Persistent smear positivity for Mycobacterium tuberculosis in a patient with occult malignancy

Sir: The recent increase in prevalence of tuberculosis (T B) in North America anJ the emergence of multiple Jrug resis tant strains has stimulated renl:\Ved interest in the eharal:terization anJ treatment of TB. This resurgence in North America may be largely attributeJ to increased immigration from enul:mic areas. the emergence of human immunoJct'iciency virus (HIV) infection. inadequate living conditions and poor access to health care. However. the clinical course of the patient JcsnibeJ below serves as a reminder that TB need not be associated with these wiJcly appreciated risk fac tors. and careful investigation and follow-up may be necessary to reveal the cause of host immune defence impairment. The patient is a 56-year-old white male with a 25 pad.-ayear smoking history. He has a longstanding history of chronic cough productive of mueoiJ sputum con sistent with chronic bronchitis. The patient was referred for assessment after a six-month history of involuntary weight loss of uvcr 5 kg and an increase in mueopurulent sputum production. An incidental chest raJiograph (Figure I) demonstrated extensive diffuse nodular infiltrates in the left upper lung fielJ . associated with volume loss and pleural thickening. MoJeratc right upper lobe inriltratcs were also noted. A sputum stain was strongly positive llll both the acid fas t bac·illi (AFB) stain and direct fluorescent antiboJy (DFA) stain for mycubactcrium. Subsequent culture confirmed Mvcohucteriw11 111herc11/usis, which was sensitive to all the convcntillllal antitubcrculous agents. An HIV test was negative, and complete blooJ count and baseline liver function tests were normal. It was JctcrmincJ that the patient was born in Canada, with no significant travel history. and he was not lln any immunosuppressivc drugs. Other than the weight loss. there was no history of malignancy or Jiabctl:., mellitus. There was no other past medical history except for a moderate amount of alcohol consumption on a regular basis. His wife had TB IO years ago, for which she completed a successful course of anti tuberculous therapy . The patient did not receive isoniaLid prophylaxis and ht.' dcnicJ any history of T B. He was startL'U on a standard course of triple T B medications -· i.,oniazid 000 mg/day). rifompin (600 mg/clay) ,tnd pyrazinamiJe (25 mg/kg/clay) plus vitamin B6 (25 mg/day) . which he tolerated well. Compliance was ensured by bimonthly follow-up and dispensing of T B medications at three-month intervals plus regular home visits anJ survci !lance of pill supplies by a public health nurse. During the initial course of nine months of therapy he continued to smoke and consume a considerable amount or alcohol. However. he gaincJ weight. \vith noted improwmcnt in energy level and significant rL'duction in sputum


Sir:
The recent increase in prevalence of tuberculosis (T B) in North America anJ the emergence of multiple Jrug resis tant strains has stimulated renl:\Ved interest in the eharal:te rization anJ treatment of TB. This resurgence in North America may be largely attributeJ to increased immigration from enul:mic areas. the emergence of human immunoJct'iciency virus (HIV) infection. inadequate living conditions and poor access to health care. However. the clinical course of the patient JcsnibeJ below serves as a reminder that TB need not be associated with these wiJcly appreciated risk fac tors. and careful investigation and follow-up may be necessary to reveal the cause of host immune defence impairment.
The patient is a 56-year-old white male with a 25 pad.-ayear smoking history. He has a longstanding history of chronic cough productive of mueoiJ sputum con sistent with chronic bronchitis. The patient was referred for assess ment after a six-month history of involuntary weight loss of uvcr 5 kg and an increase in mueopurulent sputum production. An incidental chest raJiograph ( Figure I) demonstrated extensive diffuse nodular infiltrates in the left upper lung fielJ . associated with volume loss and pleural thickening. MoJeratc right upper lobe inriltratcs were also noted. A sputum stain was strongly positive llll both the acid fas t bac·illi (AFB ) stain and direct fluorescent antiboJy (DFA) stain for mycubactcrium. Subsequent culture confirmed Mvcohucteriw11 111herc11/usis, which was sensitive to all the convcntillllal antitubcrculous agents. An HIV test was negative, and complete blooJ count and baseline liver function tests were normal. It was JctcrmincJ that the patient was born in Canada, with no significant travel history. and he was not lln an y immunosuppressivc drugs. Other than the weight loss. there was no history of malignancy or Jiabctl:., mellitus. There was no other past medical history except for a moderate amount of alcohol consumption on a regular basis. His wife had T B IO years ago, for which she completed a successful course of anti tuberculous therapy . The patient did not receive isoniaLid prophylaxis and ht.' dcnicJ any history of T B.
He was startL'U on a standard course of triple T B medications -· i.,oniazid 000 mg/day). rifompin (600 mg/clay) ,tnd pyrazinamiJe (25 mg/kg/clay) plus vitamin B6 (25 mg/day) . which he tolerated well. Compliance was ensured by bimonthly follow-up and dispensing of T B medications at three-month intervals plus regular home visits anJ survci !lance of pill supplies by a public health nurse.
During the initial course of nine months of therapy he continued to smoke and consume a considerable amount or alcohol. However. he gaincJ weight. \vith noted improwmcnt in energy level and significant rL'duction in sput um productiun. Serial follmv -up cl1l'st radiographs revealed rnmplctL' clearing or his right lung ticld infilt rate and partial L'lcaring on the le!'t side with some residual 'scarring' . Serial sputum spec imens were consistently positive on AFB and DFA stains but extended 12-week cultures thro ug hout thcr-,tpy remained negati ve. Triple antitubercu lous therapy was maintained for a total of 27 months because or smear-posi tive sputum. Atypical mycobaeteriu m was never isolated in over 15 sputum cultures. The clinical susp icion or the prolongcJ spu tum smear positivity was host i111p,1irmcnt due to chnmic alcohol use.
Twent y-seven l\lllnths ,tlkr initiating antituherrnlous treatment . the patient de vel oped abdominal pain and ;rnorcxia. Subsequent investigations revealed a squamous cell carcinoma or thL' pancreas with hepatic metastases. AFB/DFA stains and mycobacterial cultures were negative on the pancreatic biopsy. The patient did not dewlop any other opportunistiL· infections.
This pat icnt was treated with sta ndarJ dosages of triple therapy for TB . Com pliance was satisfactory but despite a very prolonged course or bactericidal therape utic regi me n for T B. he failed to achi eve sputum conversion. The mycobacterial disease was clinically anJ radiologically controlled throughout the 27-month treatment interval. Despite the failure of sputum smear conversion. L·tilturcs WL' rL' consistently negativt: L'Vl'll llll 12-week extended culture s. No rcs istam·e strain was grown and no atypical mynihacteriu111 was grown on over I .' i cultures. Although no aprarent im mumisurrircssivc factors ,vere identified. the unusua[ clinical cour.,e was highly .,uggcst ive of impairment in the underlying host immune system. Ongoing smokin1:c with chronic hrnnchiti. , and alcohol nrnsumrtion arc likL'ly to have been imponanl adverse Lll'tors hut the occult malign,1ncy is pruhahly ,1 significant !'actor for immunological imrairme nl.
Although there have been only limited retrospective reviews of T B in malignancy. several studies have demonstrated an increased OCCLIITL'nce llf TB in the general population ( 1.2). T B is felt to he most prcvalt:nl in lymphom,1 and lung cancer (2) . although increased incidence has been described in other neoplasms.
Prolonged suppression of cell mediated immunity is a significant risk !actor for mycobactcrial in kct ion.,. ;\ long with patients with AI DS. cancer patients have significant impairment to their ccll mediatecl immunity. Thi s case serves as a reminder that care ful observation of patirnts with diffi-Can Respir J Vol 2 No 1 Spring 1995 Letter to the Editor rnlt tu eradicate Tl:3 with m> gross immunosuppressivc disease may in fact reveal occult immunosupprcssion due to underlying malignancy.