We report a 38-year-old Chinese woman with lupus nephritis on peritoneal dialysis and long-term maintenance steroid therapy. This patient developed paradoxical deterioration during anti-tubercular therapy for tuberculous lymphadenitis. The deterioration resolved spontaneously without change to pharmacotherapy. Paradoxical deterioration that may spontaneously resolve is a potential complication of anti-tubercular treatment in patients on long-term renal replacement therapy.published_or_final_versio

Cheng, VCC

Hung, IFN

Lo, WK

Lui, SL

Hong Kong Medical Journal

HKU Scholars Hub

Title Paradoxical deterioration during anti-tubercular treatment in adialysis patient on maintenance steroid therapyAuthor(s) Hung, IFN; Cheng, VCC; Lo, WK; Lui, SLCitation Hong Kong Medical Journal, 2005, v. 11 n. 3, p. 210-212Issued Date 2005URL http://hdl.handle.net/10722/77321Rights Hong Kong Medical Journal. Copyright © Hong Kong MedicalAssociation.210      Hong Kong Med J Vol 11 No 3 June 2005CASE REPORTKey words:Antitubercular agents;Peritoneal dialysis;Steroids;Tuberculosis ! !"# !" ! Hong Kong Med J 2005;11:210-2Paradoxical deterioration duringanti-tubercular treatment in adialysis patient on maintenancesteroid therapy○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ !"#$%&'()*+,-./0()12 !"#$Division of Nephrology, Department ofMedicine, Tung Wah Hospital,Hong KongIFN Hung, MB, BS, MRCPWK Lo, FRCP, FHKAM (Medicine)SL Lui, MD, FRCPDivision of Infectious Diseases, Centre ofInfection, Queen Mary Hospital,Hong KongVCC Cheng, MB, BS, MRCPCorrespondence to: Dr SL Lui(e-mail: sllui@hku.hk)IFN Hung  VCC Cheng  WK Lo  SL Lui  We report a 38-year-old Chinese woman with lupus nephritis onperitoneal dialysis and long-term maintenance steroid therapy. Thispatient developed paradoxical deterioration during anti-tuberculartherapy for tuberculous lymphadenitis. The deterioration resolvedspontaneously without change to pharmacotherapy. Paradoxicaldeterioration that may spontaneously resolve is a potential compli-cation of anti-tubercular treatment in patients on long-term renalreplacement therapy. !"#$PU !"#$%&'(")*+,-./01234 !"#$%&'()*+,-./0,12345,-%&678 !"#$%&'()*+,-.!/0 !1234$%&56 !"#$%&'()*+"#,'-./01%234567 !"#$%&'(IntroductionParadoxical deterioration during anti-tubercular therapy refers to theclinical or radiological worsening of pre-existing tuberculous lesions orthe development of new lesions not attributable to the normal course ofdisease in a patient who initially improves with anti-tubercular therapy.1This phenomenon is more commonly associated with extrapulmonarytuberculosis.2 There is no specific diagnostic test for such paradoxicaldeterioration, although a surge in lymphocyte count is suggestive of sucha diagnosis.2,3 Paradoxical worsening during treatment for tuberculosishas been extensively reported in AIDS patients, particularly followingtherapy with highly active antiretroviral agents.3-5 It is also well recog-nised in patients without HIV infection.1,2,6-8Patients with chronic renal failure are more prone to opportunisticinfections, including tuberculosis.9-11 In patients undergoing continuousambulatory peritoneal dialysis (CAPD), the prevalence of tuberculosis isseveral times higher than that of the general population.10 Nonetheless, aparadoxical response during anti-tubercular therapy has not been reportedin such patients and has not, apparently, been previously described inpatients receiving long-term steroid therapy. We report a patient withunderlying lupus nephritis on CAPD and maintenance steroid therapywho demonstrated a paradoxical deterioration during treatment fortuberculous lymphadenitis.Hong Kong Med J Vol 11 No 3 June 2005      211Paradoxical deterioration during anti-tubercular treatmentCase reportThe patient was a 38-year-old Chinese woman withend-stage renal failure secondary to lupus nephritis whocommenced haemodialysis in 1995. In March 2002,she switched to CAPD because of failed vascularaccess. A history of cerebral lupus was noted forwhich long-term maintenance steroid therapy wasprescribed (prednisolone 5 mg daily). Lupus activityhad been clinically and serologically inactive follow-ing commencement of renal replacement therapy.In September 2002, the patient presented withfever and appearance of a left upper neck swelling.Physical examination revealed enlarged left uppercervical lymph nodes. No other lymph nodes wereaffected, nor were the liver or spleen. Preliminaryinvestigations revealed the following: normal totalwhite cell count (4.4 x 109 /L) with relative lympho-penia (0.6 x 109 /L), haemoglobin level of 67 g/L, andplatelet count of 90 x 109 /L. Erythrocyte sedimenta-tion rate was 32 mm/h and C-reactive protein waselevated at 34.4 mg/L (reference level, <7.6 mg/L).Serum electrolytes and liver function tests were un-remarkable. Serum albumin and globulin levels were23 g/L and 40 g/L, respectively. Her lupus serologywas quiescent: antinuclear factor titre 1/160, anti-DNAtitre less than 1 IU/mL (reference range, 0-35 IU/mL),complement levels normal (C3, 1140 mg/L [referencerange, 760-1500 mg/L]; C4, 300 mg/L [referencerange, 90-350 mg/L]). She was seronegative for HIV.Chest radiography revealed clear lung fields and nasalendoscopy was normal. Fine needle aspiration of theleft cervical lymph node yielded several millilitres ofpus-like material. Smear examination and culture ofthe aspirate was negative for bacteria and acid-fastbacilli. Cytology was negative. Excisional biopsy ofthe cervical lymph node revealed granuloma formation,extensive caseous necrosis, and the presence of acid-fast bacilli by Ziehl-Neelsen stain. A diagnosis oftuberculous lymphadenitis was made and the patientwas given supervised anti-tubercular therapy (dailydoses of isoniazid 200 mg, rifampicin 450 mg, pyrazi-namide 1.5 g, levofloxacin 200 mg, and pyridoxine100 mg). Cultures of the aspirate and excisionalbiopsy from the left cervical lymph node subsequentlyyielded Mycobacterium tuberculosis that wassensitive to standard anti-tubercular drugs. The patientwas maintained on the existing 5 mg per day oralprednisolone. The enlarged cervical lymph nodesdecreased in size after the initiation of anti-tuberculartherapy, but increased again along with tender rightaxillary lymphadenopathy 2 weeks later. Total whitecell count at the time was normal but lymphocytecount had increased to 1.4 x 109 /L. Fine needle aspi-ration of the right axillary lymph node revealed acid-fast bacilli on smear, although subsequent bacterialculture was negative. Lupus serology remained stableand a provisional diagnosis was made of paradoxicaldeterioration. Anti-tubercular and steroid therapy wascontinued. Cervical and right axillary lymph nodesdecreased in size after a week and completely resolved3 weeks later, and the patient’s general conditiongradually improved. Anti-tubercular drug therapy wascompleted uneventfully and maintenance steroidtherapy continued.DiscussionWe report a lupus patient on CAPD and maintenancesteroid therapy who developed paradoxical deteriora-tion during treatment for tuberculous lymphadenitis.The paradoxical deterioration resolved spontaneouslywith continuation of anti-tubercular drugs and with nochange in steroid dosage.Paradoxical deterioration during anti-tuberculartreatment is diagnosed by exclusion. Enlargement ofcervical lymph nodes and appearance of new enlargedlymph nodes in the axilla after initial improvement onanti-tubercular therapy suggests a number of differen-tial diagnoses: inadequate anti-tubercular treatmentdue to drug resistance or poor drug compliance, con-comitant bacterial infection, and, rarely, re-activationof lupus activity.12 Nonetheless, supervision of anti-tubercular therapy together with biochemical andmicrobiological testing excluded them all. Thedemonstration of acid-fast bacilli on direct smear butnot from culture of the patient’s axillary lymph nodeaspirate indicated that the acid-fast bacilli were notviable after 2 weeks of anti-tubercular treatment. This,together with the spontaneous resolution of lymph-adenopathy while continuing anti-tubercular treatment,suggested a diagnosis of paradoxical deterioration. Thesurge in lymphocyte count during the time of apparentclinical deterioration further supported this diagnosis.Paradoxical deterioration during anti-tuberculartreatment is not uncommon. The prevalence of para-doxical deterioration among HIV-negative patientsduring treatment for tuberculosis has been recentlyreported at 11.1%.2 Tuberculosis is also commonamong patients with chronic renal insufficiency,9-11 butparadoxical deterioration has not previously beenreported. It is possible that patients on dialysis areless prone to develop paradoxical responses: the hostimmune responses of such patients are altered andthere is a high rate of anergy.13-15Hung et al212      Hong Kong Med J Vol 11 No 3 June 2005The pathogenesis of paradoxical deteriorationduring anti-tubercular treatment remains to be fullyelucidated. It may be related to the development ofenhanced immunological responses against Mtuberculosis during the course of anti-tuberculartherapy.16,17 In HIV-infected patients who developparadoxical deterioration during anti-tubercular treat-ment after having received highly active antiretroviraltherapy, clinical deterioration may be due to the im-mune reconstitution inflammatory syndrome, an exu-berant inflammatory response towards the incubatingMycobacterium.18 Corticosteroids have been prescribedto treat paradoxical deterioration.7 Interestingly thisoffered no protection for the patient reported here.The dose was nonetheless small and might have beeninsufficient to entirely suppress the inflammatoryresponse. The concomitant administration of isoniazidmight also have reduced the effectiveness of the steroid.There is no consensus on the optimal treatment forparadoxical deterioration during anti-tuberculartreatment. The condition may be self-limiting asdemonstrated by our patient. An expectant approachis probably called for with the continuation of anti-tubercular and pre-existing steroid therapy. Such anapproach will also avoid the problem of side-effectsassociated with high-dose steroid therapy.Paradoxical deterioration during anti-tuberculartreatment can occur in CAPD patients on maintenancesteroid therapy. Although self-limiting, cliniciansshould recognise this potential complication. In theabsence of other causes of clinical deterioration, spon-taneous resolution can be expected with no changerequired to any anti-tubercular or other concomitantpharmacotherapy.References1. Cheng VC, Ho PL, Lee RA, et al. Clinical spectrum ofparadoxical deterioration during antituberculosis therapyin non-HIV-infected patients. Eur J Clin Microbiol InfectDis 2002;21:803-9.2. Cheng VC, Yam WC, Woo PC, et al. Risk factors fordevelopment of paradoxical response during antituberculosistherapy in HIV-negative patients. Eur J Clin Microbiol InfectDis 2003;22:597-602.3. Orlovic D, Smego RA Jr. Paradoxical tuberculous reactionsin HIV-infected patients. Int J Tuberc Lung Dis 2001;5:370-5.4. Chien JW, Johnson JL. Paradoxical reactions in HIV andpulmonary TB. Chest 1998;114:933-6.5. Narita M, Ashkin D, Hollender ES, Pitchenik AE. Paradoxicalworsening of tuberculosis following antiretroviral therapyin patients with AIDS. Am J Respir Crit Care Med 1998;158:157-61.6. Afghani B, Lieberman JM. Paradoxical enlargement ordevelopment of intracranial tuberculomas during therapy:case report and review. Clin Infect Dis 1994;19:1092-9.7. Bukharie H. Paradoxical response to anti-tuberculousdrugs: resolution with corticosteroid therapy. Scand J InfectDis 2000;32:96-7.8. Janmeja AK, Das SK. Cervico-mediastinal lymphadenopathyas a paradoxical response to chemotherapy in pulmonarytuberculosis. A case report. Respiration 2003;70:219-20.9. Hussein MM, Mooij JM, Roujouleh H. Tuberculosis andchronic renal disease. Semin Dial 2003;16:38-44.10. Lui SL, Tang S, Li FK, et al. Tuberculosis infection inChinese patients undergoing continuous ambulatoryperitoneal dialysis. Am J Kidney Dis 2001;38:1055-60.11. Taskapan H, Utas C, Oymak FS, Gülmez I, Özesmi M. Theoutcome of tuberculosis in patients on chronic hemodialysis.Clin Nephrol 2000;54:134-7.12. Lui SL, Lam MF, Tse KC, Lo WK. Reactivation of systemiclupus erythematosus in a dialysis patient after tuberculousperitonitis. Lupus 2002;11:49-51.13. Goldblum SE, Reed WP. Host defenses and immunologicalterations associated with chronic hemodialysis. Ann InternMed 1980;93:597-613.14. Smirnoff M, Patt C, Seckler B, Adler JJ. Tuberculin andanergy skin testing of patients receiving long-termhemodialysis. Chest 1998;113:25-7.15. Woeltje KF, Mathew A, Rothstein M, Seiler S, Fraser VJ.Tuberculosis infection and anergy in hemodialysis patients.Am J Kidney Dis 1998;31:848-52.16. Ellner JJ, Wallis RS. Immunologic aspects of mycobacterialinfections. Rev Infect Dis 1989;11(Suppl 2):455S-459S.17. van Bommel EF, Stiegelis WF, Schermers HP. Para-doxical response of intracranial tuberculomas duringchemotherapy: an immunologic phenomenon? Neth J Med1991;38:126-30.18. Shelburne SA 3rd, Hamill RJ. The immune reconstitutioninflammatory syndrome. AIDS Rev 2003;5:67-79.

Paradoxical deterioration during anti-tubercular treatment in a dialysis patient on maintenance steroid therapy

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Paradoxical deterioration during anti-tubercular treatment in a dialysis patient on maintenance steroid therapy

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