Recurrence of allergic bronchopulmonary aspergillosis after seven years of remission

Recurrence of allergic bronchopuhonary aspergillosis after seven years of remission J. Michael Halwig, and Roy Patterson,

M.D., Paul A. Greenberger, M.D. ~‘hi(‘~~s~<>, I;!

ABPA is characterized by asthma, peripheral blood eosinophilia, and a history or presence of pulmonary infiltrates. ’ Immunologic characteristics include immediate skin reactivity to Af, increased total serum IgE,” precipitating antibody against Af, and increases in IgE and IgG antibodies against Af that can be recorded by calculation of an index.” Proximal saccular bronchiectasis can be demonstrated by tomograms when that pulmonary damage has occurred. ’ A system of staging of ABPA has been presented to assist in the evaluation and management of ABPA.” These stages include an acute stage with pulmonar) infiltrates. eosinophilia, and elevated total serum IgE that responds to corticosteroids. The remission stage is free of infiltrates with a stable total serum IgE. The exacerbation stage is characterized by recurrent pulmonary infiltrates in the absence of other etiologies and a rise in total serum IgE. The CSD asthma stage is characterized by CSD asthma with or without exacerbations of ABPA. The fibrotic stage is an advanced stage of fibrotic roentgenographic abnormalities with asthma and irreversible obstructive pulmonary function changes. We present a case in which recurrence of ABPA developed after 7 yr of remission to demonstrate that

From the Section of Allergy-Immunology, Department of Medicine, Northwestern University Medical School, Chicago, Ill. Supported by National Institutes of Health grant Al L 1403, the Ernest S. Bazley Grant, and the Chicago Lung Association. Received for publication Ian. 23, 1984. Accepted for publication April 19, 1984. Reprint requests: Roy Patterson, M.D., Northwestern Unlvenity Medical School, 303 E. Chicago Ave., Chicago, IL 60611 *Present address: 2045 Peachtree Road. N.E., Atlanta, GA 30309. 738

ABPA: At’: CSD: IgE-Af: IgG-At’:

M.D., Marshall

Levine,

M.D., *

Allergic bronchopulmonary aspergillosis Asprgillus futnigntu.s Corticosteroid-dependent Specific IgE antibody activity against .4f Specific IgG antibody activity against Af

patients with diagnosed ABPA are at risk for recurrences for a prolonged period of time. CASE REPORT The patient is a 3?-year-old white woman with a histoq of ABPA initially diagnosed in 1975 after a history of wheezing, intermittent bronchitis. and recurrent pulmonary infiltrates. Complete white blood cell count was 7100/n? She demonstrated a prick positive skin reaction to Af with a total serum IgE of 3700 ngiml and positive precipitins to Af (Fig. I). ELISA for IgE-Af and IgG-Af was performed as previously described.” The results are reported as an index of the patient’s values divided by the asthma pool.:’ The index is considered positive when it is more than twice the asthma pool. IgE-Af index was negative, and IgG-Af index was positive at this time. Bronchography demonstrated central bronchiectasis of the superior and lingular regions ot the left lung consistent with ABPA. She was treated with 30 mg of prednisone per day for I wk with maintenance on alternate day therapy at the same dose. Prednisone was tapered and stopped in November 1976. Fig. I illustrates serial changes in total serum IgE. precipitins to Af. and IgE-Af and IgG-Af indices over a i-year interval with subsequent roentgenograms demonstrating resolution of the previous infiltrates including roentgenograms obtained with maximal elevations in total serum IgE.

VOLUME 74 NUMBER 5

Her ,
DISCUSSION Management of ABPA can be difficult due to the insidious and variable course of the disease. There are a wide spectrum of clinical patterns and a variable period of time from onset of disease to diagnosis.’ Exacerbations of ABPA may produce dyspnea, productive cough, malaise, and fever, but the pulmonary infiltrates can occur with minimal or no symptoms of clinical disease. In a retrospective review of ABPA, approximately one third of patients were noted to be asymptomatic during periods of pulmonary consolidation.” Untreated disease with recurrent pulmonary inflammation may lead to progressive pulmonary destruction including proximal bronchiectasi? and may result in pulmonary fibrosis.Y The total serum IgE has proven useful in follow-up of patients with ABPA.“’ The IgE level declines after initial institution of prednisone therapy. ’ ’ Exacerbations of ABPA are determined by the presence of pulmonary infiltrates without other apparent etiology in association with increased total serum IgE.” This patient had previously documented ABPA with resolution of asthma, fall in serum-IgE levels, and clearing of pulmonary infiltrates occurring after treatment with prednisone. In May 1978 the total serum IgE nearly doubled, and IgE-Af and IgG-Af indices became elevated during an episode of wheezing. However, a chest roentgenogram did not demonstrate any infiltrates to confirm the presence of a flare of ABPA. In March 1983 she then developed

Recurrence

of allergic

bronchopulmonary

aspergillosis

739

FIG. 1. Exacerbation of ABPA after a remission of 7 yr with a recurrent pulmonary infiltrate and concurrent elevation of serum total IgE with corresponding precipitins to Af and IgE-Af and IgG-Af indices.

ACUTE DIAGNOSIS

61 TREATMENT (STAGE

W;:“,“:;;

A\

,

WITH

PREDNlSONE

I)

RECURRENT

--,

(STAGE

CORTICOSTEROID DEPENDENT

EXACERSATlCN III)

ASTNMA

EXACERSATlclNS (STAGE

,..”

WlTN OF

ASPA

IV)

...*’

...f i FIBROTIC LUNG DISEASE (STAGE

k....e’*

VI

FIG. 2. Stages of allergic bronchopulmonary aspergillosis. The so/id arrows indicate demonstrated progression of patients through these stages. The dashed arrow indicates a presumptive path of progression to fibrotic lung disease. (Modified from Patterson R, Greenberger PA, Radin RC, et al: Ann Intern Med 96:291, 1982.)

recurrent asthma, elevation in total serum IgE, and recurrence of an infiltrate after a 7-year interval. Treatment with prednisone was associated with resolution of symptoms, fall in serum IgE, and subsequent clearing of the infiltrate.”

740

Halwig

et al.

We are unaware of any prolonged remisbron as in this patient. which was followed by a recurrence 01’ ABPA. The mechanism is unclear, but the presence of IgE and IgG antibodies to Af alone cannot account for the flare. The significance of this patient’s relotation from Chicago to Georgia in 19X1 to the recur rence of ABPA and asthma is uncertain. It has been demonstrated previously that exacerbations of ABPA are associated with the level of totat outdoor mold counts in that over three quarters of flares in Chicago occurred from June through November ” At present the relationship of this patient’s rntercurrent pregnancy to her subsequent recurrence of ARPA is uncertain. The effect of pregnancy on the course ot asthma has been previously revievved and remains to be we11 characterized.” The effect of pregnancy on exacerbations of ABPA has not been clearly established and requires further investigation. Effective management of ABPA ~ncludcs assess ment of clinical symptoms, serial determinations of serum-IgE levels, and frequent chest roentgenographs in order to identify symptomatic and asymptomatic infiltrates. Classification of patients with ABPA by a staging system can provide assistance in identification and management of disease (Fig. 21 The case we have presented emphasizes the need for continued follow-up of patients in remission with serial-IgE levels and roentgenographs to identify and manage recurrences of disease.

Patlerwn

R, Grernbrrger

~nunoassay 4nn Intern 4

<

loir\i, i’hes: (ifI presi 3 Patterson R. Greenberger

M. Patterson

R, Mmtzet

R, et al: Clinical

i:hopulmonary T

L.

:t li

‘2 ,Gii,ir:i aspe:gi/io\ts

Ricketti

AJ.

aspet-gillosi\.

RC.‘, et al. Aher+.

Application in diagnosis

I Lab Clin

Greenberger

PA.

hrort-

as an aid to management of enzyine-iinhcci of allergic bron-

Med

Patterson

99:288.

1982

R: Varying

prrsemi-

iions of allergic hronchopulmonary aspergillosis Int ,irch Al!ergy Appl Immunol 7?.283. 19x4 .< Safirstein BH. D’,%ura MI, Simon 6. et ai, Five-ye,tr tollou

It).

up of allergic

bronchopuhnonary

l-h

107

1OP~4Sll ._.

Rickcttt

4.1. (ireenhergcr

aspergillosis.

PA.

Patterson

tmporrant ,ttd in management d5pei-gilloii5 j .+ti l.fK(+\ fl.!Y iI

12.

I,@ value

as an indicator

!:v J Pediatr ! I +l.l, irheau SA. Nichols

IgE r+s rai

bronchopuimonary 7463, 1984

and predictor

Radin

D.

Flaherty

to!

h.?:‘)I

KC‘. Grecnberger

PA.

of allergic

Gin Allergy 13 271. 198’ Turner ES. Creenherper P4, t:regnan!

asthmatic

of disease

acts\ -.

197’

D, et dl. Relattonshtps

t\*een predntsone therapy, disease activity IpE jc\el in allcrgtc bmnchopulmonary

13

R. Serum

of allergic IhlMLYOI

.Am Rev Respir

Rosenberg kl. Patterson R. Roberts M: Immunologic rz ,ponae\ to therapy :n allergic bronchopulmonary aspergiliosis. serum

and in-

for the diagnosis of allergic hronchopulmo Ann Intern Med 86405. 1977

Radm Gaging

.2nn Intern Med 96:286, 1982 6. Greenberger PA. Patterson R ;mmunosorbenl ashy (ELISAt

,.nd exa
munoiogic criteria nary aspergillosis.

PA

,tq?crgillosis

i ,<<,I C‘I 1:. fhlMi

I. Rosenberg

Kiiketti

Mend&on EB. F&her MR. Mmtzer RA. et ‘iI: Ratii:rgrapn~~, .md clinical staging of allergic hronchopuhnonary a,perpii

.hopulnmxtr~

!5 I..

REFERENCES

P.Z

index for allergic bronchopulnron~y Med 99.1X. IOX:

Iiatien!

he-

and the total serumaspergillosi\. J AI

197x

Patterson

R. et al: Mold

bronchopulmonary Patterson 4nn

Intern

K: Management Med

count:~

aspergillosia

6905.

or’ the 1980