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Multicentric Reticulohistiocytosis Successfully Treated With Infliximab:  An Illustrative Case and Evaluation of Cytokine Expression Supporting Anti–Tumor Necrosis Factor Therapy FREE

Andrew H. Kalajian, MD; Jeffrey P. Callen, MD
[+] Author Affiliations

Author Affiliations: Division of Dermatology, Department of Medicine, University of Louisville, Louisville, Kentucky.


Arch Dermatol. 2008;144(10):1360-1366. doi:10.1001/archderm.144.10.1360.
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Published online

Background  Multicentric reticulohistiocytosis (MR) is a rare multisystem granulomatous disease that frequently results in disfiguring cutaneous deposition, destructive arthritis, and debilitating constitutional symptoms. No consistently effective treatment has been identified. Recently, studies characterizing the cytokine expression profile in MR have prompted therapeutic attempts with tumor necrosis factor (TNF) inhibition. Owing to the rarity of the condition, few such cases have been reported, and controlled studies are unlikely to be performed.

Observations  A 63-year-old man developed MR refractory to traditional therapies and etanercept therapy. The addition of infliximab to his current regimen of methotrexate sodium and prednisone resulted in a rapid and sustained improvement in his cutaneous, articular, and constitutional manifestations of disease throughout 12 months of follow-up.

Conclusions  We present this case to highlight the growing body of evidence characterizing the cytokine involvement in MR that has led to successful therapy via TNF inhibition. Our patient responded dramatically to infliximab in combination with methotrexate and prednisone despite previously failing to benefit from etanercept therapy. An analysis of our case combined with those previously reported in the literature suggests that despite some disparity in the response of cutaneous and articular manifestations of MR, TNF blockade is emerging as a promising therapeutic option.

Figures in this Article

Multicentric reticulohistiocytosis (MR) is a rare multisystem granulomatous disease manifesting cutaneous eruption, destructive arthritis, various systemic involvement, and associated malignancy. The cause has not been fully elucidated, and no consistently effective treatment has been identified. We describe a patient with disfiguring cutaneous involvement and aggressive destructive deforming arthritis refractory to numerous therapies including tumor necrosis factor (TNF) inhibition with etanercept, who responded dramatically to treatment with infliximab. We discuss herein the evidence supporting treatment of MR with TNF inhibition and evaluate the few published cases of MR treatment with TNF inhibition.

A previously healthy 63-year-old man was referred for treatment of refractory multicentric reticulohistiocytosis (MR). One year previously, he developed asymptomatic cutaneous lesions followed by the onset of a progressively destructive arthritis, positive purified protein derivative, episodic fevers, night sweats, and 30-kg weight loss. Malignancy evaluation, consisting of prostate specific antigen, digital rectal examination, colonoscopy, esophagogastroduodenoscopy, and computed tomographic scans of the chest, abdomen, and pelvis, was negative. Tuberculosis was excluded via chest radiography and sputum smears and culture. He was treated with varying doses of oral prednisone (up to 60 mg/d) for 10 months, isoniazid (300 mg/d by mouth for 6 months), methotrexate sodium (7.5 mg by mouth, weekly for 10 months, then changed to 15 mg intramuscularly, weekly for the past month), and etanercept (50 mg subcutaneous injections weekly) for the past 4 months (Figure 1). His condition deteriorated despite these treatments, and he was seen at our clinic.

Place holder to copy figure label and caption
Figure 1.

Treatment regimen prior to our initial evaluation. At time point 0, we initiated infliximab therapy in place of etanercept therapy, while continuing methotrexate sodium, prednisone, and isoniazid therapies.

Graphic Jump Location

Our initial physical examination revealed a frail man appearing older than his age, who ambulated with an unsteady gait requiring the assistance of a walker. Cutaneous examination revealed firm, flesh-colored to deeply erythematous papules and nodules on his hands, fingers, ears, nares (acral distribution), and oral mucosa, and small papules overlying a poikilodermatous patch on his right chest (Figure 2). Tender inflammation and limited range of motion of his knees, ankles, shoulders, wrists, and hands were prominent. Several fingers displayed moderate contracture deformity. He provided photographs of the arthroscopic examination of his right knee (Figure 3). Histopathologic evaluation of both a papule and portion of the patch from his right chest revealed dermal infiltration with multinucleated giant cells with an amorphous, eosinophilic, “ground-glass”–appearing cytoplasm, varying only in density of infiltration (Figure 4). Laboratory evaluation revealed an elevated creatine kinase level of 350 U/L (reference range, 24-204 U/L) (to convert to microkatals per liter, multiply by 0.0167), a C-reactive protein level of 21.9 mg/L (reference range, 0-4.9 mg/L) (to convert to nanomoles per liter, multiply by 9.524), and an erythrocyte sedimentation rate or 21 mm/h (reference range, 0-20 mm/h). Results from the following evaluations were negative or normal: complete blood cell count, comprehensive metabolic panel, thyroid panel, serum protein electrophoresis, serum immunofixation electrophoresis, antineutrophilic cytoplasmic antibody, anticardiolipin antibody, β-2 glycoprotein 1 antibody, rheumatoid factor, antinuclear antibody, anti–double-stranded DNA antibody, and hepatitis C antibody.

Place holder to copy figure label and caption
Figure 2.

Clinical appearance on initial examination revealed a poikilodermatous patch on his right chest (A), as well as firm, flesh-colored to deeply erythematous papules and nodules on his hands, fingers (B), ears (C), nares (D), and oral mucosa.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Arthroscopic image of knee revealing significant articular destruction from multicentric reticulohistiocytosis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Skin biopsy specimen showing dermal infiltration with multinucleated giant cells with an amorphous, eosinophilic, “ground-glass”– appearing cytoplasm (hematoxylin-eosin, original magnifications ×100 [main] and ×600 [inset]).

Graphic Jump Location

We agreed on the diagnosis of MR and initiated treatment with infliximab (5-mg/kg infusion at weeks 0, 2, and 6 and then every 8 weeks) in place of etanercept, while continuing prednisone and methotrexate therapies at prior doses. After 3 infusions, he noted improvement of his fatigue and malaise, resolution of the poikilodermatous patch on his right chest, cessation of new cutaneous lesions, and decreased prominence of his existing lesions (Figure 5A). His weight returned to baseline, and his arthritis improved, which, combined with a right total knee replacement, provided significantly improved quality of life manifested by the ability to walk unassisted and perform routine duties at home. His oral prednisone dosage was slowly tapered to 7.5 mg/d. After 5 infusions, his benefit appeared to plateau, and the interval between infliximab infusions was shortened to 6 weeks. His cutaneous manifestations continued to show progressive improvement over the next 12 months, with a near resolution of all but the largest nodules (Figure 5B-D); he has not developed new cutaneous lesions since starting infliximab therapy. However, he continues to experience fluctuations of mild fatigue and arthralgias despite continuing treatments with infliximab (5 mg/kg every 5 weeks), methotrexate sodium (15 mg intramuscularly each week), and oral prednisone (7.5 mg/d). These fluctuating constitutional and articular symptoms are temporally associated with periods of more strenuous physical activity and bear no relationship to the timing of his infliximab infusions. Despite near resolution of his cutaneous deposits and dramatic improvement in his constitutional and articular manifestations of disease, significant joint contractures and deformities of his fingers and hands remain. He has not experienced any adverse effects from his medication regimen.

Place holder to copy figure label and caption
Figure 5.

Resolution of poikilodermatous patch on right chest after 3 infliximab infusions (A), and near complete resolution of cutaneous papules on fingers (B), ears (C), and nares (D) after 7 months of receiving infliximab, methotrexate sodium, and prednisone therapies.

Graphic Jump Location

Multicentric reticulohistiocytosis most frequently affects the skin and joints; however, as a systemic disease, MR can affect nearly any organ.1 Cutaneous involvement favors an acral distribution of flesh-colored to deeply erythematous firm papules and nodules which, when involving the periungual area, often assumes a “coral-bead” appearance. Mucosal involvement is observed in 30% of cases, and a poikilodermatous eruption over the trunk has been described.24 Histopathologic findings are similar in both skin and synovium, revealing CD68-positive histiocytic infiltrate with multinucleated giant cells with an eosinophilic finely granulated “ground-glass”–appearing cytoplasm.1 A symmetric, destructive polyarthritis with radiographic erosive changes, often disproportionately severe in comparison with clinical examination, progresses to arthritis mutilans in 30% to 50% of cases.1,4,5 An associated malignant neoplasm is identified in 20% to 30%; however, while a thorough search for associated malignant neoplasms is indicated, MR is not considered a true paraneoplastic disease because it does not commonly parallel the course of the associated malignant neoplasm, and no specific malignant disorder has been identified.1,6,7 Constitutional symptoms are observed in 5% to 10% of patients, autoimmune disease in 6% to 16%, and purified protein derivative testing is reactive in up to 50% of patients, leading to proposed causative mechanisms involving abnormal histiocytic reactions to an associated mycobacterial infection, autoimmune process, or neoplastic process.1,5,8

The cause of MR is not clear, and to date, no consistently effective treatment has been identified. The therapeutic search is complicated by the rarity of the disease, intrinsic fluctuation of disease activity, and the tendency for spontaneous remission after 5 to 10 years; however, in most patients this occurs after cutaneous disfigurement and irreversible joint destruction has developed.1,5 Limited success has been observed with nonsteroidal anti-inflammatory medications, corticosteroids, isoniazid, methotrexate, cyclosporine, cyclophosphamide, and chlorambucil.9

The histiocytic infiltrate observed in MR has been shown to be of monocyte-macrophage origin, with positive staining results for CD14, CD68, and HLA-DR antigens.8,1012 More recent studies have demonstrated monocyte-macrophage–derived cytokines, including TNF, interleukin (IL)-1, IL-6, IL-12, prostaglandin E2, and platelet-derived growth factor β to be expressed.8,10,12,13 These proinflammatory cytokines are also causally involved in rheumatoid arthritis and psoriatic arthritis, 2 diseases in which TNF inhibition has proven therapeutic.14 Inhibition of TNF has also proven beneficial in granulomatous diseases such as sarcoidosis, granuloma annulare, and necrobiosis lipoidica.1519 Coupling the recently characterized proinflammatory cytokine profile with the benefit from TNF blockade in similar disease processes has led to therapeutic trials of anti-TNF agents in MR.

Matejicka et al20 were the first to report the treatment of MR with TNF inhibition when they described a 22-year-old woman who was refractory to numerous therapies over the prior 3 years and experienced a dramatic clinical and radiographic improvement in cutaneous and articular manifestations of MR just 6 weeks after adding etanercept, 25 mg twice weekly, to her regimen. There have since been additional reports of treatment success in MR using TNF inhibition with etanercept, adalimumab, and infliximab (Table 1).2123 Kovach et al21 described a patient with a dramatic response of both cutaneous and articular manifestations after etanercept was added to prednisone and methotrexate therapies. They commented that progression of his articular deformities despite control of his synovitis was likely due to articular damage that had previously occurred. Interestingly, Shannon et al23 described a case of a 37-year-old renal transplantation patient who developed articular manifestations of MR despite long-term immunosuppression with prednisone, mycophenolate mofetil, and cyclosporine. She experienced a rapid resolution of her isolated articular MR with adalimumab therapy.

Table Graphic Jump LocationTable 1. Previous Reports of Therapeutic Success With Tumor Necrosis Factor (TNF) Inhibition in Multicentric Reticulohistiocytosis

However, TNF inhibition has not been uniformly effective in the treatment of MR (Table 2).24,25 Sellam et al24 reported 2 cases of MR treated with infliximab, which resulted in dramatic improvement in cutaneous lesions but minimal to no improvement in articular disease. One of the patients was later switched to etanercept therapy, which also failed to improve the joint disease. Lovelace et al25 described a patient who failed to improve with etanercept and intramuscular triamcinolone acetonide therapies and postulated that perhaps concomitant treatment with TNF inhibition, methotrexate, and corticosteroids is required for therapeutic success. On review of the relatively small number of previously reported cases of MR treated with TNF blockade, there appears to be a trend toward success in those patients treated simultaneously with TNF inhibition, prednisone, and methotrexate.2025

Table Graphic Jump LocationTable 2. Previous Reports of Less Effective Therapy With Tumor Necrosis Factor (TNF) Inhibition in Multicentric Reticulohistiocytosis

While our patient's disease is not in total remission, he experienced a dramatic improvement in both cutaneous and articular manifestations of MR after receiving 3 infusions of infliximab while continuing his prior regimen of methotrexate and prednisone. He has achieved a sustained response, and his skin is nearly clear after 12 months of continued therapy; he attributes his significantly improved quality of life to the addition of infliximab. Similar to the patient described by Kovach et al,21 our patient noted increased articular deformity of his hands shortly after control of his synovitis. Subsequently, he has not experienced any further articular deformity. We believe that his deformity was due to previous articular damage and suggest that the true extent of joint destruction in MR may only be appreciated after synovitis is quiescent.

Response to infliximab therapy despite failure of etanercept therapy in our patient may be explained by the differential binding to TNF. Infliximab has a high association rate and a low dissociation rate, thus binding to TNF quickly and irreversibly as compared with etanercept, which has a high dissociation rate for both soluble and transmembrane TNF. Complete neutralization of TNF via infliximab therapy would result in the cessation of inflammatory cell recruitment and thus disruption of granuloma integrity, whereas the partial inhibition of TNF via etanercept therapy would not be effective in granuloma disruption.26

While the interval between infliximab infusions has been progressively shortened, there is no temporal correlation between disease severity and infliximab infusions; rather, it appears that his symptom fluctuation may be due to spontaneous fluctuations typical of MR or to his varying activity level. Nonetheless, it would not be surprising that dose escalation may be required for the long-term treatment of MR, a phenomenon frequently observed in psoriatic patients treated with infliximab.27 In addition, the association of TNF inhibition with increased risk of malignant neoplasms and serious infections is well documented.28 Therefore, thorough evaluation to exclude coexistent malignant disease or infection, especially considering the frequency of purified protein derivative reactivity in MR, is required prior to initiating treatment with TNF inhibition.

We present this case to highlight the growing body of evidence characterizing the cytokine involvement in MR that has led to successful therapy via TNF inhibition. While prior reports have documented success with etanercept therapy, our patient failed to improve with etanercept therapy but demonstrated a rapid and sustained response to infliximab therapy throughout 12 months of treatment. An analysis of our case and those previously reported in the literature suggests that despite some disparity in the response of cutaneous and articular manifestations of MR, TNF blockade is emerging as a promising therapeutic option. Since controlled studies examining the benefit of TNF inhibition in MR are unlikely to occur owing to the rarity of the disease, we encourage the reporting of treatment successes and failures for this devastating disease.

Correspondence: Andrew H. Kalajian, MD, Division of Dermatology, Department of Medicine, University of Louisville, 310 E Broadway, Floor 2A, Louisville, KY 40202 (akalajian@yahoo.com).

Accepted for Publication: December 30, 2007.

Author Contributions: Both authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kalajian and Callen. Acquisition of data: Kalajian. Analysis and interpretation of data: Kalajian and Callen. Drafting of the manuscript: Kalajian. Critical revision of the manuscript for important intellectual content: Kalajian and Callen. Study supervision: Kalajian and Callen.

Financial Disclosure: None reported.

Luz  FBGaspar  APKalil-Gaspar  N  et al.  Multicentric reticulohistiocytosis. J Eur Acad Dermatol Venereol 2001;15 (6) 524- 531
PubMed
Hiramanek  NKossard  SBarnetson  RS Multicentric reticulohistiocytosis presenting with a rash and arthralgia. Australas J Dermatol 2002;43 (2) 136- 139
PubMed
Hsiung  SHChan  EFElenitsas  R  et al.  Multicentric reticulohistiocytosis presenting with clinical features of dermatomyositis. J Am Acad Dermatol 2003;48 (2) ((suppl)) S11- S14
PubMed
Tajirian  ALMalik  MKRobinson-Bostom  L  et al.  Multicentric reticulohistiocytosis. Clin Dermatol 2006;24 (6) 486- 492
PubMed
Lesher  JLAllen  BS Multicentric reticulohistiocytosis. J Am Acad Dermatol 1984;11 (4, pt 2) 713- 723
PubMed
Kurzrock  RCohen  PR Cutaneous paraneoplastic syndromes in solid tumors. Am J Med 1995;99 (6) 662- 671
PubMed
Catterall  MDWhite  JE Multicentric reticulohistiocytosis and malignant disease. Br J Dermatol 1978;98 (2) 221- 224
PubMed
Gorman  JDDanning  CSchumacher  HR  et al.  Multicentric reticulohistiocytosis. Arthritis Rheum 2000;43 (4) 930- 938
PubMed
Liang  GCGranston  AS Complete remission of multicentric reticulohistiocytosis with combination therapy of steroid, cyclophosphamide, and low-dose pulse methotrexate: case report, review of the literature, and proposal for treatment. Arthritis Rheum 1996;39 (1) 171- 174
PubMed
Nakajima  YSato  KMorita  H  et al.  Severe progressive erosive arthritis in multicentric reticulohistiocytosis: possible involvement of cytokines in synovial proliferation. J Rheumatol 1992;19 (10) 1643- 1646
PubMed
Salisbury  JRHall  PAWilliams  HC  et al.  Multicentric reticulohistiocytosis: detailed immunophenotyping confirms macrophage origin. Am J Surg Pathol 1990;14 (7) 687- 693
PubMed
Zagala  AGuyot  ABensa  JC  et al.  Multicentric reticulohistiocytosis: a case with enhanced interleukin-1, prostaglandin E2 and interleukin-2 secretion. J Rheumatol 1988;15 (1) 136- 138
PubMed
Nakamura  HYoshino  SShiga  H  et al.  A case of spontaneous femoral neck fracture associated with multicentric reticulohistiocytosis: oversecretion of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha by affected synovial cells. Arthritis Rheum 1997;40 (12) 2266- 2270
PubMed
Bolognia  JLedJorizzo  JLedRapini  RPed  Dermatology.   St Louis, MO Mosby Year Book Inc2003;
Badgwell  CRosen  T Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol 2007;56 (1) 69- 83
PubMed
Heffernan  MPSmith  DI Adalimumab for treatment of cutaneous sarcoidosis. Arch Dermatol 2006;142 (1) 17- 19
PubMed
Hertl  MSHaendle  ISchuler  G  et al.  Rapid improvement of recalcitrant disseminated granuloma annulare upon treatment with the tumor necrosis factor-α inhibitor, infliximab. Br J Dermatol 2005;152 (3) 552- 555
PubMed
Shupack  JSiu  K Resolving granuloma annulare with etanercept. Arch Dermatol 2006;142 (3) 394- 395
PubMed
Kolde  GMuche  JMSchulze  P  et al.  Infliximab: a promising new treatment option for ulcerated necrobiosis lipoidica. Dermatology 2003;206 (2) 180- 181
PubMed
Matejicka  CMorgan  GJSchlegelmilch  JG Multicentric reticulohistiocytosis treated successfully with an antitumor necrosis factor agent: comment on the article by Gorman et al. Arthritis Rheum 2003;48 (3) 864- 866
PubMed
Kovach  BTCalamia  KTWalsh  JS  et al.  Treatment of multicentric reticulohistiocytosis with etanercept. Arch Dermatol 2004;140 (8) 919- 921
PubMed
Lee  MWLee  EJeong  WI  et al.  Successful treatment of multicentric reticulohistiocytosis with a combination of infliximab, prednisone, and methotrexate. Acta Derm Venereol 2004;84 (6) 478- 479
PubMed
Shannon  SESchumacher  RSelf  S  et al.  Multicentric reticulohistiocytosis responding to tumor necrosis factor-α inhibition in a renal transplant patient. J Rheumatol 2005;32 (3) 565- 567
PubMed
Sellam  JDeslandre  CJDubreuil  F  et al.  Refractory multicentric reticulohistiocytosis treated by infliximab: two cases. Clin Exp Rheumatol 2005;23 (1) 97- 99
PubMed
Lovelace  KLoyd  AAdelson  D  et al.  Etanercept and the treatment of multicentric reticulohistiocytosis. Arch Dermatol 2005;141 (9) 1167- 1168
PubMed
Ehlers  S Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis 2005;41 ((suppl 3)) S199- S203
PubMed
Haitz  KAKalb  RE Infliximab in the treatment of psoriasis in patients previously treated with etanercept. J Am Acad Dermatol 2007;57 (1) 120- 125
PubMed
Bongartz  TSutton  AJSweeting  MJ  et al.  Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infection and malignancies. JAMA 2006;295 (19) 2275- 2285
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Treatment regimen prior to our initial evaluation. At time point 0, we initiated infliximab therapy in place of etanercept therapy, while continuing methotrexate sodium, prednisone, and isoniazid therapies.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Clinical appearance on initial examination revealed a poikilodermatous patch on his right chest (A), as well as firm, flesh-colored to deeply erythematous papules and nodules on his hands, fingers (B), ears (C), nares (D), and oral mucosa.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Arthroscopic image of knee revealing significant articular destruction from multicentric reticulohistiocytosis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Skin biopsy specimen showing dermal infiltration with multinucleated giant cells with an amorphous, eosinophilic, “ground-glass”– appearing cytoplasm (hematoxylin-eosin, original magnifications ×100 [main] and ×600 [inset]).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Resolution of poikilodermatous patch on right chest after 3 infliximab infusions (A), and near complete resolution of cutaneous papules on fingers (B), ears (C), and nares (D) after 7 months of receiving infliximab, methotrexate sodium, and prednisone therapies.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Previous Reports of Therapeutic Success With Tumor Necrosis Factor (TNF) Inhibition in Multicentric Reticulohistiocytosis
Table Graphic Jump LocationTable 2. Previous Reports of Less Effective Therapy With Tumor Necrosis Factor (TNF) Inhibition in Multicentric Reticulohistiocytosis

References

Luz  FBGaspar  APKalil-Gaspar  N  et al.  Multicentric reticulohistiocytosis. J Eur Acad Dermatol Venereol 2001;15 (6) 524- 531
PubMed
Hiramanek  NKossard  SBarnetson  RS Multicentric reticulohistiocytosis presenting with a rash and arthralgia. Australas J Dermatol 2002;43 (2) 136- 139
PubMed
Hsiung  SHChan  EFElenitsas  R  et al.  Multicentric reticulohistiocytosis presenting with clinical features of dermatomyositis. J Am Acad Dermatol 2003;48 (2) ((suppl)) S11- S14
PubMed
Tajirian  ALMalik  MKRobinson-Bostom  L  et al.  Multicentric reticulohistiocytosis. Clin Dermatol 2006;24 (6) 486- 492
PubMed
Lesher  JLAllen  BS Multicentric reticulohistiocytosis. J Am Acad Dermatol 1984;11 (4, pt 2) 713- 723
PubMed
Kurzrock  RCohen  PR Cutaneous paraneoplastic syndromes in solid tumors. Am J Med 1995;99 (6) 662- 671
PubMed
Catterall  MDWhite  JE Multicentric reticulohistiocytosis and malignant disease. Br J Dermatol 1978;98 (2) 221- 224
PubMed
Gorman  JDDanning  CSchumacher  HR  et al.  Multicentric reticulohistiocytosis. Arthritis Rheum 2000;43 (4) 930- 938
PubMed
Liang  GCGranston  AS Complete remission of multicentric reticulohistiocytosis with combination therapy of steroid, cyclophosphamide, and low-dose pulse methotrexate: case report, review of the literature, and proposal for treatment. Arthritis Rheum 1996;39 (1) 171- 174
PubMed
Nakajima  YSato  KMorita  H  et al.  Severe progressive erosive arthritis in multicentric reticulohistiocytosis: possible involvement of cytokines in synovial proliferation. J Rheumatol 1992;19 (10) 1643- 1646
PubMed
Salisbury  JRHall  PAWilliams  HC  et al.  Multicentric reticulohistiocytosis: detailed immunophenotyping confirms macrophage origin. Am J Surg Pathol 1990;14 (7) 687- 693
PubMed
Zagala  AGuyot  ABensa  JC  et al.  Multicentric reticulohistiocytosis: a case with enhanced interleukin-1, prostaglandin E2 and interleukin-2 secretion. J Rheumatol 1988;15 (1) 136- 138
PubMed
Nakamura  HYoshino  SShiga  H  et al.  A case of spontaneous femoral neck fracture associated with multicentric reticulohistiocytosis: oversecretion of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha by affected synovial cells. Arthritis Rheum 1997;40 (12) 2266- 2270
PubMed
Bolognia  JLedJorizzo  JLedRapini  RPed  Dermatology.   St Louis, MO Mosby Year Book Inc2003;
Badgwell  CRosen  T Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol 2007;56 (1) 69- 83
PubMed
Heffernan  MPSmith  DI Adalimumab for treatment of cutaneous sarcoidosis. Arch Dermatol 2006;142 (1) 17- 19
PubMed
Hertl  MSHaendle  ISchuler  G  et al.  Rapid improvement of recalcitrant disseminated granuloma annulare upon treatment with the tumor necrosis factor-α inhibitor, infliximab. Br J Dermatol 2005;152 (3) 552- 555
PubMed
Shupack  JSiu  K Resolving granuloma annulare with etanercept. Arch Dermatol 2006;142 (3) 394- 395
PubMed
Kolde  GMuche  JMSchulze  P  et al.  Infliximab: a promising new treatment option for ulcerated necrobiosis lipoidica. Dermatology 2003;206 (2) 180- 181
PubMed
Matejicka  CMorgan  GJSchlegelmilch  JG Multicentric reticulohistiocytosis treated successfully with an antitumor necrosis factor agent: comment on the article by Gorman et al. Arthritis Rheum 2003;48 (3) 864- 866
PubMed
Kovach  BTCalamia  KTWalsh  JS  et al.  Treatment of multicentric reticulohistiocytosis with etanercept. Arch Dermatol 2004;140 (8) 919- 921
PubMed
Lee  MWLee  EJeong  WI  et al.  Successful treatment of multicentric reticulohistiocytosis with a combination of infliximab, prednisone, and methotrexate. Acta Derm Venereol 2004;84 (6) 478- 479
PubMed
Shannon  SESchumacher  RSelf  S  et al.  Multicentric reticulohistiocytosis responding to tumor necrosis factor-α inhibition in a renal transplant patient. J Rheumatol 2005;32 (3) 565- 567
PubMed
Sellam  JDeslandre  CJDubreuil  F  et al.  Refractory multicentric reticulohistiocytosis treated by infliximab: two cases. Clin Exp Rheumatol 2005;23 (1) 97- 99
PubMed
Lovelace  KLoyd  AAdelson  D  et al.  Etanercept and the treatment of multicentric reticulohistiocytosis. Arch Dermatol 2005;141 (9) 1167- 1168
PubMed
Ehlers  S Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis 2005;41 ((suppl 3)) S199- S203
PubMed
Haitz  KAKalb  RE Infliximab in the treatment of psoriasis in patients previously treated with etanercept. J Am Acad Dermatol 2007;57 (1) 120- 125
PubMed
Bongartz  TSutton  AJSweeting  MJ  et al.  Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infection and malignancies. JAMA 2006;295 (19) 2275- 2285
PubMed

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