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Selected Reports |

Treatment of Sarcoidosis With Infliximab* FREE TO VIEW

John D. Doty, MD; Joseph E. Mazur, PharmD; Marc A. Judson, MD, FCCP
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology (Drs. Doty and Judson), and Department of Pharmacy Services, College of Pharmacy (Dr. Mazur), Medical University of South Carolina, Charleston, SC.

Correspondence to: Marc A. Judson, MD, FCCP, Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Medical University of South Carolina, 96 Jonathan Lucas St, Suite 812-CSB, PO Box 250623, Charleston, SC 29425; e-mail: judsonma@musc.edu



Chest. 2005;127(3):1064-1071. doi:10.1378/chest.127.3.1064
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Published online

Background/objectives: Many patients with sarcoidosis are unable to tolerate corticosteroids or alternative therapeutic agents due to side effects or have disease refractory to these agents. We report our experience using infliximab to treat such patients.

Methods: A group of patients in whom traditional sarcoidosis therapy failed, either due to drug failure or intolerable side effects, were prescribed infliximab. Their charts were retrospectively reviewed.

Results: Ten patients receiving infliximab were reviewed. Nine of the 10 patients reported a symptomatic improvement with therapy, and all 10 demonstrated objective evidence of improvement. A drug reaction developed in one patient after several months of therapy, oral candidiasis developed in one patient, and angioimmunoblastic lymphoma developed in another patient. The corticosteroid dose was reduced in five of the six patients who were receiving corticosteroids at the time of infliximab therapy.

Conclusion: Infliximab appears to be an effective, safe treatment for patients with refractory sarcoidosis, including such manifestations as lupus pernio, uveitis, hepatic sarcoidosis, and neurosarcoidosis. Infliximab appears to be steroid sparing. Patients receiving the drug should be screened for latent tuberculosis and lymphoproliferative disorders.

Figures in this Article

The indications for treatment of sarcoidosis are not standardized. There is no Food and Drug Administration-approved therapeutic agent, and response to therapy is variable. Systemic corticosteroids are first-line therapy for patients who require therapy.16 Unfortunately, some patients are unable to tolerate the corticosteroid side effects or are refractory to corticosteroid therapy. Several alternative agents, both cytotoxic and noncytotoxic, have been investigated for use in such patients.4,610 Evidence has demonstrated the critical role of tumor necrosis factor (TNF)-α in the pathogenesis of granulomatous inflammation,11and reports of successful treatment of sarcoidosis with agents having anti-TNF activity have been published.1214 We present here our experience with the TNF-α antagonist infliximab for the treatment of various manifestations of sarcoidosis in patients whose disease was refractory to other agents, or in whom other agents were poorly tolerated due to side effects. Our series adds to a growing body of literature supporting infliximab as an effective agent for sarcoidosis.

Between August 2001 and December 2003, 1,289 visits by 412 patients were documented at our center. A group of patients was identified in whom treatment with standard first- and second-line agents failed and who had been prescribed infliximab, and their charts were retrospectively reviewed. An instrument was developed to define organ involvement in sarcoidosis in the Case Control Etiologic Study of Sarcoidosis,15 a multicenter study to determine the etiology of sarcoidosis. All patients receiving infliximab met the Case Control Etiologic Study of Sarcoidosis criteria for organ involvement in the organ that was being treated. The patients were screened for latent tuberculosis infection by purified protein derivative skin testing. Infliximab was administered at an outpatient center. Initially, patients received 5 mg/kg of infliximab at zero, 2, and 6 weeks. After this induction regimen, dosing was generally done every 8 weeks, but this was variable.

Clinical follow-up was individualized and was tailored to the primary organ system for which infliximab was prescribed. All patients underwent serial physical examinations done by the same examiner (M.A.J.). Patients with lupus pernio or other rashes were photographed at each visit, the patient with uveitis underwent follow-up examinations by an ophthalmologist, the patient with hepatic sarcoidosis underwent serial serum liver panels, and the patients with CNS or bone involvement were followed up using MRI.

Ten patients received infliximab therapy. The baseline characteristics of these patients are listed in Table 1 . Table 2 describes the treatment histories and reviews each individual’s indication for treatment with infliximab. All patients were being treated with prednisone or an alternative agent at the time of infliximab initiation. The duration of therapy with prednisone or other agents prior to infliximab was highly variable. Therapy was either ineffective or intolerable due to drug toxicity or side effects in all patients.

The clinical course of the patients is summarized in Table 3 . Nine of the 10 patients (90%) reported improvement in the symptoms for which infliximab was prescribed. In all 10 patients, objective evidence of improvement was recorded either on physical examination, laboratory studies, or imaging studies. Six patients were receiving corticosteroids prior to infliximab therapy, and this dose was successfully reduced in five of the six patients after therapy.

Patients 1, 6, 7, 8, and 9 were affected by disfiguring lupus pernio lesions. Therapies including prednisone, hydroxychloroquine, and methotrexate had been ineffective. Patient 1 had almost immediate improvement, and prednisone was discontinued after 3 months of infliximab therapy. Complete resolution occurred after 14 total months of therapy, and infliximab was discontinued. She subsequently had a flare-up of a non-lupus pernio skin rash that was managed with hydroxychloroquine. She remains without corticosteroid treatment, and the lupus pernio lesions have not recurred.

In addition to lupus pernio, patient 6 had sarcoidosis of the upper respiratory tract diagnosed several years prior by an otolaryngologist. She complained of sore throat and hoarseness, and her flow-volume loop demonstrated a fixed obstruction pattern. After treatment with infliximab, her lupus pernio improved, and she reported significant improvement in her upper respiratory tract symptoms, particularly hoarseness. Her flow-volume loop did not significantly change with therapy.

Patient 7 had been treated with thalidomide for lupus pernio in the past that did somewhat improve her lesions. Therapy was changed to hydroxychloroquine with worsening of the lupus pernio lesions. Infliximab therapy resulted in improvement far beyond that achieved with thalidomide (Fig 1 ). While the patient was receiving therapy, oral candidiasis developed that responded to nystatin. Patients 8 and 9 also had striking improvement in lupus pernio lesions.

Patient 3 presented with complaints of fever, night sweats, fatigue, pruritus, and right upper quadrant abdominal pain. Her liver was enlarged on physical examination. A serum liver panel revealed a total bilirubin of 2.9 mg/dL; aspartate aminotransferase, 159 IU/L; alanine aminotransferase, 182 IU/L; and alkaline phosphatase, 801 IU/L. Therapy with methylprednisolone and azathioprine was initiated. One month later, her symptoms were unchanged. Laboratory values were notable for an increase of total bilirubin to 5.4 mg/dL, an essentially unchanged alkaline phosphatase of 835 IU/L, and a fall in serum albumin from a normal 3.5 mg/dL to 2.4 mg/dL. Azathioprine was discontinued, and pentoxifylline was added. Six weeks later, her symptoms were still significant. Her total bilirubin level had declined to 2.0 mg/dL, and the aminotransferases had improved somewhat, but the alkaline phosphatase had increased slightly to 1,001 IU/L. Infliximab was then substituted for pentoxifylline. After three doses of infliximab over a 2-month period, her pruritus and fever had resolved. The abdominal tenderness was improved, and the liver reduced to normal size on palpation. The total bilirubin level decreased to the normal range (1.3 mg/dL); aspartate aminotransferase and alanine aminotransferase levels were 89 IU/L and 86 IU/L, respectively; the alkaline phosphatase level had fallen to 725 IU/L; and the serum albumin level returned to the normal range (3.4 mg/dL).

Paresthesias and frequent headaches developed in patient 4 18 months after sarcoidosis was diagnosed. MRI with gadolinium enhancement performed to investigate the new symptoms demonstrated parenchymal and meningeal enhancement in the frontal lobe region. Her symptoms and MRI improved with prednisone, 60 mg/d, but this dose induced psychological side effects including mania and depression. Complete weaning of the prednisone resulted in worsening of her headaches and MRI lesions. She was then started on prednisone at a lower dose (30 mg/d), which did improve the MRI findings, but the side effects persisted and seizures developed at this dose. Infliximab was initiated, and 3 months later she reported resolution of the seizures and improvement in the paresthesias and headaches. MRI at this time showed minimal improvement in the frontal lobe meningeal enhancement. A subsequent MRI performed 9 months later demonstrated resolution of the enhancement (Fig 2 ). She remains clinically well receiving infliximab and 10 mg/d of prednisone.

Patient 5 had a skin rash from sarcoidosis that was controlled with hydroxychloroquine. However, she could only tolerate half the standard dose of hydroxychloroquine, 100 mg bid, due to nausea and vomiting. After 6 years of hydroxychloroquine therapy, her rash worsened and posterior uveitis developed. Infliximab therapy was started; after three doses, her rash had improved. Ophthalmologic evaluation demonstrated resolution of the uveitis. She noted flare-ups of her rash approximately 1 week prior to her scheduled infliximab dose, but these were managed by shortening the interval between doses from 8 to 7 weeks. She remained stable on infliximab for a 1-year period, and then a reaction to the drug developed, consisting of flushing, hypotension, and chest pain. After a 3-month period without the drug, she was rechallenged with infliximab, and the same reaction occurred. Etanercept was then substituted for infliximab. Her uveitis has since recurred, and she requires periodic intraocular corticosteroid injections.

Patients 2 and 10 did not have a dramatic clinical response to infliximab. Five years after her initial diagnosis, incapacitating back pain developed in patient 2. An MRI demonstrated lesions in the T9 and T12 vertebrae that were sampled and demonstrated noncaseating granulomas. Methotrexate was prescribed, and a subsequent MRI showed no improvement. Her symptoms were also unchanged. A mild transaminitis then developed, and infliximab was substituted for methotrexate. After 6 months of infliximab, she continued to have pain. Her MRI showed improvement in the vertebral body lesions (Fig 3 ) but also showed a previously unappreciated disk herniation. Her pain was attributed to the disk disease, and infliximab was discontinued. Sixteen years prior to treatment with infliximab, Bell palsy and uveitis developed in patient 10, which were treated with prednisone. Three years after these initial symptoms, pain and edema of the right knee and proximal right lower extremity developed. A muscle biopsy was eventually performed and showed granulomatous myositis. The patient also had an almost 20-year history of an ill-defined lymphoproliferative disorder that had not required therapy. The dose of prednisone required to manage his leg symptoms was 30 mg/d at the time infliximab was prescribed. He initially had a good response to the drug, with improvement in symptoms, leg edema, and mobility. The prednisone was reduced to 15 mg/d. Despite the subjective improvement, MRI findings of the lower extremity worsened. While the patient was receiving infliximab, angioimmunoblastic lymphoma developed.

The pathologic hallmark of sarcoidosis is the nonnecrotizing granuloma, which consists of a compact central core of macrophage-derived epithelioid and multinucleated giant cells surrounded peripherally by lymphocytes, monocytes, and fibroblasts.16 The chemokine and cytokine pathways that regulate granuloma formation are not well understood, but TNF-α is known to play a key role.11,17Further, TNF-α production by alveolar macrophages in patients with sarcoidosis is known to be substantially elevated.1819 The use of the TNF-α antagonists pentoxifylline and thalidomide has been reported to be effective in the treatment of refractory manifestations of sarcoidosis.1214 This article describes our experience using infliximab, a chimeric monoclonal antibody against TNF-α for this purpose.

Currently, infliximab is approved for the treatment of rheumatoid arthritis and Crohn disease. Several small case series have been published reporting the efficacy of infliximab for treating sarcoidosis of the skin (including lupus pernio),14,2023 eyes,14,24CNS,25 GI tract and liver,14,26 and lungs.14,20 Our series is the largest to date in the medical literature to describe the use of infliximab for refractory sarcoidosis.

In five of our patients, lupus pernio was the indication for treatment. In most patients, the response of the lupus pernio lesions to infliximab was dramatic (Fig 1). An additional patient was administered infliximab for a non-lupus pernio skin rash that also responded well. The uveitis in patient 5 resolved with infliximab, and the uveitis flared up when the drug was discontinued. The hepatic sarcoidosis seen in patient 3 improved, as did the neurosarcoidosis of patient 4 (Fig 2). To our knowledge, this is the first time infliximab has been successful in treating sarcoidosis of the upper respiratory tract (patient 6). In a previous report,26infliximab was efficacious in treating bony lesions and granulomatous myositis, as it was in two of our patients (patients 2 and 10). Six of our patients were receiving corticosteroids when infliximab was initiated, and the dose was successfully reduced in five of the six. Etanercept, another TNF-α antagonist, was ineffective in controlling the uveitis in patient 5. Interestingly, etanercept failure for ocular disease has been previously described,27as has etanercept failure for stage II and III pulmonary sarcoidosis.28Infliximab is highly specific for TNF-α, whereas etanercept also binds a related molecule, lymphotoxin-α (formerly known as TNF-β). The molecular structure as an IgG antibody of infliximab allows it to initiate the classical complement pathway and cause cell lysis, whereas etanercept, a recombinant molecule attached to the Fc portion of human IgG1, cannot. Moreover, infliximab has been demonstrated to induce T-cell apoptosis, and etanercept has not.29 The reasons for the enhanced efficacy of infliximab in sarcoidosis are not well understood, but certainly one of the above properties could explain the difference.

In the series published to date, infliximab demonstrates a very low occurrence of adverse effects.1925 Similarly, it was well tolerated in our patient population with the exception of patient 5, who received the drug for over a year before anaphylaxis-like symptoms developed. This reaction was not investigated further, but it was likely due to the presence of human antichimeric antibodies, which can develop after repeated treatment with infliximab. In a study30evaluating the use of infliximab for treatment of Crohn disease, the incidence of antibody formation to infliximab was significantly reduced by using an induction dosing regimen of zero, 2, and 6 weeks, followed by maintenance therapy every 8 weeks. Patient 5 did not receive this exact regimen. After the standard induction doses, she received infliximab on an every-4-week basis for three additional doses (Table 3). Additionally, Baert et al31 found that concomitant therapy with immunosuppressive agents reduces the magnitude of the immunologic response to infliximab infusion. Patient 5 was not receiving immunosuppressive agents at the time of her infliximab therapy.

A well-described and serious side effect of infliximab use is the reactivation of latent tuberculosis infection,32and the reactivation of another granulomatous infection, histoplasmosis, has been described.33 All our patients were carefully screened for latent tuberculosis prior to infliximab infusion, and this side effect was not observed in our review. We also did not note reactivation of latent histoplasmosis, but coastal South Carolina is not an endemic area for this organism. Oral candidiasis developed in patient 7 while she was receiving the drug, but she was receiving inhaled beclomethasone concurrently. Further, we did not observe the development of a hypercoagulable state in association with the drug, as described by Yee and Pochapin.26

Patient 10 in our series had an almost 20-year history of an indolent, ill-defined lymphoproliferative disorder, and he acquired angioimmunoblastic lymphoma while receiving infliximab. The potential association between TNF-α antagonist therapy and the development of lymphoma in patients with rheumatoid arthritis and Crohn disease is well described.34 A definitive causal relationship cannot be established, especially given the predisposition to lymphoma in patients with these conditions. However, the potential role of infliximab in the progression of our patient’s hematologic disease course cannot be discounted.

In summary, the TNF-α antagonist infliximab seems to be useful not only in the treatment of lupus pernio and other cutaneous manifestations of sarcoidosis, but also in treating other serious complications of the disease, including uveitis and CNS disease. Infliximab appears to be steroid sparing, and is generally well tolerated by patients. As pulmonary disease was not the principle indication for therapy in any of our 10 patients, no data regarding the changes in chest radiographs or spirometric parameters before and after infliximab were collected, but these data should be evaluated in future investigations with this agent. Although multicenter trials are needed to validate our findings and the findings of other investigators, our experience with this drug suggests that infliximab is a reasonable alternative agent for use in treating refractory sarcoidosis. Clinicians in endemic areas should be mindful of the potential for latent Histoplasmosis reactivation, and the agent should be used with caution in patients with potential lymphoproliferative disorders. Importantly, patients selected to receive infliximab for any granulomatous disorder must be carefully screened for latent tuberculosis infection.

The authors wish to thank James G. Ravenel, MD, Department of Radiology, Medical University of South Carolina, for reviewing the MRIs displayed in this article.

Abbreviation: TNF = tumor necrosis factor

Dr. Judson serves on the medical advisory board for Centocor Pharmaceuticals.

Table Graphic Jump Location
Table 1. Baseline Characteristics (n = 10)
Table Graphic Jump Location
Table 2. Prior Therapies and Indications for Infliximab*
* 

SURT = sarcoidosis of the upper respiratory tract. LP = lupus pernio.

Table Graphic Jump Location
Table 3. Clinical Course*
* 

RLE = right lower extremity; N/A = not applicable; RUQ = right upper quadrant. See Table 2 for expansion of abbreviation.

 

Therapy is ongoing at the time of this article.

Figure Jump LinkFigure 1. Photographs of patient 7 before (top) and after (bottom) infliximab therapy for lupus pernio (photograph used with patient permission).Grahic Jump Location
Figure Jump LinkFigure 2. Gadolinium-enhanced MRI demonstrating improvement in CNS lesions before (left) and after (right) infliximab therapy.Grahic Jump Location
Figure Jump LinkFigure 3. Spin echo gadolinium-enhanced MRI demonstrating a T12 vertebral body sarcoid lesion (arrows) before infliximab therapy (left) and after infliximab therapy (right). The lesion is less conspicuous after therapy.Grahic Jump Location
Winterbauer, RH, Kirtland, SH, Corey, DE (1997) Treatment with corticosteroids.Clin Chest Med18,843-851. [CrossRef] [PubMed]
 
Judson, MA An approach to the treatment of pulmonary sarcoidosis with corticosteroids.Chest1999;111,623-631
 
Yazaki, Y, Isobe, M, Hiroe, M, et al Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone.Am J Cardiol2001;88,1006-1010. [CrossRef] [PubMed]
 
Lower, EE, Broderick, JP, Brott, TG, et al Diagnosis and management of neurological sarcoidosis.Arch Intern Med1997;157,1864-1868. [CrossRef] [PubMed]
 
Bradley, D, Baughman, RP, Raymond, L, et al Ocular manifestations of sarcoidosis.Semin Respir Crit Care Med2002;23,543-548. [CrossRef] [PubMed]
 
Mana, J, Marcoval, J, Graells, J, et al Cutaneous involvement in sarcoidosis: relationship to systemic disease.Arch Dermatol1997;133,882-888. [CrossRef] [PubMed]
 
Baughman, RP, Lower, EE Steroid-sparing alternative treatments for sarcoidosis.Clin Chest Med1997;18,853-864. [CrossRef] [PubMed]
 
Lower, EE, Baughman, RP The use of low-dose methotrexate in refractory sarcoidosis.Am J Med Sci1990;299,153-157. [CrossRef] [PubMed]
 
Sharma, OP, Vucinic, V Sarcoidosis of the thyroid and kidneys and calcium metabolism.Semin Respir Crit Care Med2002;23,579-588. [CrossRef] [PubMed]
 
Doty, JD, Mazur, JE, Judson, MA Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen.Chest2003;124,2023-2026. [CrossRef] [PubMed]
 
Roach, DR, Bean, AG, Demangel, C, et al TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection.J Immunol2002;168,4620-4627. [PubMed]
 
Zabel, P, Entzian, P, Dalhoff, K, et al Pentoxifylline in treatment of sarcoidosis.Am J Respir Crit Care Med1997;155,1665-1669. [PubMed]
 
Baughman, RP, Judson, MA, Teirstein, AS, et al Thalidomide for chronic sarcoidosis.Chest2002;122,227-232. [CrossRef] [PubMed]
 
Pritchard, C, Nadarajah, K Tumour necrosis factor-α inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients.Ann Rheum Dis2004;63,318-320. [CrossRef] [PubMed]
 
Judson, MA, Baughman, RP, Tierstein, AS, et al Defining organ involvement in sarcoidosis: the ACCESS proposed instrument.Sarc Vasc Diffuse Lung Dis1999;16,75-86
 
Thomas, PD, Hunninghake, GW Current concepts of the pathogenesis of sarcoidosis.Am Rev Respir Dis1987;135,747-760. [PubMed]
 
Kindler, V, Sappino, AP, Grau, GE, et al The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection.Cell1989;56,731-740. [CrossRef] [PubMed]
 
Zheng, L, Tescheler, H, Guzman, J, et al Alveolar macrophage TNF-α release and BAL cell phenotypes in sarcoidosis.Am J Respir Crit Care Med1995;152,1061-1066. [PubMed]
 
Baughman, RP, Strohofer, SA, Buchsbaum, J, et al Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis.J Lab Clin Med1990;115,36-42. [PubMed]
 
Baughman, RP, Lower, EE Infliximab for refractory sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis2001;18,70-74. [PubMed]
 
Mallbris, L, Ljungberg, A, Hedblad, M, et al Progressive cutaneous sarcoidosis responding to anti-tumor necrosis factor-α therapy.J Am Acad Dermatol2003;48,290-293. [CrossRef] [PubMed]
 
Meyerle, JH, Shorr, A The use of infliximab in cutaneous sarcoidosis.J Drugs Dermatol2003;2,413-414. [PubMed]
 
Roberts, SD, Wilkes, DS, Burgett, RA, et al Refractory sarcoidosis responding to infliximab.Chest2003;124,2028-2031. [CrossRef] [PubMed]
 
Katz, JM, Bruno, MK, Winterkorn, JMS, et al The pathogenesis and treatment of optic disc swelling in neurosarcoidosis: a unique therapeutic response to infliximab.Arch Neurol;60,426-430. [CrossRef] [PubMed]
 
Pettersen, JA, Zochodne, DW, Bell, RB, et al Refractory neurosarcoidosis responding to infliximab.Neurology2002;59,1660-1661. [CrossRef] [PubMed]
 
Yee, AMF, Pochapin, MB Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-α therapy.Ann Intern Med2001;135,27-31. [PubMed]
 
Baughman, RP, Bradley, DA, Raymond, LA, et al Double-blind, randomized trial of a tumor necrosis factor receptor antagonist (etanercept) for treatment of chronic ocular sarcoidosis [abstract]. Am J Respir Crit Care Med. 2002;;165 ,.:A495
 
Utz, JP, Limper, AH, Kalra, S, et al Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis.Chest2003;124,177-185. [CrossRef] [PubMed]
 
Calabrese, LH Molecular differences in anticytokine therapies.Clin Exp Rheumatol2003;21,241-248. [PubMed]
 
Wagner, C, Olson, A, Ford, J, et al Effects of antibodies to infliximab on safety and efficacy of infliximab treatment in patients with Crohn’s disease [abstract].Gastroenterology2002;122(suppl),A613-A614
 
Baert, F, Noman, M, Vermeire, S, et al Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease.N Engl J Med2003;348,601-608. [CrossRef] [PubMed]
 
Keane, J, Gershon, S, Wise, RP, et al Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent.N Engl J Med2001;345,1098-1104. [CrossRef] [PubMed]
 
Wood, KL, Hage, CA, Knox, KS, et al Histoplasmosis after treatment with anti-tumor necrosis factor-α therapy.Am J Respir Crit Care Med2003;167,1279-1282. [CrossRef] [PubMed]
 
Brown, SL, Greene, MH, Gershon, SK, et al Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.Arthritis Rheum2002;46,3151-3158. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Photographs of patient 7 before (top) and after (bottom) infliximab therapy for lupus pernio (photograph used with patient permission).Grahic Jump Location
Figure Jump LinkFigure 2. Gadolinium-enhanced MRI demonstrating improvement in CNS lesions before (left) and after (right) infliximab therapy.Grahic Jump Location
Figure Jump LinkFigure 3. Spin echo gadolinium-enhanced MRI demonstrating a T12 vertebral body sarcoid lesion (arrows) before infliximab therapy (left) and after infliximab therapy (right). The lesion is less conspicuous after therapy.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Baseline Characteristics (n = 10)
Table Graphic Jump Location
Table 2. Prior Therapies and Indications for Infliximab*
* 

SURT = sarcoidosis of the upper respiratory tract. LP = lupus pernio.

Table Graphic Jump Location
Table 3. Clinical Course*
* 

RLE = right lower extremity; N/A = not applicable; RUQ = right upper quadrant. See Table 2 for expansion of abbreviation.

 

Therapy is ongoing at the time of this article.

References

Winterbauer, RH, Kirtland, SH, Corey, DE (1997) Treatment with corticosteroids.Clin Chest Med18,843-851. [CrossRef] [PubMed]
 
Judson, MA An approach to the treatment of pulmonary sarcoidosis with corticosteroids.Chest1999;111,623-631
 
Yazaki, Y, Isobe, M, Hiroe, M, et al Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone.Am J Cardiol2001;88,1006-1010. [CrossRef] [PubMed]
 
Lower, EE, Broderick, JP, Brott, TG, et al Diagnosis and management of neurological sarcoidosis.Arch Intern Med1997;157,1864-1868. [CrossRef] [PubMed]
 
Bradley, D, Baughman, RP, Raymond, L, et al Ocular manifestations of sarcoidosis.Semin Respir Crit Care Med2002;23,543-548. [CrossRef] [PubMed]
 
Mana, J, Marcoval, J, Graells, J, et al Cutaneous involvement in sarcoidosis: relationship to systemic disease.Arch Dermatol1997;133,882-888. [CrossRef] [PubMed]
 
Baughman, RP, Lower, EE Steroid-sparing alternative treatments for sarcoidosis.Clin Chest Med1997;18,853-864. [CrossRef] [PubMed]
 
Lower, EE, Baughman, RP The use of low-dose methotrexate in refractory sarcoidosis.Am J Med Sci1990;299,153-157. [CrossRef] [PubMed]
 
Sharma, OP, Vucinic, V Sarcoidosis of the thyroid and kidneys and calcium metabolism.Semin Respir Crit Care Med2002;23,579-588. [CrossRef] [PubMed]
 
Doty, JD, Mazur, JE, Judson, MA Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen.Chest2003;124,2023-2026. [CrossRef] [PubMed]
 
Roach, DR, Bean, AG, Demangel, C, et al TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection.J Immunol2002;168,4620-4627. [PubMed]
 
Zabel, P, Entzian, P, Dalhoff, K, et al Pentoxifylline in treatment of sarcoidosis.Am J Respir Crit Care Med1997;155,1665-1669. [PubMed]
 
Baughman, RP, Judson, MA, Teirstein, AS, et al Thalidomide for chronic sarcoidosis.Chest2002;122,227-232. [CrossRef] [PubMed]
 
Pritchard, C, Nadarajah, K Tumour necrosis factor-α inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients.Ann Rheum Dis2004;63,318-320. [CrossRef] [PubMed]
 
Judson, MA, Baughman, RP, Tierstein, AS, et al Defining organ involvement in sarcoidosis: the ACCESS proposed instrument.Sarc Vasc Diffuse Lung Dis1999;16,75-86
 
Thomas, PD, Hunninghake, GW Current concepts of the pathogenesis of sarcoidosis.Am Rev Respir Dis1987;135,747-760. [PubMed]
 
Kindler, V, Sappino, AP, Grau, GE, et al The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection.Cell1989;56,731-740. [CrossRef] [PubMed]
 
Zheng, L, Tescheler, H, Guzman, J, et al Alveolar macrophage TNF-α release and BAL cell phenotypes in sarcoidosis.Am J Respir Crit Care Med1995;152,1061-1066. [PubMed]
 
Baughman, RP, Strohofer, SA, Buchsbaum, J, et al Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis.J Lab Clin Med1990;115,36-42. [PubMed]
 
Baughman, RP, Lower, EE Infliximab for refractory sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis2001;18,70-74. [PubMed]
 
Mallbris, L, Ljungberg, A, Hedblad, M, et al Progressive cutaneous sarcoidosis responding to anti-tumor necrosis factor-α therapy.J Am Acad Dermatol2003;48,290-293. [CrossRef] [PubMed]
 
Meyerle, JH, Shorr, A The use of infliximab in cutaneous sarcoidosis.J Drugs Dermatol2003;2,413-414. [PubMed]
 
Roberts, SD, Wilkes, DS, Burgett, RA, et al Refractory sarcoidosis responding to infliximab.Chest2003;124,2028-2031. [CrossRef] [PubMed]
 
Katz, JM, Bruno, MK, Winterkorn, JMS, et al The pathogenesis and treatment of optic disc swelling in neurosarcoidosis: a unique therapeutic response to infliximab.Arch Neurol;60,426-430. [CrossRef] [PubMed]
 
Pettersen, JA, Zochodne, DW, Bell, RB, et al Refractory neurosarcoidosis responding to infliximab.Neurology2002;59,1660-1661. [CrossRef] [PubMed]
 
Yee, AMF, Pochapin, MB Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-α therapy.Ann Intern Med2001;135,27-31. [PubMed]
 
Baughman, RP, Bradley, DA, Raymond, LA, et al Double-blind, randomized trial of a tumor necrosis factor receptor antagonist (etanercept) for treatment of chronic ocular sarcoidosis [abstract]. Am J Respir Crit Care Med. 2002;;165 ,.:A495
 
Utz, JP, Limper, AH, Kalra, S, et al Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis.Chest2003;124,177-185. [CrossRef] [PubMed]
 
Calabrese, LH Molecular differences in anticytokine therapies.Clin Exp Rheumatol2003;21,241-248. [PubMed]
 
Wagner, C, Olson, A, Ford, J, et al Effects of antibodies to infliximab on safety and efficacy of infliximab treatment in patients with Crohn’s disease [abstract].Gastroenterology2002;122(suppl),A613-A614
 
Baert, F, Noman, M, Vermeire, S, et al Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease.N Engl J Med2003;348,601-608. [CrossRef] [PubMed]
 
Keane, J, Gershon, S, Wise, RP, et al Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent.N Engl J Med2001;345,1098-1104. [CrossRef] [PubMed]
 
Wood, KL, Hage, CA, Knox, KS, et al Histoplasmosis after treatment with anti-tumor necrosis factor-α therapy.Am J Respir Crit Care Med2003;167,1279-1282. [CrossRef] [PubMed]
 
Brown, SL, Greene, MH, Gershon, SK, et al Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.Arthritis Rheum2002;46,3151-3158. [CrossRef] [PubMed]
 
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