Tropical sprue in a case of heterosexually transmitted acquired immune deficiency syndrome

A heterosexual patient presented with severe diarrhea, malabsorption 
and weight loss. He was found to have acquired immune deficiency syndrome 
(AIDS) on the basis of candida esophagitis. Pneumocysris carinii pneumonia, inversion 
of T lymphocyte subpopulation ratio and the presence of serum anti-HIV virus 
antibodies. The patient had travelled to Haiti and the Dominican Republic where he 
had multiple sexual contacts with indigenous women. Despite thorough evaluation 
to identify the cause of diarrhea no infection, agent was discovered. Duodenal biopsy 
showed partial villous atrophy, slight crypt hyperplasia and increased number of 
intraepithelial lymphocytes. After two weeks treatment with tetracycline and folic 
acid. the patient was symptom free and intestinal histology had returned ro normal. 
Tropical sprue must thus be considered in the differential diagnosis of intestinal 
villous atrophy in patients with AIDS.

acqu ired immune deficiency syndrome (A IDS), there have been many reports of infectious, in fl ammatory and 1umoral involvemen t of the gastroi n testinal tract in association with this disease (1•4).Indeed, diarrhea and weigh t loss are common complain ts among A IDS patients and can at times be the predominant clinical problem.Wh ile in certain of these subjects specific infectious agents can be found (2,3), in others, no infec-tious e tiology can be ascertained despite extensive clinical and microbiological investigation.ln the latter grou p, jejuna!and colorectal abnormalities h ave been reported ( 5.6).Of the jejuna!abnormalities described , one has been termed pseudo-Whipple's disease in that mucosa I biopsies dem0 n strate abun d ant foamy macrophages.T his enti ty is though t to resu lt from gastrointestinal in volvement i.n a systemic Mycobacterium ,wi1tm infection (7).A second type of jejuna[ involvemen t, in th is cnse of unknown etiology, results in a partial villous atrophy associated with crypt hyperplasia and increased number of intraepithelial lymphocytes 15 ).Although th is h istology cou ld suggest the diagnosis of sprue, n eith er a gluten-free diet nor an tibiotic treatment hns resulted in clinical or h istological re-missi0n of the jejuna!anomaly or of th e consequent d iarrhea and malabsorption (5.8).
A case of a patient with documented AIDS, who pre:,ented such a histological jejuna!abnormality with an associated malabsorption is reported.Because he had been travell ing man area where tropical sprue is known to be e ndemic and as there is no known treatment for A IDS-related e n teropathy, a treatmen t known to give good results in tropical sprue was attempted.

CASE PRESEN TATION
A 41-year-old, white, French Canadian.excl usively heterosexual male, was in good health , except for moderate obesity (95 kg) u n til March 1985 when he developed nonbloody d iarrhea with a stool frequency of eight to 12 bowel movements per day.At that time, he had recently re tu rned from a rwo-month vacation to the Dominican Republic and Haiti wh..:-rc he had been travelling on regular occasions for the past five years.While abroad he had hnd multiple sexual contacts with indigenous women He was asymptomatic during and after previous trips only to develop diarrhea within two weeks of his last return.
When the patit:-nt first presented at the emergency ward he was dehydrnted, had lost 4 to 5 kg and had slight hypokalcmic acidosis.At that tune, stool cultures revealed the presence of Cam/rylobacier fetus subspecies 1ejun1.With this data at hand. it was decided to obtain directly a small bowel mucosa!biopsy through the gasrroJuodenoscope.Upper gastroin tesrinal endoscopy revealed multiple white, spotty exudates lining the entire esophageal wall, brushings and biopsies of which showed the presence of Candida alb1cans and an associated esophagitis.Concurrent distal duodenal mucosa!biopsies revealed subrotal villous atrophy with slight crypt hyperplasia and increased intracpithclial lymphocytes (Figure J) No G1cmlia nr Cry/)losporidia were seen on the epithelial surface.Rectal biopsy was normal Subsequent complemenwry investigations revealed a blm1d carntencrnia at (1 mg/ WO m L. folk acid at 1.11 mg/ 100 ml ( normal I 7 to J 5. 5) with a normal B 11 ,ind a 2 h blcxid n-xylosc t,f 6 mg/ IOL1 ml ( normal, more than 2 5 ).Transhronchial lung biopsy showed numerous Pne1-t1noc-y~1is carm11.Serology gave ;1 negative VDRL and HBsAg anugen whcrcas antibodies to HIV virus were positive T helper lymplwcytcs were 391 cells/ mm 1 , T suppre~sor lymphoc ytes H5,f cells/mm I and T helper to T supp1-css(1r ratio was deprc•ssed at \1 45 The patient was treated with intrnve• nous trimerhopnm-su lfamcthoxasole for rhe Pneumocys1iscarin11 penumon1a and with kctocona:olc for the candida e:.ophagitis.He responded well to both 1rea1-me1w,.A:, for the diarrhea, with subtmal duodem1l atrophy, 11 was hypothesized that he may have acqwred tropical :,pruc during his travels w a known endl'mir area ,rnd was therefore treated with I he combination of tetracycl111c and folic acid.He responded very well to th is therapy and bec,1me asympwmauc within 10 days.Subsequent distnl duodenal mucosa!biopsy repeated 20 days after the bt'ginning of the treatment ,hO\wd an almost complett' reversal of rhe duodenal v1 llous mrophy (Figure 2 ).
The patient was suhsequcntly dis- charged from hospnal and followed as an outpatient Six monchs later, he had regained the 30 kg which he had lost during his il lness and remai ned perfectly healthy taking no medication A t this ume, his T helper to T suppressor ratio remained depressed at O 4, and he remained aneqpc to common antigens.At cndoscopv, to obtain a control intestinal biopsy, he was found to have several ,mall wh ite plaqu~•s in the esophagus which were shown 10 be Candida alb1camon cytological smears.Intesti nal biopsy taken at the same endoscopic ses-,ion showed normal duodenal histology 1F1gure 2).D-xylose absorpuon had also returned to normal.Although asymptomauc he was given a two week course of oral nyscatin.Two months lacer he remained well and without symptoms.
Fifteen months afrer h is original pre--cntation he developed cyclic fever followed by headaches of progressive intensity.He had no gas t rointest i nal ,ymptoms.Appropriate mwscigauons revealed cerebral toxop lasmosis for which he was treated with pyrimethamine a nd su lfamethoxasolc.He suc-(Umbed co this opportunistic mfccnon two months later without recu rrence of the gamointestinal problems.

DISCUSSION
The association of nn acq u ired defect m cellu lar immunity, de monstrated by mabsolute lymphopenia ( 1070 lympho-\'olZ o2.June1988 cyces/mm 1 ) sclecnve for OKT~ helper/ inducer lymphocytes, 11•1th che documentation of three opponuni~cic infccuons including Pneumocym1 cann11 pneumonia, CanJiJa alh1ca111 esophag1us and cerebral toxoplasmos1s, meets the Centre for Disease Control cncena for the J1ngnosis of A IDS.The d iagnosb li( A IDS in this case was further supported by the presence of a definite risk factor m that the patient had multiple heterosexual relat1ons with Hai11nns in whom the prevalence of H IV infections seems morJinaccly elevated (9, 10).Furthermore ihe prcsencco(H!Vancibodiei;confirms previous contact with huma n T cell lymphotropic retrovirus thought to be che mfeccious agent responsible for th is d isease ( l l ).A second important criteria 1n the Centre for Dhcase Control's defirntion of AIDS specifics that no other idenufiahle cause can be found for the underlying immunodeficiency ( 12).
In the presen t case, the patient presented with severe 111test1nal malabsorpcion with the resulting p rotein-caloric malnutrition wh ich produced a loss of 30'\, of hb original body weigh t.Such protein-calone malnutrition is known to ind uce immunodeficiency states.Indeed, decreased coral T lymphocyte counts, T helper and suppressor counts and lgA secretion have been described m such states of malnutrition ( 1 ,).Protem-calone malnutrition has also hcen thought to be an important factor 111 epidemics of Pn~11mocy1t1.1 carin,i pneumonia in malnourished children ( 14 ).In this case, the role of the malahsorption.with its con-Sl'quent immunodeficiency, on till' op-portunbt1c 111lccc10ns sustained hy che patient can only be speculated.Superimposition of Sl'vere malahsorpnon may have turther depressed his immune systl'm and rendl'rl'd h,m more susceptihk to (1pponunist1c mfccuons The duodenal v1llous atrophy wnh concurrent nu trient malahsorption observed is by no means specific and diagnostic of tropical sprue.Several in fectious and nonrnfcctious e n teropathics could very well have given the ~ame clinical and h istological picture.Of the intestinal infections known to produce similar vi llous patterns, both giard im,is and cryptosporidios1s were excluded by the study of multiple stool specimens and endoscopic duodenal a~pirates looking specific.illyfor these pnrhogens.Furthermore, intestinal biopsy showed no evidence of parasites aJhering to the cnterocytes.Systemic Mycobact(.•mimlll•ium infection can be excluded on chc has1s of h istology as this infection h ns been shown to produce a hiscolog1cal picture resembling Wh ipple\ disease with an accumulation of hist1ocytes m che lamina propna.The difference from Whipple's disease, however, is that these hist1ocytes contain numerous acid-fast rods (7 ).The AIDS-related cnteropathy, for which there 1s yet no etiology and which gives a histological p icture undifferentiablc from rhat observed in th is patient (5), docs not respon d to tetracycline treatment (5,8).However, tetracycline and folic acid the rapy resu lted in a rapid resolution of the jejuna! in flam matory process in the case described here.
The response observed followi n g antibiotic treatment could also suggest the possibility of the syndrome of matabsorption resulting from intesti nal bacterial overgrowth associated with a b li nd loop or an intestinal motor abnormality.T he present patient had had no previous gastrointestina l surgery.had normal gastrrnntcstinal rocntgcnograms, apart from slight dilatation of the proximal jeju num, and had no systemic d isca~e known to alter intestinal motil ity wh ich mitigates against lt'lt~ po:;s101lny.rurchermore,although decreases in intesti nal secretory lgA have been shown co occur in A IDS patients ( 15), bacterial overgrowth has yet to be reported as a cause of malab-sorption in these patients.Decreases in serum folic acid is also qu ite u n usu al in such cases of bacterial overgrowth ( 16).
On the contrary, serum folic acid is usually normal and may even be elevated as a result of a folare production, by th e bac• cerial flora, wh ich may surpass the degree of bacterial folace utilization an d m ucosa!malabsorpcion (17).
A lthough tropical sprue is also thought co be the resu le of a form of bacterial overgrowth , che intestinal flora responsible for th is lesion seem different from that encountered in the blind loop syndrome.

FigureFigure 2 )
Figure I ) EnJom,pic duoJe,wl h10J1,y taken ,11 original /1rescnlluion Left Subroral 1111/01~1 arrophy wirh broadening of l'lllr anJ 111/i/mmom tMh c/mmtt mflarnmarory cells ( H PS X 70) R ight Surface eptrhdium wtrlt low columnar anJ C11l101dal cJ1irhelial cdh wi1h rhe msociared m/lammawry m{iltnuc>I HI'S X JlX)/ Alth ough therapy with tetracycli ne is generally ineffective in the treatment of AIDS-re laced en teropathy, patien ts p resen ting with this clinical and histological picture who report a history of recen t travel to areas of th e world wnerc uop1ca1 5prue 1~ cnal!m1c ma\ benefit from such a treatment.lr may be more important co con sider ch is possibility in Haitians with ArDS and jejuna!vi llous atrophy.