the early period to 1,759 in the late period and .5 of the 10 patients with blastomycosis during the second period reported living in an area of active construction work. Blastomycosis is uncommonly repmted in urban settings8•9 and the Johnson City experience (mean annual incidence rate=2.50 cases/ 100,000 population during 1988 to 1995) can be contrasted with the "hyperendemic" rate for blastomycosis in Rockford, Ill, where 32 cases w ere diagnosed b etween 1981 and 1989 (mean annual incidence rate =1.94 cases/100,000 population). 9 With regard to clinical, laboratory, and radiologic aspects pertaining to the 72 patients infected with B dermatitidis in our study, several points can be emphasized. The male:female ratio of 2.3:1 likely reflected an increased environmental exposure to B dermatitidis associated with certain male predominated professions such as construction work and mining. Male predominant ratios have been reported previously11 · 16 ·25 ·26 while others have noted a fairly equal distribution of cases b ygender,3 ·5 ·6 particularly CHEST / 114 / 2 / AUGUST, 1998

441

in epidemic settings. A significant underlying illness was found in 37.4% of our patients (diabetes mellitus or immunosuppressed state). The majority of the population (61 of72 patients, 84.7%) had pulmonary involvement (Fig 3) and 66% of patients with respiratory disease were symptomatic for 2::4 weeks. Interestingly, a number of these patients with persistent pulmonary disease had been evaluated by physicians in recent weeks or months and were believed to have poorly responding bacterial pneumonias. They underwent a variety of antibacterial therapies prior to having respiratory secretions evaluated for fungal and other nonbacterial pathogens. In some cases, patients with lung disease and concomitant verrucous type skin lesions were initially believed to have coincidental conditions, ie, pneumonia and possible squamous cell skin cancer until appropriate diagnostic studies revealed that the processes were linked. Clinical symptoms noted among our patients with pulmonary blastomycosis (cough, fever, weight loss, etc) were typical of findings described by others.l·11 .l 6.25·26 Unfortunately, nine of our patients developed ARDS (Table 4) and only one of them survived. This dramatic complication of pulmona1y blastomycosis, which can be associated with mortality rates in the range of 50 to 70%, has been reported previously. 27 -29 In part, we believe that the lower survival rate for our ARDS cases was related to the lack of a premortem diagnosis in three patients (diagnosed at postmortem examination) and the administration of only limited amounts of amphotericin B to another three patients who were nearly moribund when therapy started. Laboratmy studies used to diagnose infection with B dennatitidis were consistent with those reported by othersl,S,ll,2l ,25 and included special stains and fungal culture of sputum and material obtained by bronchoscopic evaluation as well as histologic examination of tissue obtained by biopsy (lung, skin, prostate) . It is also useful to point out that a careful examination of a specimen Gram's stain can also raise suspicion of infection with B dennatitidis (Fig 4). These relatively straightforward laboratory tests often yielded diagnostic information in a brief period of time and the findings were quickly incorporated into therapeutic decisions. Frequently, the major delay in diagnosis was a result of physicians not considering the possibility of blastomycosis infection rather than the time needed to conduct an appropriate laboratmy test. We found results of serologic testing for blastomycosis infection by complement fixation or immunodiffusion to be of limited assistance, a finding that has been well noted by others.l0-12 It is important to acknowledge, however, that serologic testing using an enzyme immunoassay for detection of antibody to 442

the A antigen of B dennatitidis can yield useful results in the setting of either acute or chronic blastomycosis infection30·31 and that measuring antibody against a major immunoreactive 120-kd surface protein on B dennatitidis (WI-1) may also become a useful diagnostic tooJ.3 2 Chest radiograph findings for our patients with pulmonary blastomycosis usually showed areas of local consolidation or mass-like lesions. Patterns of diffuse alveolar infiltrates or diffuse miliary infiltrates were next most common (Table 3). These results are similar to those described by others.:33·34 As expected, some patients with mass-like lesions were believed to have malignant disease and the diagnosis of blastomycosis was made at the time of lobectomy. Therapeutic interventions in our population varied considerably and ranged from lobectomy alone to amphotericin B with or without oral add-on therapy. Among patients who received a specific antifungal agent, the highest relapse rate was noted for the ketoconazole alone group, in which 5 of 17 evaluable patients (29.4%) who received a median daily dose of 400 mg for approximately 8 months failed to respond to treatment. Medication compliance was an issue for one of these five patients. All but 1 of the 11 patients treated with itraconazole alone responded favorably to therapy and the one indeterminate outcome occurred in a patient who died as a result of an illness unrelated to the blastomycosis infection. Our results obtained with ketoconazole and itraconazole regimens are similar to those published by others. 35-37 There was a tendency to use amphotericin B in the setting of more serious clinical illness, including all of the patients with blastomycosisassociated ARDS whose conditions were diagnosed prior to death. In conclusion, our report draws attention to a growing clinical experience with blastomycosis in several counties located in northeast Tennessee. Sullivan and Washington Counties include the Tri-Cities conglomerate (Kingsport, Bristol, and Johnson City) and Unicoi County includes a new highway corridor that extends south toward North Carolina. Washington County, and Johnson City in particular, accounted for 43% of blastomycosis infections that occurred in the region during the 1988 to 1995 period. New construction efforts in the area (residential, commercial, and roads) have been substantial and may have played a role in the dispersal of B dennatitidis spores . Health-care workers in this geographic area must be alert to the presence of blastomycosis and should appropriately consider this fungal infection in their Clinical Investigations

evaluation of certain patients. Finally, blastomycosis should be included among the reportable diseases in Tennessee.

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