Case Reports of Malignancy Associated With Infliximab
A search of available published literature from
In total, 23 case reports of malignancy with
infliximab exposure have been identified. Of these 23 malignancies,
3 patients received infliximab for ankylosing spondylitis; 10 patients
for Crohn’s disease (CD); 1 patient for psoriasis; 6 patients
for rheumatoid arthritis , including 1 patient that had overlapping
CD; and 3 for ulcerative colitis. Two patients were treated for another
immune-mediated condition. Of the 23 patients with a reported malignancy,
16 patients were diagnosed with a malignancy while being treated with
infliximab therapy, 4 patients had been previously treated with infliximab;
the time from last infusion of infliximab was not reported in 3 cases.
Infliximab therapy was discontinued in the patients being treated
at the time of malignant diagnosis. Malignancy outcome data were reported
for 15 (of 23) of these patients. Of the 15 patients with outcome
data, there were 3 fatalities in CD patients treated with infliximab
(1 case of cutaneous
Additional cases of malignancy have been reported in published retrospective studies summarized in the section, Infliximab and Malignancy: Other Published Literature. Further, cases of hepatosplenic T-cell lymphoma have been summarized in a table found in Hepatosplenic T-Cell Lymphoma and Infliximab.
| Age When Malignancy Diagnosed Sex Publication | Malignancy Information | Disease State (AS, CD, PsA, PSO, RA UC) and Duration | Dose(s) of Infliximab Regimen | Time From Last Infliximab Dose to Malignancy | Other Immuno- suppressant Medication History | Outcome(s) |
|---|---|---|---|---|---|---|
|
72-y-old Male El Mansouri 200912527 |
Invasive ductal carcinoma of the breast;
localized; hormone receptor positive, Family history of breast cancer |
AS |
Infliximab therapy for 2 years Dose and regimen not specified |
Receiving treatment at time of diagnosis |
Treatments prior to infliximab therapy included: Etanercept (2 y) |
Patient underwent total mastectomy with axillary LN excision. No evidence of metastatic spread Patient received local radiation therapy and antiestrogen hormone therapy. |
|
32-y-old Male Sanli 200711407 |
Mycosis fungoides; no extra cutaneous involvement, EBV DNA negative |
AS |
Mainten- ance at |
Receiving treatment at time of diagnosis |
Treatments prior to infliximab therapy included: Sulfasalazine |
Infliximab therapy was discontinued. Lesions were stable for 2 months, patient then began PUVA therapy. |
|
75-y-old Male Dauendorffer 200711408 |
Sézary’s syndrome |
AS (duration not specified) with diffuse erythe- matous and squamous plaques |
17 consecu- tive infusions every |
Receiving treatment at time of diagnosis |
Treatment after discontinuation of infliximab therapy: MTX |
Infliximab therapy was discontinued. MTX Reported regression of most cutaneous lesions |
|
25-y-old Male Murakami 200912528 |
Hepato- cellular carcinoma (localized) No metastases were seen. |
CD (12 y) |
|
Receiving treatment at time of diagnosis |
Treatments prior to infliximab therapy included: Prednisolone and AZA (doses unspecified) |
Infliximab therapy was discontinued. Patient underwent right hepatic lobectomy. No recurrence of tumor |
|
21-y-old Male Outlaw 200912529 |
Lyphomatoid Papulosis, a rare cutaneous T-cell lymphoma |
Fistulizing CD (13 y) |
Infliximab therapy for Dose and regimen not specified |
Receiving treatment at time of diagnosis |
Concomitant AZA |
Biopsy of scattered bluish-purple popular nodules (rash) on extremities and buttocks consistent with lymphomatoid papulosis Infliximab therapy was discontinued. Rash resolved in a few months; remains in remission
at |
|
39-yr-old Male Melichar 200912536 |
Mucinous anorectal adenocarci- noma; Stage II (no lymph node involvement); partially associated with a fistula; tumor classification was T3 |
CD |
5 mg/kg at Wk 1, 2, and 6 Approximately 5 mo later, patient received additional course of infliximab |
Approximately 2-3 months |
Treatment prior to infliximab therapy included: Mesalazine Concomitant mesalazine and budesonide |
Infliximab therapy was discontinued. Patient underwent radical resection. Adjuvant radiotherapy and chemotherapy were initially deferred. Patient experienced recurrent metastatic carcinoma 5 months after initial diagnosis. Patient failed multiple anti-neoplastic therapies. Patient experienced an exacerbation of CD and progressive malignant disease. Patient
refused further anti-neoplastic therapy and died |
|
35-y-old Male Bai 200912537 |
Rectal EBV-positive HL; prior to CD diagnosis, patient was diagnosed and successfully treated for small-bowel adenocarci-noma (T4, N1, M0) |
CD (7 y) |
2 doses of infliximab |
Receiving treatment at time of diagnosis |
Treatments prior to infliximab included: Metronidazole |
Infliximab therapy was discontinued. Patient underwent oncologic follow-up and antineoplastic chemotherapy. At 8-mo follow-up, there was no evidence of local progression or secondary lesions. |
|
71-y-old Female Podolsky 200912538 |
Diffuse large B-cell lymphoma |
CD (49 y) |
Dose not specified infusion every 8 wk for 3 y |
Receiving treatment at time of diagnosis; last dose 4 wk prior to diagnosis |
Treatment prior to infliximab included: Prednisone |
CT scan revealed heterogeneous mass in the right side of the thalamus. Patient had seizure and became unresponsive. |
|
34-y-old Female Zagoni 200912530 |
Metastatic, mucinous adenocarci- noma |
Fistulizing CD (14 y) |
Dose and regimen not specified Two doses at 7 and 2 mo prior to malignant diagnosis |
2 mo prior to malignant diagnosis |
Treatment prior to infliximab therapy include: 5-ASA, azathioprine |
Patient received palliative treatment but expired 10 mo after diagnosis. |
|
46-y-old Male Zágoni 200612530 |
Adenocarci- noma (associated with fistula, moderately differentiated) |
Fistulizing CD (28 y) |
2 infusions (dose and regimen not specified) |
Receiving treatment at time of diagnosis |
Treatments prior to infliximab therapy included: Metronidazole and AZA |
At time of publication, patient was receiving anti-neoplastic therapy. |
|
79-y-old Female Smith 20088056 |
Invasive perianal adenocarci-noma |
Perianal CD |
Dose, regimen, and duration of infliximab therapy not specified |
Not reported |
Treatments prior to infliximab included: Sulfasalazine |
Patient underwent abdomino- perineal resection and radical vulvec-tomy No further treatment was specified |
|
45-y-old Male Dossett 20078055 |
Invasive small bowel adenocarci-noma of the terminal ileum; stage II |
CD |
Dose not specified 5 infusions for acute exacerba- tions |
Not reported |
Treatments prior to infliximab therapy included: Steroids and AZA |
Patient underwent partial resection of the ileum and cecum. Patient did not receive adjuvant anti- neoplastic therapy.
|
|
81-y-old Female Adams 200411575 |
Cutaneous |
CD (exact duration of disease not specified) |
Dosage not specified 3 infusions over |
|
Not reported |
MTX therapy was initiated with improvement in cutaneous lesions. Patient died |
|
50-y-old Male Girard 200811668 |
Gastric MALT lymphoma |
PsO |
|
Receiving treatment at time of diagnosis |
Treatment prior to infliximab included: Conventional therapies, other |
Infliximab therapy was discontinued; replaced
with MTX Patient
was treated for MALT by eradication of
Reported residual disease at time of publication |
|
70-y-old Male Khan 200912531 |
Melanoma of the scalp |
RA (9 y) |
|
Receiving treatments when pigmented lesion developed (after 1 y treatment) |
Concomitant MTX (12.5 mg once weekly for 5 y) |
Patient underwent wide local excision. No metastasis to LN Infliximab therapy was discontinued. |
|
53-y-old Female Jaworski 200912532 |
Malignant melanoma of the skin |
RA (15 y) |
3 mg/kg induction at Weeks 0, 2, 6 Maintenance every 8 wk |
Receiving treatment at time of diagnosis |
Treatments prior to infliximab therapy included: Salazopyrin |
Infliximab therapy was discontinued Patient underwent radical resection with no adjuvant antineoplastic therapy |
|
62-y-old Female Lourari 200912539 |
Mycosis fungoides (cutaneous T cell lymphoma); EBV negative |
RA (23 y) |
Dose and regimen not specified 16 infusions over 29 mo |
Receiving treatment at time of diagnosis |
Concomitant MTX during 12 mo prior to malignant diagnosis |
Infliximab therapy was discontinued. Patient experienced spontaneous regression of skin lesions within wk; at 15 mo follow-up, no residual malignant disease |
|
64-y-old Female Thonhofer 2009 12602 |
Extranodal marginal zone B cell lymphoma of the MALT type |
RA |
Dose and regimen not specified 15 infusions |
Receiving treatment at time of diagnosis |
Concomitant MTX-sulfasalzine treatment |
DMARD therapy discontinued Infliximab therapy discontinued No evidence of lymphoma infiltration into bone marrow. MRI and CT scans were unremarkable. Biopsy of stomach revealed H. pylori infection, which was treated. Anti-neoplastic therapy was not initiated. Repeat MRI of head and neck at 3 and 6 mo showed no evidence of tumor. Patient was in clinical remission at time of publication. |
|
53-yr-old Female Nakashima 200711671 |
|
RA (28 y), CD (5 y) and other non- indicated
use |
|
Receiving treatment at time of diagnosis |
Concomitant MTX (dose not specified) for 52 mo |
MTX and infliximab therapy were discontinued. Anti-neoplastic therapy resulted in tumor reduction. |
|
59-y-old Female Pimenta 20078057 |
Squamous cell carci-noma of the skin |
Refractory RA (long-term, duration not further- specified) and rectocolitis |
Regimen not specified |
Not reported |
Treatments prior to infliximab included: A combination of cyclosporine |
Not reported |
|
45-y-old Female Lopez San Roman 200811669 |
EBV- associated large |
UC |
3 infusions at Wk 0, 2, and 6 |
Infused until diagnosis (2 mo after infliximab initiation) |
Treatments prior to infliximab therapy included: Oral prednisone |
Immunosup-pressants were discontinued Patient underwent proctocolec-tomy. No signs of lymphoma relapse |
|
69-y-old Female Lees 200811670 |
|
UC |
Episodic treatment over |
|
MTX (2003 to time of publication, dose not specified) Treatment subsequent to infliximab: Other |
Complete clinical and radiologic remission without anti- neoplastic therapy |
|
9-yr-old Male Yildrim- Toruner 200811666 |
HL; nodular sclerosis subtype, stage IV B |
OTH |
Every 6 wk over 3.5 y |
Receiving treatment at time of diagnosis |
Not reported |
Infliximab therapy was discontinued. HL was treated with high-intensity antineo-plastic therapy (unspecified). |
|
10-y-old Female Yildrim- Toruner 200811666 |
HL; stage IIA |
OTH |
3 injections starting at age 3 |
|
Treatment prior to infliximab included: Other Treatment subsequent to infliximab therapy included: Multiple immunosup-pressants |
HL was being treated at time of publication. |
|
5-ASA=5-aminosalicylic acid; 6-MP=6-mercaptopurine; AS=ankylosing
spondylitis; AZA=azathioprine; CD=Crohn’s disease; CMV=cytomegalovirus;
CT=computed tomography; DBCL=diffuse | ||||||
Content on this page was last reviewed on January 31, 2010.
Content on this page was last changed on May 19, 2010.
References:| 8055. | Dossett LA, White LM, Welch DC, et al. Small bowel adenocarcinoma complicating Crohn’s disease: case series and review of the literature. Am Surg. 2007;73(11):1181-1187. |
| 8056. | Smith R, Hicks D, Tomljanovich PI, et al. Adenocarcinoma arising from chronic perianal Crohn’s disease: case report and review of the literature. Am Surg. 2008;74(1):59-61. |
| 8057. | Pimenta EM, Cardozo JB, Santiago MB. Squamous-cell carcinoma of the skin induced by cyclosporin in a patient with rheumatoid arthritis. APLAR J Rheumatol . 2007;10(4):310-312. |
| 11407. | Sanli H, Ataman S, Akay BN, Yilmaz A, Yildizlar D, Gürgey E. Mycosis fungoides in a patient with ankylosing spondylitis during infliximab therapy. J Drugs Dermatol . 2007;6(8):834-836. |
| 11408. | Dauendorffer JN, Rivet J, Allard A, Bachelez H. Sezary syndrome in a patient reciving infliximab for ankylosing spondylitis. Br J Dermatol . 2007;156:(4):742-743. |
| 11575. | Adams AE, Zwicker J, Curiel C, Kabin ME, Falchuk KR, et al. Aggressive cutaneous T-cell lymphomas after TNFα blockade. J Am Acad Dermatol . 2004;51(4):660-662. |
| 11666. | Yildirim-Toruner C, Kimura Y, Rabinovich E. Hodgkin’s lymphoma and tumor necrosis factor inhibitors in juvenile idiopathic arthritis. J Rheumatol . 2008;35(8):1680-1681. |
| 11668. | Girard C, Guillot B, Bessis D. Gastric MALT lymphoma in a patient receiving infliximab for psoriasis. Br J Dermatol . 2008;159(2):497-498. |
| 11669. | Lopez San Roman A, Van Domeselaar M, Redondo C, Arribas R, Rey A. Complete remission of a primary rectal lymphoma on ulcerative colitis, after withdrawal of azathioprine and infliximab. J Crohn’s & Colitis. 2008;2:93-96. |
| 11670. | Lees CW, Ironside J. Wallace WA, Satsagi J. Resolution of non-small-cell lung cancer after withdrawal of anti-TNF therapy. New Engl J Med. 2008;359(3):320-321. |
| 11671. | Nakashima C, Tanioka M, Takahashi K, Miyachi Y. Diffuse large B-cell lymphoma in a patient with rheumatoid arthritis treated with infliximab and methotrexate. Clin Exp Dermatol. 2007;33(4):437-439. |
| 12527. | El Mansouri L, Couchouron T, Le Roux G, et al. Breast cancer in a male with ankylosing spondylitis treated with TNFalpha antagonists. Joint Bone Spine. 2009;76(4):421-423. |
| 12528. | Murakami A. Hepatocellular carcinoma occurring in a young Crohn’s disease patient. Pathology International. 2009;59:492-296 |
| 12529. | Outlaw W, Fleischer A, Bloomfeld R. Lymphomatoid papulosis in a patient with Crohn’s disease treated with infliximab. Inflamm Bowel Dis. 2009;15(7):965-966. |
| 12530. | Zágoni T, Péter Z, Sipos F, et al. Carcinoma arising in enterocutan fistulae of Crohn’s disease patients: description of two cases. Int J Colorectal Dis. 2006;21(5):461-464. |
| 12531. | Khan I, Rahman L, McKenna DB. Primary cutaneous melanoma: a complication of infliximab treatment? Clin Exp Dermatol. 2009;34(4):524-526. |
| 12532. | Jaworski J. Skin melanoma in a rheumatoid arthritis patient treated with infliximab. Reumatologia. 2009;47(2):98-100. |
| 12536. | Melichar B. Anorectal Carcinoma After Infliximab Therapy in Crohn’s Disease: Report of a Case. Dis Colon Rectum. 2006;49:1228-1233 |
| 12537. | Bai M, Katsanos KH, Economou M, et al. Rectal Epstein-Barr virus-positive Hodgkin’s lymphoma in a patient with Crohn’s disease: case report and review of the literature. Scand J Gastroenterol. 2006;41(7):866-869. |
| 12538. | Podolsky DK, Gonzalez RG, Hasserjian RP. Case records of the Massachusetts General Hospital. Case 8-2006. A 71-year-old woman with Crohn’s disease and altered mental status. N Engl J Med. 2006;354(11):1178-1184. |
| 12539. | Lourari S, Prey S, Livideanu C, et al. Cutaneous T-cell lymphoma following treatment of rheumatoid arthritis with tumour necrosis factor-α blocking agents: two cases. J Eur Acad Dermatol Venereol. 2009;23(8):954–982. |
| 12602. | Thonhofer R. Spontaneous remission of marginal zone B cell lymphoma in a patient with seropositive rheumatoid arthritis after discontinuation of infliximab-methotrexate treatment. Ann Rheum Dis 2005;64:1098–1099 |
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Prescribing Information and Medication Guide
REMICADE® (infliximab) Indications and Important Safety Information
INDICATIONS AND USAGE
Crohn’s Disease
REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
REMICADE is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
Ulcerative Colitis
REMICADE is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Rheumatoid Arthritis
REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis
REMICADE is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
Psoriatic Arthritis
REMICADE is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.
Plaque Psoriasis
REMICADE is indicated for the treatment of adult patients with chronic severe (i.e., extensive and /or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. REMICADE should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
IMPORTANT SAFETY INFORMATION
RISK OF INFECTIONS
Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.
Reported infections include:
- Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®. 1,2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic pathogens.
The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE®. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
CONTRAINDICATIONS
REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.
HEPATITIS B REACTIVATION
TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE®. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.
HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥ 5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
HEMATOLOGIC EVENTS
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.
HYPERSENSITIVITY
REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.
NEUROLOGIC EVENTS
TNF inhibitors, including REMICADE®, have been associated with rare cases of new or exacerbated symptoms of demyelinating disorders including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome, seizure, and CNS manifestations of systemic vasculitis. Exercise caution when considering REMICADE® in all patients with these disorders. Consider discontinuation for significant CNS adverse reactions.
AUTOIMMUNITY
Treatment with REMICADE® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
ADVERSE REACTIONS
In clinical trials, the most common REMICADE® adverse reactions occurring in >10% of patients included infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.
USE WITH OTHER DRUGS
The concomitant use of a TNF blocker and anakinra was associated with a higher risk of serious infections, therefore the use of REMICADE® in combination with anakinra is not recommended. Live vaccines should not be given with REMICADE®. Bring pediatric Crohn's patients up to date with all vaccinations prior to initiating REMICADE®.
Please see full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion.
References: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221–S247. 2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.