Patient Presentation
A 49-year-old African-American male presented with a 2-year history of a diffuse skin eruption and severe arthritis. On presentation, he complained of pain in multiple symmetric joints, including his wrists, hands, knees and ankles and had difficulty walking secondary to this pain. He had a past medical history of schizophrenia and alcohol abuse. On physical examination, there were multiple reddish brown papulonodules on his face, ears, neck, chest, back, arms, hands and legs. Several papules were aligned along the periungual regions of his fingers symmetrically. X-rays revealed erosive arthritis of multiple joints. Laboratory investigations were within normal limits and rheumatoid factor was negative. Purified protein derivative (PPD) test was negative. CT scan of the chest, abdomen and pelvis was negative for lymphadenopathy, and there was no evidence of malignancy. A biopsy of a representative nodule was performed.
What is Your Diagnosis?
Diagnosis: Multicentric Reticulohistiocytosis
Multicentric Reticulohistiocytosis (MRH) is a non-Langerhans cell histiocytosis containing both cutaneous and systemic features. It is characterized by cutaneous and mucous membrane reticulohistiocytomas and severe arthropathy.
The term multicentric reticulohistiocytosis was introduced by Goltz and Laymon1 in 1954 to define cases of reticulohistiocytoses with both cutaneous and systemic manifestations.
WHO IS TYPICALLY AFFECTED AND HOW?
MRH is a rare multisystem disease that is seen predominantly in Caucasian adults, although it occurs in all races. It is two to three times more common in women and most frequently occurs in the fourth decade.2 It is extremely rare with fewer than 200 cases reported, with pediatric cases being exceptionally rare.3 There appears to be no geographic area of prevalence.
CLINICAL FEATURES
MRH has an insidious onset and manifests as a papulonodular eruption and symmetric inflammatory polyarthritis. These papulonodules tend to be acrally distributed, and the common sites are the head, hands, fingers, ears and articular regions of the limbs. They are spherical, non-tender papules and nodules with a reddish-brown color varying in size from a couple millimeters to several centimeters. The papules often occur along the periungual areas giving a characteristic “coral bead appearance”.3
Mucosal involvement, which can present as nodules or papules, occur in one-third of cases and often involves the tongue, buccal or nasal mucosa.4
There is a symmetrical involvement of the interphalangeal joints (distal interphalangeal joints most commonly), knees, shoulders, wrists, hips, ankles, feet, elbows, and vertebral and temporomandibular joints. The arthritis is destructive (arthritis mutilans) as it causes destruction to both the bone and cartilage and is very painful. The arthritis can also cause absorption and telescopic shortening of the digits.5 These manifestations can severely impair the patient’s ability to carry out functions of daily living such as walking, climbing and grasping objects.
Skin and joint symptoms dominate the entire picture as almost two-thirds of patients with this disease notice the arthritis first; one-fifth notice the skin nodules first; and in another one-fifth of patients, the skin and joint changes appear simultaneously.5
MRH has also been associated with hyperlipidemia, positive tuberculin test, systemic vasculitis and autoimmune diseases such as systemic sclerosis and Sjögren’s syndrome.5 Anemia and elevated erythrocyte sedimentation rates have been reported in half of the patients.3
There can be histiocytic involvement of the heart, eye, lungs, thyroid, liver, kidney, muscle, salivary gland and bone marrow. Myocardial involvement may be fatal. Patients may also get pathologic fractures, hypertension and hyperextensible joints.5 Up to 28% of MRH patients have reportedly had an internal malignancy with bronchial, breast, stomach and cervical carcinomas being the most common.3
Skin lesions usually appear before the diagnosis of the malignancy, but a synchronous manifestation of skin lesions and an underlying malignancy is uncommonly reported.2
Active disease often remits in about 8 years6, although patients are left with significant disability. The course of MRH is unpredictable; half of the patients will eventually suffer from a destructive arthritis.
HISTOPATHOLOGY OF MRH
The histologic examination of MRH demonstrates intradermal and synovial infiltrate of histiocytes and multinucleated giant cells. The epidermis is slightly atrophic. Histiocytes are both mononuclear and multinuclear with abundant eosinophilic, homogenous, and finely granular cytoplasm giving a “ground glass” appearance.5 The MRH histiocytes stain positively for lysozyme and a1-antitrypsin and also express CD68, CD11b, CD14 and HAM56.7,8
In addition to histiocytes, small numbers of lymphocytes are also found in the infiltrate. Immunohistochemical staining has revealed inflammatory cytokines including TNF-a, interleukin 1 b, and interleukin 12.8,9,10
HOW DOES MRH DEVELOP?
The pathogenesis of MRH is unknown. It could be an abnormal histiocytic response to various stimuli such as a mycobacterial infection. In one study, 56% of MRH patients had positive tuberculin skin tests, but there has been no confirmation of mycobacteria in the skin nodules.6 MRH has been reported to respond to antituberculous treatment. Others have related it to an immunological response to an underlying autoimmune (systemic sclerosis, Sjögren’s)5 or neoplastic disorder.3
DIAGNOSIS OF MRH
The morphology and localization of cutaneous nodules, the typical articular symptoms, and the radiographic findings (such as symmetrical involvement of the distal interphalangeal joints) are highly suggestive of MRH. However, histopathological examination of a nodule confirms the diagnosis.5
Non-specific laboratory findings are present in individual cases: anemia, elevated sedimentation rate, leukocytosis, eosinophilia, hypo- and hyper-cholesterolemia, hypergammaglobulinemia, and the presence of cold agglutinins and cryoglobulins.5 Therefore, a complete blood count with differential, chemistry panel, sedimentation rate, lipid panel, cryoglobulins, liver function tests and serum protein electrophoresis should be ordered on diagnosis.
There is a high index of suspicion for malignancy in MRH patients and yearly comprehensive history and physical examinations are mandatory. The patient should initially have a full radiological workup (including chest X-ray and full body CT scan) to rule out any internal malignancy. Subsequent radiological and laboratory tests may be performed as warranted.
CONDITIONS TO CONSIDER IN THE DIFFERENTIAL DIAGNOSIS OF MRH
The differential diagnoses that are important to consider when presented with MRH are the other histiocytoses, especially Rosai-Dorfman disease and generalized eruptive histiocytosis. Rosai-Dorfman disease presents with classic massive, painless bilateral cervical lymphadenopathy, and generalized eruptive histiocytosis has recurrent crops of papules.3 The joint involvement may resemble rheumatoid arthritis and psoriatic arthritis.2
MANAGING THIS CONDITION
There is no gold standard for the treatment of MRH. The treatment options are non-steroidal anti-inflammatory medications, prednisone, methotrexate, hydroxy-chloroquine, chlorambucil (Leukeran) and cyclophosphamide (Cytoxan, Neosar).3 However, traditional systemic therapy has not been very effective in managing this condition successfully.
Elevated levels of TNF-a have been found in the synovium of patients with MRH. This has lead to the use of anti-TNF agents (e.g. infliximab [Remicade], etanercept [Enbrel], adalimumab [Humira]) in this disorder.11,12 Several studies have demonstrated that combination regimens with etanercept and methotrexate result in good control of the disease.11,12
Our patient was discharged from the hospital on 60 mg of prednisone. Methotrexate was not started at that time since he admitted to drinking alcohol frequently. The patient was subsequently lost to follow-up and was seen by rheumatology 1 year later with worsening joint pain and increased skin lesions. Initially, he was placed on etanercept 25 mg SC twice weekly for 3 months, but did not show any improvement. An anti-TNF agent as opposed to a systemic medication was selected for this patient based on his previous drug abuse history and the side effects of chronic steroid use. Subsequently, he was seen by dermatology and was placed on 5 mg of prednisone and 80 mg SC adalimumab every 2 weeks. The patient tolerated the injections very well. He received the injections in clinic. In about 6 months, the patient’s arthritis was significantly better and he could walk without assistance. His papulonodules had also decreased in size. At this time the patient had also obtained housing in a nursing facility and had stopped all recreational drug abuse. He is now taking 40 mg adalimumab SC weekly, 10 mg methotrexate, 1 mg folic acid and 5 mg prednisone. The patient is doing much better, but his lesions have not yet completely resolved.
Adalimumab
Adalimumab (Humira) is a monoclonal fully human anti-TNF-a antibody that binds with high affinity to TNF-a. It is approved for treating rheumatoid arthritis both in combination with methotrexate and as monotherapy. It is given by subcutaneous injection at a dose of 40 mg every 2 weeks. By replacing murine with human elements, the production of antibodies that neutralize the adalimumab injections is reduced. Common side effects are injection site reactions, infections (opportunistic like fungi and tuberculosis), lymphoproliferative disease (non-Hodgkins and Hodgkins lymphoma), demyelinating disease (reactivation of multiple sclerosis and optic neuritis), SLE-like syndromes and aggravation of congestive cardiac failure.13 Adalimumab probably worked better than etanercept (Enbrel) in the patient discussed in this case because of the fact it is a fully human anti-TNF monoclonal antibody that binds both soluble and membrane-bound TNF as opposed to etanercept, which is a fusion protein made up of soluble TNF-a receptor fused to the Fc portion of IgG1 that binds only circulating TNF-a.11,12,13
Patient Presentation
A 49-year-old African-American male presented with a 2-year history of a diffuse skin eruption and severe arthritis. On presentation, he complained of pain in multiple symmetric joints, including his wrists, hands, knees and ankles and had difficulty walking secondary to this pain. He had a past medical history of schizophrenia and alcohol abuse. On physical examination, there were multiple reddish brown papulonodules on his face, ears, neck, chest, back, arms, hands and legs. Several papules were aligned along the periungual regions of his fingers symmetrically. X-rays revealed erosive arthritis of multiple joints. Laboratory investigations were within normal limits and rheumatoid factor was negative. Purified protein derivative (PPD) test was negative. CT scan of the chest, abdomen and pelvis was negative for lymphadenopathy, and there was no evidence of malignancy. A biopsy of a representative nodule was performed.
What is Your Diagnosis?
Diagnosis: Multicentric Reticulohistiocytosis
Multicentric Reticulohistiocytosis (MRH) is a non-Langerhans cell histiocytosis containing both cutaneous and systemic features. It is characterized by cutaneous and mucous membrane reticulohistiocytomas and severe arthropathy.
The term multicentric reticulohistiocytosis was introduced by Goltz and Laymon1 in 1954 to define cases of reticulohistiocytoses with both cutaneous and systemic manifestations.
WHO IS TYPICALLY AFFECTED AND HOW?
MRH is a rare multisystem disease that is seen predominantly in Caucasian adults, although it occurs in all races. It is two to three times more common in women and most frequently occurs in the fourth decade.2 It is extremely rare with fewer than 200 cases reported, with pediatric cases being exceptionally rare.3 There appears to be no geographic area of prevalence.
CLINICAL FEATURES
MRH has an insidious onset and manifests as a papulonodular eruption and symmetric inflammatory polyarthritis. These papulonodules tend to be acrally distributed, and the common sites are the head, hands, fingers, ears and articular regions of the limbs. They are spherical, non-tender papules and nodules with a reddish-brown color varying in size from a couple millimeters to several centimeters. The papules often occur along the periungual areas giving a characteristic “coral bead appearance”.3
Mucosal involvement, which can present as nodules or papules, occur in one-third of cases and often involves the tongue, buccal or nasal mucosa.4
There is a symmetrical involvement of the interphalangeal joints (distal interphalangeal joints most commonly), knees, shoulders, wrists, hips, ankles, feet, elbows, and vertebral and temporomandibular joints. The arthritis is destructive (arthritis mutilans) as it causes destruction to both the bone and cartilage and is very painful. The arthritis can also cause absorption and telescopic shortening of the digits.5 These manifestations can severely impair the patient’s ability to carry out functions of daily living such as walking, climbing and grasping objects.
Skin and joint symptoms dominate the entire picture as almost two-thirds of patients with this disease notice the arthritis first; one-fifth notice the skin nodules first; and in another one-fifth of patients, the skin and joint changes appear simultaneously.5
MRH has also been associated with hyperlipidemia, positive tuberculin test, systemic vasculitis and autoimmune diseases such as systemic sclerosis and Sjögren’s syndrome.5 Anemia and elevated erythrocyte sedimentation rates have been reported in half of the patients.3
There can be histiocytic involvement of the heart, eye, lungs, thyroid, liver, kidney, muscle, salivary gland and bone marrow. Myocardial involvement may be fatal. Patients may also get pathologic fractures, hypertension and hyperextensible joints.5 Up to 28% of MRH patients have reportedly had an internal malignancy with bronchial, breast, stomach and cervical carcinomas being the most common.3
Skin lesions usually appear before the diagnosis of the malignancy, but a synchronous manifestation of skin lesions and an underlying malignancy is uncommonly reported.2
Active disease often remits in about 8 years6, although patients are left with significant disability. The course of MRH is unpredictable; half of the patients will eventually suffer from a destructive arthritis.
HISTOPATHOLOGY OF MRH
The histologic examination of MRH demonstrates intradermal and synovial infiltrate of histiocytes and multinucleated giant cells. The epidermis is slightly atrophic. Histiocytes are both mononuclear and multinuclear with abundant eosinophilic, homogenous, and finely granular cytoplasm giving a “ground glass” appearance.5 The MRH histiocytes stain positively for lysozyme and a1-antitrypsin and also express CD68, CD11b, CD14 and HAM56.7,8
In addition to histiocytes, small numbers of lymphocytes are also found in the infiltrate. Immunohistochemical staining has revealed inflammatory cytokines including TNF-a, interleukin 1 b, and interleukin 12.8,9,10
HOW DOES MRH DEVELOP?
The pathogenesis of MRH is unknown. It could be an abnormal histiocytic response to various stimuli such as a mycobacterial infection. In one study, 56% of MRH patients had positive tuberculin skin tests, but there has been no confirmation of mycobacteria in the skin nodules.6 MRH has been reported to respond to antituberculous treatment. Others have related it to an immunological response to an underlying autoimmune (systemic sclerosis, Sjögren’s)5 or neoplastic disorder.3
DIAGNOSIS OF MRH
The morphology and localization of cutaneous nodules, the typical articular symptoms, and the radiographic findings (such as symmetrical involvement of the distal interphalangeal joints) are highly suggestive of MRH. However, histopathological examination of a nodule confirms the diagnosis.5
Non-specific laboratory findings are present in individual cases: anemia, elevated sedimentation rate, leukocytosis, eosinophilia, hypo- and hyper-cholesterolemia, hypergammaglobulinemia, and the presence of cold agglutinins and cryoglobulins.5 Therefore, a complete blood count with differential, chemistry panel, sedimentation rate, lipid panel, cryoglobulins, liver function tests and serum protein electrophoresis should be ordered on diagnosis.
There is a high index of suspicion for malignancy in MRH patients and yearly comprehensive history and physical examinations are mandatory. The patient should initially have a full radiological workup (including chest X-ray and full body CT scan) to rule out any internal malignancy. Subsequent radiological and laboratory tests may be performed as warranted.
CONDITIONS TO CONSIDER IN THE DIFFERENTIAL DIAGNOSIS OF MRH
The differential diagnoses that are important to consider when presented with MRH are the other histiocytoses, especially Rosai-Dorfman disease and generalized eruptive histiocytosis. Rosai-Dorfman disease presents with classic massive, painless bilateral cervical lymphadenopathy, and generalized eruptive histiocytosis has recurrent crops of papules.3 The joint involvement may resemble rheumatoid arthritis and psoriatic arthritis.2
MANAGING THIS CONDITION
There is no gold standard for the treatment of MRH. The treatment options are non-steroidal anti-inflammatory medications, prednisone, methotrexate, hydroxy-chloroquine, chlorambucil (Leukeran) and cyclophosphamide (Cytoxan, Neosar).3 However, traditional systemic therapy has not been very effective in managing this condition successfully.
Elevated levels of TNF-a have been found in the synovium of patients with MRH. This has lead to the use of anti-TNF agents (e.g. infliximab [Remicade], etanercept [Enbrel], adalimumab [Humira]) in this disorder.11,12 Several studies have demonstrated that combination regimens with etanercept and methotrexate result in good control of the disease.11,12
Our patient was discharged from the hospital on 60 mg of prednisone. Methotrexate was not started at that time since he admitted to drinking alcohol frequently. The patient was subsequently lost to follow-up and was seen by rheumatology 1 year later with worsening joint pain and increased skin lesions. Initially, he was placed on etanercept 25 mg SC twice weekly for 3 months, but did not show any improvement. An anti-TNF agent as opposed to a systemic medication was selected for this patient based on his previous drug abuse history and the side effects of chronic steroid use. Subsequently, he was seen by dermatology and was placed on 5 mg of prednisone and 80 mg SC adalimumab every 2 weeks. The patient tolerated the injections very well. He received the injections in clinic. In about 6 months, the patient’s arthritis was significantly better and he could walk without assistance. His papulonodules had also decreased in size. At this time the patient had also obtained housing in a nursing facility and had stopped all recreational drug abuse. He is now taking 40 mg adalimumab SC weekly, 10 mg methotrexate, 1 mg folic acid and 5 mg prednisone. The patient is doing much better, but his lesions have not yet completely resolved.
Adalimumab
Adalimumab (Humira) is a monoclonal fully human anti-TNF-a antibody that binds with high affinity to TNF-a. It is approved for treating rheumatoid arthritis both in combination with methotrexate and as monotherapy. It is given by subcutaneous injection at a dose of 40 mg every 2 weeks. By replacing murine with human elements, the production of antibodies that neutralize the adalimumab injections is reduced. Common side effects are injection site reactions, infections (opportunistic like fungi and tuberculosis), lymphoproliferative disease (non-Hodgkins and Hodgkins lymphoma), demyelinating disease (reactivation of multiple sclerosis and optic neuritis), SLE-like syndromes and aggravation of congestive cardiac failure.13 Adalimumab probably worked better than etanercept (Enbrel) in the patient discussed in this case because of the fact it is a fully human anti-TNF monoclonal antibody that binds both soluble and membrane-bound TNF as opposed to etanercept, which is a fusion protein made up of soluble TNF-a receptor fused to the Fc portion of IgG1 that binds only circulating TNF-a.11,12,13
Patient Presentation
A 49-year-old African-American male presented with a 2-year history of a diffuse skin eruption and severe arthritis. On presentation, he complained of pain in multiple symmetric joints, including his wrists, hands, knees and ankles and had difficulty walking secondary to this pain. He had a past medical history of schizophrenia and alcohol abuse. On physical examination, there were multiple reddish brown papulonodules on his face, ears, neck, chest, back, arms, hands and legs. Several papules were aligned along the periungual regions of his fingers symmetrically. X-rays revealed erosive arthritis of multiple joints. Laboratory investigations were within normal limits and rheumatoid factor was negative. Purified protein derivative (PPD) test was negative. CT scan of the chest, abdomen and pelvis was negative for lymphadenopathy, and there was no evidence of malignancy. A biopsy of a representative nodule was performed.
What is Your Diagnosis?
Diagnosis: Multicentric Reticulohistiocytosis
Multicentric Reticulohistiocytosis (MRH) is a non-Langerhans cell histiocytosis containing both cutaneous and systemic features. It is characterized by cutaneous and mucous membrane reticulohistiocytomas and severe arthropathy.
The term multicentric reticulohistiocytosis was introduced by Goltz and Laymon1 in 1954 to define cases of reticulohistiocytoses with both cutaneous and systemic manifestations.
WHO IS TYPICALLY AFFECTED AND HOW?
MRH is a rare multisystem disease that is seen predominantly in Caucasian adults, although it occurs in all races. It is two to three times more common in women and most frequently occurs in the fourth decade.2 It is extremely rare with fewer than 200 cases reported, with pediatric cases being exceptionally rare.3 There appears to be no geographic area of prevalence.
CLINICAL FEATURES
MRH has an insidious onset and manifests as a papulonodular eruption and symmetric inflammatory polyarthritis. These papulonodules tend to be acrally distributed, and the common sites are the head, hands, fingers, ears and articular regions of the limbs. They are spherical, non-tender papules and nodules with a reddish-brown color varying in size from a couple millimeters to several centimeters. The papules often occur along the periungual areas giving a characteristic “coral bead appearance”.3
Mucosal involvement, which can present as nodules or papules, occur in one-third of cases and often involves the tongue, buccal or nasal mucosa.4
There is a symmetrical involvement of the interphalangeal joints (distal interphalangeal joints most commonly), knees, shoulders, wrists, hips, ankles, feet, elbows, and vertebral and temporomandibular joints. The arthritis is destructive (arthritis mutilans) as it causes destruction to both the bone and cartilage and is very painful. The arthritis can also cause absorption and telescopic shortening of the digits.5 These manifestations can severely impair the patient’s ability to carry out functions of daily living such as walking, climbing and grasping objects.
Skin and joint symptoms dominate the entire picture as almost two-thirds of patients with this disease notice the arthritis first; one-fifth notice the skin nodules first; and in another one-fifth of patients, the skin and joint changes appear simultaneously.5
MRH has also been associated with hyperlipidemia, positive tuberculin test, systemic vasculitis and autoimmune diseases such as systemic sclerosis and Sjögren’s syndrome.5 Anemia and elevated erythrocyte sedimentation rates have been reported in half of the patients.3
There can be histiocytic involvement of the heart, eye, lungs, thyroid, liver, kidney, muscle, salivary gland and bone marrow. Myocardial involvement may be fatal. Patients may also get pathologic fractures, hypertension and hyperextensible joints.5 Up to 28% of MRH patients have reportedly had an internal malignancy with bronchial, breast, stomach and cervical carcinomas being the most common.3
Skin lesions usually appear before the diagnosis of the malignancy, but a synchronous manifestation of skin lesions and an underlying malignancy is uncommonly reported.2
Active disease often remits in about 8 years6, although patients are left with significant disability. The course of MRH is unpredictable; half of the patients will eventually suffer from a destructive arthritis.
HISTOPATHOLOGY OF MRH
The histologic examination of MRH demonstrates intradermal and synovial infiltrate of histiocytes and multinucleated giant cells. The epidermis is slightly atrophic. Histiocytes are both mononuclear and multinuclear with abundant eosinophilic, homogenous, and finely granular cytoplasm giving a “ground glass” appearance.5 The MRH histiocytes stain positively for lysozyme and a1-antitrypsin and also express CD68, CD11b, CD14 and HAM56.7,8
In addition to histiocytes, small numbers of lymphocytes are also found in the infiltrate. Immunohistochemical staining has revealed inflammatory cytokines including TNF-a, interleukin 1 b, and interleukin 12.8,9,10
HOW DOES MRH DEVELOP?
The pathogenesis of MRH is unknown. It could be an abnormal histiocytic response to various stimuli such as a mycobacterial infection. In one study, 56% of MRH patients had positive tuberculin skin tests, but there has been no confirmation of mycobacteria in the skin nodules.6 MRH has been reported to respond to antituberculous treatment. Others have related it to an immunological response to an underlying autoimmune (systemic sclerosis, Sjögren’s)5 or neoplastic disorder.3
DIAGNOSIS OF MRH
The morphology and localization of cutaneous nodules, the typical articular symptoms, and the radiographic findings (such as symmetrical involvement of the distal interphalangeal joints) are highly suggestive of MRH. However, histopathological examination of a nodule confirms the diagnosis.5
Non-specific laboratory findings are present in individual cases: anemia, elevated sedimentation rate, leukocytosis, eosinophilia, hypo- and hyper-cholesterolemia, hypergammaglobulinemia, and the presence of cold agglutinins and cryoglobulins.5 Therefore, a complete blood count with differential, chemistry panel, sedimentation rate, lipid panel, cryoglobulins, liver function tests and serum protein electrophoresis should be ordered on diagnosis.
There is a high index of suspicion for malignancy in MRH patients and yearly comprehensive history and physical examinations are mandatory. The patient should initially have a full radiological workup (including chest X-ray and full body CT scan) to rule out any internal malignancy. Subsequent radiological and laboratory tests may be performed as warranted.
CONDITIONS TO CONSIDER IN THE DIFFERENTIAL DIAGNOSIS OF MRH
The differential diagnoses that are important to consider when presented with MRH are the other histiocytoses, especially Rosai-Dorfman disease and generalized eruptive histiocytosis. Rosai-Dorfman disease presents with classic massive, painless bilateral cervical lymphadenopathy, and generalized eruptive histiocytosis has recurrent crops of papules.3 The joint involvement may resemble rheumatoid arthritis and psoriatic arthritis.2
MANAGING THIS CONDITION
There is no gold standard for the treatment of MRH. The treatment options are non-steroidal anti-inflammatory medications, prednisone, methotrexate, hydroxy-chloroquine, chlorambucil (Leukeran) and cyclophosphamide (Cytoxan, Neosar).3 However, traditional systemic therapy has not been very effective in managing this condition successfully.
Elevated levels of TNF-a have been found in the synovium of patients with MRH. This has lead to the use of anti-TNF agents (e.g. infliximab [Remicade], etanercept [Enbrel], adalimumab [Humira]) in this disorder.11,12 Several studies have demonstrated that combination regimens with etanercept and methotrexate result in good control of the disease.11,12
Our patient was discharged from the hospital on 60 mg of prednisone. Methotrexate was not started at that time since he admitted to drinking alcohol frequently. The patient was subsequently lost to follow-up and was seen by rheumatology 1 year later with worsening joint pain and increased skin lesions. Initially, he was placed on etanercept 25 mg SC twice weekly for 3 months, but did not show any improvement. An anti-TNF agent as opposed to a systemic medication was selected for this patient based on his previous drug abuse history and the side effects of chronic steroid use. Subsequently, he was seen by dermatology and was placed on 5 mg of prednisone and 80 mg SC adalimumab every 2 weeks. The patient tolerated the injections very well. He received the injections in clinic. In about 6 months, the patient’s arthritis was significantly better and he could walk without assistance. His papulonodules had also decreased in size. At this time the patient had also obtained housing in a nursing facility and had stopped all recreational drug abuse. He is now taking 40 mg adalimumab SC weekly, 10 mg methotrexate, 1 mg folic acid and 5 mg prednisone. The patient is doing much better, but his lesions have not yet completely resolved.
Adalimumab
Adalimumab (Humira) is a monoclonal fully human anti-TNF-a antibody that binds with high affinity to TNF-a. It is approved for treating rheumatoid arthritis both in combination with methotrexate and as monotherapy. It is given by subcutaneous injection at a dose of 40 mg every 2 weeks. By replacing murine with human elements, the production of antibodies that neutralize the adalimumab injections is reduced. Common side effects are injection site reactions, infections (opportunistic like fungi and tuberculosis), lymphoproliferative disease (non-Hodgkins and Hodgkins lymphoma), demyelinating disease (reactivation of multiple sclerosis and optic neuritis), SLE-like syndromes and aggravation of congestive cardiac failure.13 Adalimumab probably worked better than etanercept (Enbrel) in the patient discussed in this case because of the fact it is a fully human anti-TNF monoclonal antibody that binds both soluble and membrane-bound TNF as opposed to etanercept, which is a fusion protein made up of soluble TNF-a receptor fused to the Fc portion of IgG1 that binds only circulating TNF-a.11,12,13
