Accepted Manuscript A missed opportunity: tophaceous gout Tal Gazitt, MD, MSc, Jenna Thomason, MD, MPH, Grant C. Hughes, MD PII:
S0002-9343(15)00174-6
DOI:
10.1016/j.amjmed.2015.01.039
Reference:
AJM 12889
To appear in:
The American Journal of Medicine
Received Date: 11 June 2014 Revised Date:
29 January 2015
Accepted Date: 29 January 2015
Please cite this article as: Gazitt T, Thomason J, Hughes GC, A missed opportunity: tophaceous gout, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.01.039. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 1 of 5 Manuscript title: A missed opportunity: tophaceous gout Manuscript type: Diagnostic Dilemma (DIS) Authors: 1)
Tal Gazitt, MD, MSc, Rheumatology Fellow, Division of Rheumatology,
2)
RI PT
University of Washington
Jenna Thomason, MD, MPH, Internal Medicine Resident, Department of
Medicine, University of Washington 3)
Grant C. Hughes, MD, Assistant Professor of Medicine and Rheumatology,
SC
University of Washington School of Medicine, Rheumatology Section Head,
M AN U
Harborview Medical Center
Corresponding author: Tal Gazitt, MD, MSc
Division of Rheumatology, University of Washington 1959 NE Pacific St, BB561 Box 356428
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Seattle, WA 98195-6428
Tel (206) 543-3414; Fax (206) 685-9397; E-mail: [email protected] All authors had access to the medical data reviewed in this manuscript and contributed to the writing of this manuscript.
EP
No grant funding was used in the preparation of this manuscript. Key words: chronic tophaceous gout, subcutaneous nodules, rheumatoid factor
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Running head: Erosive hand arthritis and serum RF Erosive arthritis, subcutaneous nodules and serum rheumatoid factor
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 2 of 5 Diagnostic Dilemma
A missed opportunity: tophaceous gout
RI PT
Aimee K. Zaas, MD, Section Editor
Tal Gazitt, MD, MSc,a Jenna Thomason, MD, MPH,b Grant C. Hughes, MDa,c
SC
Division of aRheumatology, bDepartment of Medicine, University of Washington School of
M AN U
Medicine and cDepartment of Rheumatology, Harborview Medical Center, Seattle, WA.
Requests for reprints should be addressed to Tal Gazitt, MD, MSc, Division of Rheumatology, University of Washington School of Medicine, 1959 NE Pacific Street, BB561 Box 356428, Seattle, WA, 98195-6428.
PRESENTATION
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E-mail address: [email protected]
Several features of one patient’s case belied the original diagnosis. A 70-year-old Filipino man
EP
presented to the clinic, complaining of subacute worsening of chronic hand pain. Two weeks prior, he experienced increasing pain and swelling of the metacarpophalangeal joints and both
AC C
wrists. Over the past several years, he had similar episodes, each lasting 2-3 weeks; shorter when he received oral nonsteroidal anti-inflammatory drugs or prednisone. Between these periods, minimal joint swelling and stiffness remained. Nevertheless, over time, he noted progressive deformity of his metacarpophalangeal joints. In addition, he reported occasional pain during use of the left shoulder and both knees. He denied fever, chills, rash, or neurologic problems. He had a history of hypertension, chronic renal insufficiency, and remote heavy alcohol use. His only medications were naproxen and acetaminophen.
ASSESSMENT
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 3 of 5 The patient appeared well. Cardiopulmonary, abdominal, and neurological examinations did not reveal significant abnormalities. A musculoskeletal examination identified mild swelling about the radiocarpal and metacarpophalangeal joints; bony hypertrophy of the first through third metacarpophalangeal joints of both hands, with ulnar deviation of the fingers on the right; bony
RI PT
hypertrophy of the proximal interphalangeal joints; boutonniere deformity of the left fifth finger; and bilateral thenar muscle wasting. He was unable to make a complete fist with his right hand due to decreased flexion of the metacarpophalangeal joints. Hard subcutaneous nodules were evident over the extensor surface of the right third metacarpophalangeal joint and over both
SC
olecranon processes. Both feet had hammertoe deformities. He had no knee effusions, rash, or nail dystrophy.
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Initial laboratory results included a serum C-reactive protein level of 91.5 mg/L (normal range, 0-10 mg/L) and a rheumatoid factor level of 191 U/mL (normal range, 0-13 U/mL). Serum anti–citrullinated protein antibodies, as measured by the anti-cyclic citrullinated antibody test, were undetectable. The patient’s estimated glomerular filtration rate was 40 mL/min (normal range, > 59 mL/min). Radiographs of his hands and wrists showed erosions of the right third metacarpal head, left distal radius and ulna, and left scaphoid bone, consistent with
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inflammatory arthritis (Figure). Radiographs of his feet demonstrated moderate osteoarthritic changes in his metatarsophalangeal joints (not shown). The patient was diagnosed with seropositive rheumatoid arthritis and treated with lowdose oral methotrexate, 7.5 mg weekly. Two weeks later, he returned with acute worsening of
EP
pain and swelling of his wrists, metacarpophalangeal joints, and subcutaneous nodules, as well as
AC C
new pain, swelling, and effusion in his knees and elbows.
DIAGNOSIS
At the time of his second presentation, the patient’s serum uric acid level was 6.8 mg/dL (normal range, 3.4-7 mg/dL). Arthrocentesis of the right knee yielded synovial fluid with numerous leukocytes and intra- and extracellular monosodium urate crystals. The diagnosis of rheumatoid arthritis was rescinded, and the patient was correctly diagnosed with gout. The differential diagnosis of erosive arthritis of the hands and wrists includes rheumatoid arthritis, gout, erosive osteoarthritis, and psoriatic arthritis, as well as rare conditions such as multicentric reticulohistiocytosis (Table 1). This case represents a missed opportunity to
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 4 of 5 diagnose chronic tophaceous gout, a common form of arthritis in adults. In this patient’s case, a diagnosis of psoriatic arthritis was reasonably excluded in the absence of psoriasis or fingernail abnormalities. Moreover, a diagnosis other than osteoarthritis was suggested by prominent involvement of the metacarpophalangeal joints and wrists. Both rheumatoid arthritis and gout
RI PT
can cause bony erosions and subcutaneous nodules.
However, several features of the initial presentation should have suggested a diagnosis of gout instead of rheumatoid arthritis, preventing the unnecessary trial of methotrexate. First, the patient offered a history of episodic arthritis punctuated by long relatively symptom-free
SC
periods—a pattern characteristic of gout but not rheumatoid arthritis. The pronounced asymmetry of joint involvement was another important clue; rheumatoid arthritis joint
M AN U
involvement is highly symmetric while that of gout is typically asymmetric. Rheumatoid nodules are fleshy, while this patient’s nodules were hard, more consistent with tophi, a word derived from tofus, the Latin word for stone. Finally, the likelihood of gout was heightened by the presence of several strong risk factors: chronic kidney disease, prior heavy alcohol use, and Filipino ancestry.1
The presence of rheumatoid factor and erosive hand arthritis is certainly consistent with a
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diagnosis of rheumatoid arthritis, but it is important to note that serum rheumatoid factor in the absence of serum anti–citrullinated protein antibodies is a nonspecific finding that can occur in various inflammatory conditions other than rheumatoid arthritis—including gout.2-4 Thus, the history, initial examination, and radiographic findings should have suggested a diagnosis of gout.
EP
Simple aspiration of synovial fluid, bursal fluid, or a nodule, followed by microscopic evaluation for monosodium urate crystals, could have confirmed the diagnosis.
AC C
It is important to remember that gout has both acute and chronic forms. Acute arthritis, for example, podagra, is the more widely recognized form. Untreated, gout can progress to chronic low-grade arthritis punctuated by acute flares. Frequently, this chronic polyarthritis form of gout, as seen in our patient, is accompanied by subcutaneous tophi and bony erosions.5 A chronic polyarthritis closely resembling rheumatoid arthritis occurs in about 5% of patients.2 In these cases, correct diagnosis relies on recognition of this form of gout and simple aspiration of a joint, bursa, or nodule.
MANAGEMENT
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 5 of 5 The patient was hospitalized for management of an acute polyarticular gout flare. Because of the number of joints involved, he was treated with high-dose oral glucocorticoids, but this failed to adequately control his symptoms. Use of colchicine or a nonsteroidal anti-inflammatory drug was avoided due to the patient’s renal insufficiency. Instead, he was treated with an interleukin-1
RI PT
antagonist—a promising new strategy for treating acute gout—with excellent results.6 When the patient returned to the clinic 2 weeks after hospital discharge, his acute joint symptoms had resolved. His serum uric acid level was 10.1 mg/dL, and he was started on uric acid-lowering
SC
therapy plus low-dose prednisone as prophylaxis against future gout attacks.
References
2014;66:337-343.
M AN U
1. Prasad P, Krishnan E. Filipino gout: a review. Arthritis Care Res (Hoboken).
2. Schapira D, Stahl S, Izhak OB, Balbir-Gurman A, Nahir AM. Chronic tophaceous gouty arthritis mimicking rheumatoid arthritis. Semin Arthritis Rheum. 1999;29:56-63. 3. Shmerling RH, Delbanco TL. The rheumatoid factor: an analysis of clinical utility. Am J Med. 1991;91:528-534.
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4. Talbott JH, Altman RD, Yü TF. Gouty arthritis masquerading as rheumatoid arthritis or vice versa. Semin Arthritis Rheum. 1978;8:77-114. 5. Richette P, Bardin T. Gout. Lancet. 2010;375:318-328. 6. Schlesinger N. Anti-interleukin-1 therapy in the management of gout. Curr Rheumatol
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EP
Rep. 2014;16:398.
Table 1. Diagnostic features of select causes of chronic erosive arthritis of the hands.
Figure. Radiographs of the patient’s hands and wrists showed prominent bony erosions (arrowheads).
ACCEPTED MANUSCRIPT
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EP
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M AN U
SC
RI PT
Table I. Diagnostic features of select causes of chronic, erosive hand arthritis Radiographic [7] Condition Clinical Laboratory -Asymmetric: any joints, but - Erosions: peri-articular or bone -MSU crystals in Gout DIP joints common in hands shaft, typically well-demarcated synovial/bursal fluid -Elevated serum uric -Hard, subcutaneous nodules with overhanging edges (tophi) -Soft tissue masses (tophi) acid -Episodic attacks or flarses -Highly symmetric: wrists, MCP -Erosions: typically peri-articular, -RF Rheumatoid and PIP joints poorly demarcated -ACPA arthritis -Spares DIP joints -Periarticular osteopenia -Fleshy, subcutaneous nodules -Symmetric: DIP and PIP joints -Erosions: central N/A Erosive -Spares MCP joints and wrists -“Gull-wing” joint space osteoarthritis -Prominent osteophytes (e.g., narrowing (esp. DIP joints) Heberden’s nodes) -prominent osteophytosis of PIP and DIP joints -Psoriasis -Erosions: peri-articular, may be -Usually RF negative Psoriatic -Fingernail pitting/dystrophy well- or poorly demarcated arthritis -Many patterns of joint -Osteolysis involvement -Periosteal bone reaction Abbreviations: DIP, distal interphalangeal; MSU, monosodium urate; MCP, metacarpophalangeal; PIP, proximal interphalangeal; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0002-9343(15)00174-6
DOI:
10.1016/j.amjmed.2015.01.039
Reference:
AJM 12889
To appear in:
The American Journal of Medicine
Received Date: 11 June 2014 Revised Date:
29 January 2015
Accepted Date: 29 January 2015
Please cite this article as: Gazitt T, Thomason J, Hughes GC, A missed opportunity: tophaceous gout, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.01.039. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 1 of 5 Manuscript title: A missed opportunity: tophaceous gout Manuscript type: Diagnostic Dilemma (DIS) Authors: 1)
Tal Gazitt, MD, MSc, Rheumatology Fellow, Division of Rheumatology,
2)
RI PT
University of Washington
Jenna Thomason, MD, MPH, Internal Medicine Resident, Department of
Medicine, University of Washington 3)
Grant C. Hughes, MD, Assistant Professor of Medicine and Rheumatology,
SC
University of Washington School of Medicine, Rheumatology Section Head,
M AN U
Harborview Medical Center
Corresponding author: Tal Gazitt, MD, MSc
Division of Rheumatology, University of Washington 1959 NE Pacific St, BB561 Box 356428
TE D
Seattle, WA 98195-6428
Tel (206) 543-3414; Fax (206) 685-9397; E-mail: [email protected] All authors had access to the medical data reviewed in this manuscript and contributed to the writing of this manuscript.
EP
No grant funding was used in the preparation of this manuscript. Key words: chronic tophaceous gout, subcutaneous nodules, rheumatoid factor
AC C
Running head: Erosive hand arthritis and serum RF Erosive arthritis, subcutaneous nodules and serum rheumatoid factor
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 2 of 5 Diagnostic Dilemma
A missed opportunity: tophaceous gout
RI PT
Aimee K. Zaas, MD, Section Editor
Tal Gazitt, MD, MSc,a Jenna Thomason, MD, MPH,b Grant C. Hughes, MDa,c
SC
Division of aRheumatology, bDepartment of Medicine, University of Washington School of
M AN U
Medicine and cDepartment of Rheumatology, Harborview Medical Center, Seattle, WA.
Requests for reprints should be addressed to Tal Gazitt, MD, MSc, Division of Rheumatology, University of Washington School of Medicine, 1959 NE Pacific Street, BB561 Box 356428, Seattle, WA, 98195-6428.
PRESENTATION
TE D
E-mail address: [email protected]
Several features of one patient’s case belied the original diagnosis. A 70-year-old Filipino man
EP
presented to the clinic, complaining of subacute worsening of chronic hand pain. Two weeks prior, he experienced increasing pain and swelling of the metacarpophalangeal joints and both
AC C
wrists. Over the past several years, he had similar episodes, each lasting 2-3 weeks; shorter when he received oral nonsteroidal anti-inflammatory drugs or prednisone. Between these periods, minimal joint swelling and stiffness remained. Nevertheless, over time, he noted progressive deformity of his metacarpophalangeal joints. In addition, he reported occasional pain during use of the left shoulder and both knees. He denied fever, chills, rash, or neurologic problems. He had a history of hypertension, chronic renal insufficiency, and remote heavy alcohol use. His only medications were naproxen and acetaminophen.
ASSESSMENT
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 3 of 5 The patient appeared well. Cardiopulmonary, abdominal, and neurological examinations did not reveal significant abnormalities. A musculoskeletal examination identified mild swelling about the radiocarpal and metacarpophalangeal joints; bony hypertrophy of the first through third metacarpophalangeal joints of both hands, with ulnar deviation of the fingers on the right; bony
RI PT
hypertrophy of the proximal interphalangeal joints; boutonniere deformity of the left fifth finger; and bilateral thenar muscle wasting. He was unable to make a complete fist with his right hand due to decreased flexion of the metacarpophalangeal joints. Hard subcutaneous nodules were evident over the extensor surface of the right third metacarpophalangeal joint and over both
SC
olecranon processes. Both feet had hammertoe deformities. He had no knee effusions, rash, or nail dystrophy.
M AN U
Initial laboratory results included a serum C-reactive protein level of 91.5 mg/L (normal range, 0-10 mg/L) and a rheumatoid factor level of 191 U/mL (normal range, 0-13 U/mL). Serum anti–citrullinated protein antibodies, as measured by the anti-cyclic citrullinated antibody test, were undetectable. The patient’s estimated glomerular filtration rate was 40 mL/min (normal range, > 59 mL/min). Radiographs of his hands and wrists showed erosions of the right third metacarpal head, left distal radius and ulna, and left scaphoid bone, consistent with
TE D
inflammatory arthritis (Figure). Radiographs of his feet demonstrated moderate osteoarthritic changes in his metatarsophalangeal joints (not shown). The patient was diagnosed with seropositive rheumatoid arthritis and treated with lowdose oral methotrexate, 7.5 mg weekly. Two weeks later, he returned with acute worsening of
EP
pain and swelling of his wrists, metacarpophalangeal joints, and subcutaneous nodules, as well as
AC C
new pain, swelling, and effusion in his knees and elbows.
DIAGNOSIS
At the time of his second presentation, the patient’s serum uric acid level was 6.8 mg/dL (normal range, 3.4-7 mg/dL). Arthrocentesis of the right knee yielded synovial fluid with numerous leukocytes and intra- and extracellular monosodium urate crystals. The diagnosis of rheumatoid arthritis was rescinded, and the patient was correctly diagnosed with gout. The differential diagnosis of erosive arthritis of the hands and wrists includes rheumatoid arthritis, gout, erosive osteoarthritis, and psoriatic arthritis, as well as rare conditions such as multicentric reticulohistiocytosis (Table 1). This case represents a missed opportunity to
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 4 of 5 diagnose chronic tophaceous gout, a common form of arthritis in adults. In this patient’s case, a diagnosis of psoriatic arthritis was reasonably excluded in the absence of psoriasis or fingernail abnormalities. Moreover, a diagnosis other than osteoarthritis was suggested by prominent involvement of the metacarpophalangeal joints and wrists. Both rheumatoid arthritis and gout
RI PT
can cause bony erosions and subcutaneous nodules.
However, several features of the initial presentation should have suggested a diagnosis of gout instead of rheumatoid arthritis, preventing the unnecessary trial of methotrexate. First, the patient offered a history of episodic arthritis punctuated by long relatively symptom-free
SC
periods—a pattern characteristic of gout but not rheumatoid arthritis. The pronounced asymmetry of joint involvement was another important clue; rheumatoid arthritis joint
M AN U
involvement is highly symmetric while that of gout is typically asymmetric. Rheumatoid nodules are fleshy, while this patient’s nodules were hard, more consistent with tophi, a word derived from tofus, the Latin word for stone. Finally, the likelihood of gout was heightened by the presence of several strong risk factors: chronic kidney disease, prior heavy alcohol use, and Filipino ancestry.1
The presence of rheumatoid factor and erosive hand arthritis is certainly consistent with a
TE D
diagnosis of rheumatoid arthritis, but it is important to note that serum rheumatoid factor in the absence of serum anti–citrullinated protein antibodies is a nonspecific finding that can occur in various inflammatory conditions other than rheumatoid arthritis—including gout.2-4 Thus, the history, initial examination, and radiographic findings should have suggested a diagnosis of gout.
EP
Simple aspiration of synovial fluid, bursal fluid, or a nodule, followed by microscopic evaluation for monosodium urate crystals, could have confirmed the diagnosis.
AC C
It is important to remember that gout has both acute and chronic forms. Acute arthritis, for example, podagra, is the more widely recognized form. Untreated, gout can progress to chronic low-grade arthritis punctuated by acute flares. Frequently, this chronic polyarthritis form of gout, as seen in our patient, is accompanied by subcutaneous tophi and bony erosions.5 A chronic polyarthritis closely resembling rheumatoid arthritis occurs in about 5% of patients.2 In these cases, correct diagnosis relies on recognition of this form of gout and simple aspiration of a joint, bursa, or nodule.
MANAGEMENT
ACCEPTED MANUSCRIPT 14-869GazittCHS, Page 5 of 5 The patient was hospitalized for management of an acute polyarticular gout flare. Because of the number of joints involved, he was treated with high-dose oral glucocorticoids, but this failed to adequately control his symptoms. Use of colchicine or a nonsteroidal anti-inflammatory drug was avoided due to the patient’s renal insufficiency. Instead, he was treated with an interleukin-1
RI PT
antagonist—a promising new strategy for treating acute gout—with excellent results.6 When the patient returned to the clinic 2 weeks after hospital discharge, his acute joint symptoms had resolved. His serum uric acid level was 10.1 mg/dL, and he was started on uric acid-lowering
SC
therapy plus low-dose prednisone as prophylaxis against future gout attacks.
References
2014;66:337-343.
M AN U
1. Prasad P, Krishnan E. Filipino gout: a review. Arthritis Care Res (Hoboken).
2. Schapira D, Stahl S, Izhak OB, Balbir-Gurman A, Nahir AM. Chronic tophaceous gouty arthritis mimicking rheumatoid arthritis. Semin Arthritis Rheum. 1999;29:56-63. 3. Shmerling RH, Delbanco TL. The rheumatoid factor: an analysis of clinical utility. Am J Med. 1991;91:528-534.
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4. Talbott JH, Altman RD, Yü TF. Gouty arthritis masquerading as rheumatoid arthritis or vice versa. Semin Arthritis Rheum. 1978;8:77-114. 5. Richette P, Bardin T. Gout. Lancet. 2010;375:318-328. 6. Schlesinger N. Anti-interleukin-1 therapy in the management of gout. Curr Rheumatol
AC C
EP
Rep. 2014;16:398.
Table 1. Diagnostic features of select causes of chronic erosive arthritis of the hands.
Figure. Radiographs of the patient’s hands and wrists showed prominent bony erosions (arrowheads).
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Table I. Diagnostic features of select causes of chronic, erosive hand arthritis Radiographic [7] Condition Clinical Laboratory -Asymmetric: any joints, but - Erosions: peri-articular or bone -MSU crystals in Gout DIP joints common in hands shaft, typically well-demarcated synovial/bursal fluid -Elevated serum uric -Hard, subcutaneous nodules with overhanging edges (tophi) -Soft tissue masses (tophi) acid -Episodic attacks or flarses -Highly symmetric: wrists, MCP -Erosions: typically peri-articular, -RF Rheumatoid and PIP joints poorly demarcated -ACPA arthritis -Spares DIP joints -Periarticular osteopenia -Fleshy, subcutaneous nodules -Symmetric: DIP and PIP joints -Erosions: central N/A Erosive -Spares MCP joints and wrists -“Gull-wing” joint space osteoarthritis -Prominent osteophytes (e.g., narrowing (esp. DIP joints) Heberden’s nodes) -prominent osteophytosis of PIP and DIP joints -Psoriasis -Erosions: peri-articular, may be -Usually RF negative Psoriatic -Fingernail pitting/dystrophy well- or poorly demarcated arthritis -Many patterns of joint -Osteolysis involvement -Periosteal bone reaction Abbreviations: DIP, distal interphalangeal; MSU, monosodium urate; MCP, metacarpophalangeal; PIP, proximal interphalangeal; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies
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EP
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M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
