Pulmonary alveolar proteinosis in an AIDS patient without concurrent pulmonary infection

Patients with acquired immunodeficiency syndrome (AIDS) are potentially at increased risk for developing secondary pulmonary alveolar proteinosis because of underlying immunosuppression and frequent opportunistic lung infections. This condition. however, has been diagnosed uncommonly in these patients and, with the exception of one previously reported case. only in the presence of concurrent pulmonary infection. The case of a 35-year-old male with AIDS who was found on open lung biopsy to have pulmonary alveolar proteinosis without evidence of associated lung infection is presented.

Patients with acquired immunode ficiency syndrome (AIDS) are potential ly at increased ri sk fo r deve loping secondary pulmonary alveolar prote inosis because of underly ing immunosuppression and freq uent opportunistic lung infections .Thi s condit ion.howeve r, has been diagnosed uncommonly in these patients and, with the exception of one previously re ported case.only in the presence of concurrent pulmonary infection.T he case of a 35-year-old male with AIDS who wa s found on open lu ng biopsy to have pul monary alveolar protei nosis without e vidence of associ ated lung infect ion is presented.
P ULMONA RY ALV EOLA R PROTEINOS IS (PAP) IS AN UNCOM- mon condition that may be either primary (idiopathic).arising in an otherw ise heal thy pat ient, or secondary , where it occu rs in a setting o f a lte red immunity or conc urre nt lung infections.Patients with acqu ired immunodeficiency syndrome (AIDS) should be at risk for this disorder al-Proteinose alveolaire sans infection pulmonaire concomitante chez un patient sidatique RESUME : Les patie nts soutfrant du syndrome d'immunodefici ence acqu ise (SIDA) sont potentie llement a plus grand risque de deve lopper une proteinose alvcolaire secondaire [1 cause d 'une immunodeprcssion sous-jacente ct de frequentes in fections pul monaires opportuni stes.Cependant.cette affection a rarement ete diagnostiquee chez ccs patients et, ~1 !'e xception d 'un cas precedemmcnt rapporte\ scu lement en presence d ' une in fectio n pulrnonai re concom itante.Le cas d'u n ho rnme de 35 ans atteint du SIDA don! la biopsie pul rnonaire ouverte a revele une protei nosc alveolai re sans evi de nce d' une infection pul monaire concom itan te est presentc.
though it has rarely been repo11cd in this population (I).Previous reports of PAP in A IDS patients have usually been in the presence of an active or recent infection.We present a case without an as sociated lung infection which, to our kno wledge, has been re ported only once previously

CASE PRESENTATION
A 35 -ycar-old homosexual male was found to be pos itive !'or the hum an immunodeficiency virus (HIV) in 1987.He had documented P11c•11111ocystis rnri11ii pne umonia (PCP) in Ma rch 199 1 and again in April 1992.Because of ad verse effects from pentamidine and sulpha, he was maintained on Japsone as prophylax is against PCP.In addition, he had previously developed cutaneous Kaposi's sarcoma, whic h was treated with local irradiation.esophageal cand idiasis treated with rlucona1olc.and cutaneous herpes simplex inlection !'or which acyclovir was prescribed.fn July 1992.His symptom s and rad iog raphic ch anges persis ted un altered and in February 1993 an open biopsy o f the lingu la was perfonncd .Paraffin sections sho wed obl iteration of the dis tal airspaces by eos inophilic amorphous material which s tained variably pos iti ve with period ic acid-Schiff (PAS ) (Figure 3).No inflamm atory infiltrate, no specific viral changes and no inte rstitial process was seen.M ultip le sectio ns ex amined with Gomori's methenamine silve r (G MS) .Zieh l-Nee lse n, Fi te and Gram stains revea led no pathogenic organisms and an immunoperoxidase stain fo r cytomegalovirus (Chem icon, Cal ifornia) was negative.In addi tio n, routine c ul tures of the biopsy tissue fo r baeteria, viruses, fung i and mycobac te ria were negative.
No active treatme nt was inst ituted and at his foll ow-up two months later, he reported no new sy mptoms but was st ill dyspneic after walki ng one block.Six weeks later he was readm itted to hospital because o f increasing dyspnca, cough and hypoxemia.C hest radiograph revealed airspace disease in uppe r lung zones bilaterally.Bronchoscopy with BAL was un de rtaken and the results were di agnostic of PC P 011 this occasion.The patient initially improved with treatment and was discharged , but one week later required readmission due t(1 worsening dyspnea.rnugh and hypoxemia.Chest radiograph demonstrated more dense eonsolidation diffusely.His rnndition deteriorated rapidly and he suhsequently died./\n autopsy was not pL'rfonm:d.

DISCUSSION
PAP w,1s initially described in 1958 by Ros .. •n et al (3 ).Pathologil'ally. the characteristic change is an accumulation or amorphous PAS-positive phospholipids and proteins in the alveoli.with preservation of the interstitiurn.Various theories of its pathogenesis have been proposed that revolve around a disturbance of alveolar surfactant homeostasis.with a defect in the removal or resorption of surfactant being the most fo.rnured ( 4).The two classical symptoms are chronic cough.which is usually nonproductive.and progressive dy spnca on exertion.Less comnrnn symptoms include fever.weight loss.fatigue.chest pain and hemoptysis.Chest radiogra phs show nonspeci fic alveolar infiltrates without rncdiastinal lymphadenopathy.CT scans characteristically demonstrate a grey homoge neous appearance of the lungs related to the underlying consolidat ive process.Overlying thi s is a branching pattern of white linear structures representing the thickened interlobular septa between the secondary lobules.This results in an overall •crazy paving ' appearance typical of alveolar proteinosis (5).In contrast.PCP is a diffuse airspace disease that appears as focal areas of ground gl ass opacification on CT through which pulmonary vessels can still be identified.Kaposi •s sarcoma class ically takes on a nodular pattern in the pcrivascular and peribronchial regions (6).G:tllium scan is negative in PAP.Pulmonary function testing typically demonstrates a restrictive defect with decreased total lung capacity and vital capacity.along with a low diffusing capacity.The diagnosis nwy be made on BAL specimens due to the presence or granular acidophilic phospholipid material.which stains positively with PAS and has a characteristic nltrastructural appearance (7).
Transbronchial or open lung biopsy may be required rm diagnosis.Biopsy may also be required wlll'n the pos.~ibility of a concurrent process, particularly infection, remains in the differential diagnosis.PAS st::iining was not perfo1111ed on the BAL fluid in this patient because the diagnosis wa.~ not suspected.
Two forms of this pulmonary disorder have been described.with primary or classic P /\P occurring without an associated Gt use , while secondary P J\ P (oral vcolar phosplrnlipidosis) is reported to be linked to certain conditions.most imponantly lung infections (8 -10) and immunodeficiency stales ( 11 ).It seems that AIDS patients should he at risk for this latter form of PAP (I).HmVL'vcr.to our knuwlcdge, only nine cases of PAP have been reported in this patient popul::ition.in eight Llf whom it was as.~ociatcd with a simultaneous oppl>rtunistic lung infection.PCP was found in six cases (7).tuberculosis in one case ( 12). and PCP togcthn with dissemin;,itcd cytomegalovirus in one case ( 12).
The relationship between lung infcl'!ion and PAP in AIDS patients remains unclear.It is still poss ible that infection may have been an important part of the pathoge netic process in our patient.Although we were unable to demonst rate an associated infection.our patient did have previous PCP.which could have an un known pathogenetic role.or further concern is that our patient relied on a less effective agent.dapsone.as prophylaxis against PCP.Dapsone is used for both prirnary and secondary PCP prophylaxis.especially in tho •c who are intolerant of trimcthoprirn-sulfamethoxazolc.as was the case in our patient.Dapsone is felt to be as effective as aerosoli zed pcntamadinc, which is also used as prophylaxis against PCP and may he associated with a lower diagnostic yield for P carinii on BAL ( 13 ).but this issue h;,is not been studied with clapsone.Howe ver. the diagnostic gold standard is a lung biopsy and our patient did have transbronchial and open lung biopsies while he was on dapsone.hut neither dL•monstratccl P cari11ii or any other microorgani sms.To ensure this.\.VC carefull y examined approximately 8 cni2 of G MS stained tissue rrom several block• of the open lung biopsy and found no organi sms.We therefore believe that our patirnt is the second re ported case of PAP described in an AIDS patient without a concurrent or recent pulmonary infection.
Furthermore, superinfections ar .. • know n complications or PAP (4).Our patient was found lo have PCP 3 ..'i munths al'tl-r the diagnosis or PAP, with progressive deterioration until hi .s dem ise.Indeed.superimposed infections and rcspiratmy failure from the proteinosis arc the two major causes of dl'ath from this disorder.
In spite of a 30%, mortality from PAP noted bc!'orc the era of lung lavage .spontancou.s and uirnplctc remission is known to occur in 20 to 25 % of patients ( 14).l lowever.there arc no factors that acrnratcly 1m•dict which patient will suecumb.remit or respond to treatment.This unce11ainty in the natural course of PAP in any given patient serves to account for the lack of a specific and well-defined set of indicalinns for therapeutic intervention.V;1rious objective c riteria have been proposed.including arterial P0 2 less than 65 rnm Hg .differe nce in partial pressures or ox ygen in mixed alvl'olar gas and mixed arterial blood greater than 40 1111111 lg.shunt fractiun greater than IO to 12%.and all confirmed hi stologi cal diagnosis ( 15.16).Howe ver, the decision to reconm1L•nd treatment is generally based llll the extent to which PAP :1ffccts the patie nt in relation to his or her exe rcise tolerance , li fes tyle and occupation.That is.if the patient's dail y acti vities are limited by the symptums.treatment may be appropriate (4).
Various treatment options were usl'd in the past.including systemic cmticostcrnids and inhalation;d therapy with heparin.try ps in or acctylcysteine.hut they have largely been abandoned duL' to their side effects and lack or proven efficacy.Whole lung lavage is curently the therapy or choice and functions by mechanically removing the intra-alveolar phospholipids .11 is sal'c and effcctiVl' in the majmity of patients ii' pe11•ormed by an cxpcricncccl multidisciplinary team (4).However.sc.condary PAP. as seen with concurrent pulmunary infection and/or underlying imrnunodcl'iciency.may not have as favourable a response to whole lung lavage as pri-mm1 PAP.Therefore it may be important that the diagnosis of primary PAP not be made unless the po~sible secondary causes have been excluded because therapy may be best directed at these causes initially.T his underlies the need for histological examination of lung tissues in ce11ain cases to obtain an accurate diagnosis, thus allowing appropriate therapy to be given.