Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.¹ Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.² Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.³ The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.¹ Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.² Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.³ The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.¹ Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.² Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.³ The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.

Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.

Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.

Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.

Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.

Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.

Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation. 

Click on the PDF icon at the top of this introduction to read the full article.

Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.

Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.

Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.

Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.

Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.

Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.

Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation. 

Click on the PDF icon at the top of this introduction to read the full article.

Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.

Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.

Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.

Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.

Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.

Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.

Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation. 

Click on the PDF icon at the top of this introduction to read the full article.

Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).

Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.

Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”

Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.

Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.

Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.

Funding Janssen Research & Development

Click on the PDF icon at the top of this introduction to read the full article.

Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).

Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.

Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”

Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.

Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.

Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.

Funding Janssen Research & Development

Click on the PDF icon at the top of this introduction to read the full article.

Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).

Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.

Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”

Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.

Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.

Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.

Funding Janssen Research & Development

Click on the PDF icon at the top of this introduction to read the full article.

Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.

Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.

Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.

Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.

Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).

Funding Reich Endowment for the Care of the Whole Patient
 

Click on the PDF icon at the top of this introduction to read the full article.
 

Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.

Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.

Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.

Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.

Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).

Funding Reich Endowment for the Care of the Whole Patient
 

Click on the PDF icon at the top of this introduction to read the full article.
 

Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.

Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.

Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.

Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.

Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).

Funding Reich Endowment for the Care of the Whole Patient
 

Click on the PDF icon at the top of this introduction to read the full article.
 

A 68-year-old Filipino man with a history of hypertension, type 2 diabetes, and osteoarthritis presented to the emergency department with a one-week history of increasing pain, swelling, erythema, and seepage of his right great toe. The patient denied paresthesias, fever, chills, night sweats, cough, dyspnea, or any change in his diet, medications (which included lisinopril, metformin, and acetaminophen as needed), or routine. Social history was negative for alcohol use and cigarette smoking.

He previously had similar symptoms in his right fourth toe that resulted in amputation. The patient was told at the time that he had a “bone infection” and amputation was necessary.

The patient was thin, alert, oriented, and in no acute distress. His vital signs and a cardiopulmonary exam were normal. The patient’s right great toe was tender to touch, with ulceration of the skin dorsally at the proximal nail fold. In addition, his toe was oozing a purulent, non-foul smelling discharge (FIGURE 1). Other pertinent findings included multiple enlarged joints on both hands with visible yellow-white subcutaneous nodules on the hands and dorsum of the forearm (FIGURE 2).

The patient’s white blood cell count was 10,800/mcL, C-reactive protein (CRP) was 18 mg/L, erythrocyte sedimentation rate (ESR) was 80 mm/hr, and uric acid was 12.5 mg/dL. His blood urea nitrogen was 52 mg/dL and creatinine was 2.5 mg/dL. A glycated hemoglobin test was 7.2%. A wound culture, aspirate from the dorsum of the toe, and x-ray were obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tophaceous gouty arthritis

The x-ray of the right great toe showed erosions of the metatarsophalangeal (MTP) joint (FIGURE 3). Given the patient’s age, underlying diabetes, skin ulceration, and elevation of CRP and ESR, the initial concern was for septic arthritis and osteomyelitis. However, the absence of leukocytosis and hyperglycemia argued against an infectious process.

The diagnosis of tophaceous gouty arthritis was confirmed by aspiration from the tophus, which demonstrated monosodium urate (MSU) crystals on polarized light microscopy. The patient presented with acute gout on the first right toe overlaying chronic tophaceous gout, complicated by renal failure.

Four phases. Gout progresses through 4 phases: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout (intervals between acute attacks), and chronic tophaceous gout.¹ Chronic tophaceous gout is characterized by tophi—collections of solid urate in connective tissues (from bone to bursa, tendons, ligaments, and entheses).² There are often multiple tophi and they may be calcified. An acute gouty attack is marked by a relatively sudden increase in pain and swelling, and may improve spontaneously over the course of 7 to 10 days.³

Gout is the most common form of inflammatory arthritis, with a prevalence in the United States of 3.9%.⁴The findings of several studies suggest that the prevalence and incidence of gout have risen in recent decades, which may be attributable to a growing aging population, the rise in obesity, increasing numbers of people who have other conditions such as heart disease, kidney disease, and/or diabetes, and the use of diuretics by individuals with cardiovascular disease.⁵

In a meta-analysis on gouty involvement of the first MTP joint, the occurrence of acute first MTP arthritis has been reported to be an independent predictor of MSU crystal presence in patients with gout.⁶ The presence of first MTP arthritis and the predilection for MSU deposition in the medial and dorsal aspects of the joint suggested an association, but no causation, between the 2 disease processes. The authors concluded that the distinction between osteoarthritis and gout as the cause of the joint damage is often difficult.

The diagnosis of gout may be made clinically based on established clinical criteria. The most commonly used are the 1977 American College of Rheumatology (ACR) criteria for the classification of acute arthritis of primary gout. (See “The 12 diagnostic criteria for gout.”⁷) However, in 2015, the ACR/European League Against Rheumatism (EULAR) published a new set of criteria that include the signs and symptoms of chronic gout, as well.⁸ (The ACR-EULAR Gout Classification Criteria Calculator may be accessed at http://goutclassificationcalculator.auckland.ac.nz/.)

Differential diagnosis includes trauma, septic and reactive arthritis

The differential diagnosis of acute gouty arthritis includes trauma, pseudogout (arthritis involving calcium pyrophosphate dehydrate), septic arthritis, reactive arthritis, post-streptococcal arthritis, and Lyme disease.

Trauma with a resulting acute or stress fracture can be determined by x-ray or magnetic resonance imaging (MRI).

Pseudogout requires aspiration of fluid and examination for calcium pyrophosphate crystals under polarizing microscopy.⁹

Septic arthritis may present in a similar manner to other causes of acute arthritis. Therefore, arthrocentesis is needed to identify the causative infectious agent.¹⁰ Septic arthritis was considered in our patient, given his age, history of diabetes mellitus, and finding of skin ulceration over the toe. However, our patient did not have systemic symptoms, and the joint aspiration did not show the presence of bacteria.

Reactive arthritis typically presents with inflammation of the ligaments and tendons at their sites of insertion into the bone, and can affect other areas of the body, such as the genitourinary and ocular systems.¹¹

Post-streptococcal arthritis (aka acute rheumatic fever [ARF]) and Lyme disease can also present with joint complaints. The arthritis in ARF is usually migratory and involves several joints. Fever, rash, and a history of group A streptococcal infection are also diagnostic features.¹² History of travel to an endemic area or seasonal exposure would further differentiate Lyme disease from other causes of arthritis.

Further inquiry during the patient’s hospitalization revealed that he ate a lot of seafood and organ meat.

Deciding on a course of treatment

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids.¹³ Various NSAIDs have been studied in the treatment of acute gout, but none showed absolute superiority over others. One option is naproxen 500 mg twice daily, but the choice of NSAID is mainly based on the adverse reaction profile and the physician’s preference.

Due to frequent gastrointestinal adverse effects and the concern for toxicity and drug interactions, colchicine and corticosteroids are not typically the first-line agents for acute gout treatment. Patients with frequent recurrent gouty attacks require urate-lowering therapies, such as allopurinol or probenecid. Other indications for urate-lowering therapies include evidence of tophaceous deposits in joints and soft tissues and gouty arthropathy.

Our patient’s renal failure was likely chronic, secondary to his untreated tophaceous gouty disease. Because his creatinine clearance was between 30 and 60 mL/min per 1.73 m², he was not treated with NSAIDs, but with colchicine 1.2 mg for his initial flare, followed with a single dose of 0.6 mg in one hour. The patient had dramatic improvement of his pain the following day.

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids.

Patient education on chronic gout was also provided. We specifically discussed the patient’s dietary habits with him, advising him to minimize his intake of seafood, animal organs, and red meat products, which are high in purines. The patient was also told that he would need to start urate-lowering therapy to prevent recurrent gouty attacks and further complications from gout.

CORRESPONDENCE
Joseph Huang, MD, Fort Belvoir Community Hospital, Family Medicine Clinic, 1st Floor Eagle Pavilion, 9300 Dewitt Loop, Fort Belvoir, VA 22060; [email protected].

A 68-year-old Filipino man with a history of hypertension, type 2 diabetes, and osteoarthritis presented to the emergency department with a one-week history of increasing pain, swelling, erythema, and seepage of his right great toe. The patient denied paresthesias, fever, chills, night sweats, cough, dyspnea, or any change in his diet, medications (which included lisinopril, metformin, and acetaminophen as needed), or routine. Social history was negative for alcohol use and cigarette smoking.

He previously had similar symptoms in his right fourth toe that resulted in amputation. The patient was told at the time that he had a “bone infection” and amputation was necessary.

The patient was thin, alert, oriented, and in no acute distress. His vital signs and a cardiopulmonary exam were normal. The patient’s right great toe was tender to touch, with ulceration of the skin dorsally at the proximal nail fold. In addition, his toe was oozing a purulent, non-foul smelling discharge (FIGURE 1). Other pertinent findings included multiple enlarged joints on both hands with visible yellow-white subcutaneous nodules on the hands and dorsum of the forearm (FIGURE 2).

The patient’s white blood cell count was 10,800/mcL, C-reactive protein (CRP) was 18 mg/L, erythrocyte sedimentation rate (ESR) was 80 mm/hr, and uric acid was 12.5 mg/dL. His blood urea nitrogen was 52 mg/dL and creatinine was 2.5 mg/dL. A glycated hemoglobin test was 7.2%. A wound culture, aspirate from the dorsum of the toe, and x-ray were obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tophaceous gouty arthritis

The x-ray of the right great toe showed erosions of the metatarsophalangeal (MTP) joint (FIGURE 3). Given the patient’s age, underlying diabetes, skin ulceration, and elevation of CRP and ESR, the initial concern was for septic arthritis and osteomyelitis. However, the absence of leukocytosis and hyperglycemia argued against an infectious process.

The diagnosis of tophaceous gouty arthritis was confirmed by aspiration from the tophus, which demonstrated monosodium urate (MSU) crystals on polarized light microscopy. The patient presented with acute gout on the first right toe overlaying chronic tophaceous gout, complicated by renal failure.

Four phases. Gout progresses through 4 phases: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout (intervals between acute attacks), and chronic tophaceous gout.¹ Chronic tophaceous gout is characterized by tophi—collections of solid urate in connective tissues (from bone to bursa, tendons, ligaments, and entheses).² There are often multiple tophi and they may be calcified. An acute gouty attack is marked by a relatively sudden increase in pain and swelling, and may improve spontaneously over the course of 7 to 10 days.³

Gout is the most common form of inflammatory arthritis, with a prevalence in the United States of 3.9%.⁴The findings of several studies suggest that the prevalence and incidence of gout have risen in recent decades, which may be attributable to a growing aging population, the rise in obesity, increasing numbers of people who have other conditions such as heart disease, kidney disease, and/or diabetes, and the use of diuretics by individuals with cardiovascular disease.⁵

In a meta-analysis on gouty involvement of the first MTP joint, the occurrence of acute first MTP arthritis has been reported to be an independent predictor of MSU crystal presence in patients with gout.⁶ The presence of first MTP arthritis and the predilection for MSU deposition in the medial and dorsal aspects of the joint suggested an association, but no causation, between the 2 disease processes. The authors concluded that the distinction between osteoarthritis and gout as the cause of the joint damage is often difficult.

The diagnosis of gout may be made clinically based on established clinical criteria. The most commonly used are the 1977 American College of Rheumatology (ACR) criteria for the classification of acute arthritis of primary gout. (See “The 12 diagnostic criteria for gout.”⁷) However, in 2015, the ACR/European League Against Rheumatism (EULAR) published a new set of criteria that include the signs and symptoms of chronic gout, as well.⁸ (The ACR-EULAR Gout Classification Criteria Calculator may be accessed at http://goutclassificationcalculator.auckland.ac.nz/.)

Differential diagnosis includes trauma, septic and reactive arthritis

The differential diagnosis of acute gouty arthritis includes trauma, pseudogout (arthritis involving calcium pyrophosphate dehydrate), septic arthritis, reactive arthritis, post-streptococcal arthritis, and Lyme disease.

Trauma with a resulting acute or stress fracture can be determined by x-ray or magnetic resonance imaging (MRI).

Pseudogout requires aspiration of fluid and examination for calcium pyrophosphate crystals under polarizing microscopy.⁹

Septic arthritis may present in a similar manner to other causes of acute arthritis. Therefore, arthrocentesis is needed to identify the causative infectious agent.¹⁰ Septic arthritis was considered in our patient, given his age, history of diabetes mellitus, and finding of skin ulceration over the toe. However, our patient did not have systemic symptoms, and the joint aspiration did not show the presence of bacteria.

Reactive arthritis typically presents with inflammation of the ligaments and tendons at their sites of insertion into the bone, and can affect other areas of the body, such as the genitourinary and ocular systems.¹¹

Post-streptococcal arthritis (aka acute rheumatic fever [ARF]) and Lyme disease can also present with joint complaints. The arthritis in ARF is usually migratory and involves several joints. Fever, rash, and a history of group A streptococcal infection are also diagnostic features.¹² History of travel to an endemic area or seasonal exposure would further differentiate Lyme disease from other causes of arthritis.

Further inquiry during the patient’s hospitalization revealed that he ate a lot of seafood and organ meat.

Deciding on a course of treatment

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids.¹³ Various NSAIDs have been studied in the treatment of acute gout, but none showed absolute superiority over others. One option is naproxen 500 mg twice daily, but the choice of NSAID is mainly based on the adverse reaction profile and the physician’s preference.

Due to frequent gastrointestinal adverse effects and the concern for toxicity and drug interactions, colchicine and corticosteroids are not typically the first-line agents for acute gout treatment. Patients with frequent recurrent gouty attacks require urate-lowering therapies, such as allopurinol or probenecid. Other indications for urate-lowering therapies include evidence of tophaceous deposits in joints and soft tissues and gouty arthropathy.

Our patient’s renal failure was likely chronic, secondary to his untreated tophaceous gouty disease. Because his creatinine clearance was between 30 and 60 mL/min per 1.73 m², he was not treated with NSAIDs, but with colchicine 1.2 mg for his initial flare, followed with a single dose of 0.6 mg in one hour. The patient had dramatic improvement of his pain the following day.

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids.

Patient education on chronic gout was also provided. We specifically discussed the patient’s dietary habits with him, advising him to minimize his intake of seafood, animal organs, and red meat products, which are high in purines. The patient was also told that he would need to start urate-lowering therapy to prevent recurrent gouty attacks and further complications from gout.

CORRESPONDENCE
Joseph Huang, MD, Fort Belvoir Community Hospital, Family Medicine Clinic, 1st Floor Eagle Pavilion, 9300 Dewitt Loop, Fort Belvoir, VA 22060; [email protected].

A 68-year-old Filipino man with a history of hypertension, type 2 diabetes, and osteoarthritis presented to the emergency department with a one-week history of increasing pain, swelling, erythema, and seepage of his right great toe. The patient denied paresthesias, fever, chills, night sweats, cough, dyspnea, or any change in his diet, medications (which included lisinopril, metformin, and acetaminophen as needed), or routine. Social history was negative for alcohol use and cigarette smoking.

He previously had similar symptoms in his right fourth toe that resulted in amputation. The patient was told at the time that he had a “bone infection” and amputation was necessary.

The patient was thin, alert, oriented, and in no acute distress. His vital signs and a cardiopulmonary exam were normal. The patient’s right great toe was tender to touch, with ulceration of the skin dorsally at the proximal nail fold. In addition, his toe was oozing a purulent, non-foul smelling discharge (FIGURE 1). Other pertinent findings included multiple enlarged joints on both hands with visible yellow-white subcutaneous nodules on the hands and dorsum of the forearm (FIGURE 2).

The patient’s white blood cell count was 10,800/mcL, C-reactive protein (CRP) was 18 mg/L, erythrocyte sedimentation rate (ESR) was 80 mm/hr, and uric acid was 12.5 mg/dL. His blood urea nitrogen was 52 mg/dL and creatinine was 2.5 mg/dL. A glycated hemoglobin test was 7.2%. A wound culture, aspirate from the dorsum of the toe, and x-ray were obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tophaceous gouty arthritis

The x-ray of the right great toe showed erosions of the metatarsophalangeal (MTP) joint (FIGURE 3). Given the patient’s age, underlying diabetes, skin ulceration, and elevation of CRP and ESR, the initial concern was for septic arthritis and osteomyelitis. However, the absence of leukocytosis and hyperglycemia argued against an infectious process.

The diagnosis of tophaceous gouty arthritis was confirmed by aspiration from the tophus, which demonstrated monosodium urate (MSU) crystals on polarized light microscopy. The patient presented with acute gout on the first right toe overlaying chronic tophaceous gout, complicated by renal failure.

Four phases. Gout progresses through 4 phases: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout (intervals between acute attacks), and chronic tophaceous gout.¹ Chronic tophaceous gout is characterized by tophi—collections of solid urate in connective tissues (from bone to bursa, tendons, ligaments, and entheses).² There are often multiple tophi and they may be calcified. An acute gouty attack is marked by a relatively sudden increase in pain and swelling, and may improve spontaneously over the course of 7 to 10 days.³

Gout is the most common form of inflammatory arthritis, with a prevalence in the United States of 3.9%.⁴The findings of several studies suggest that the prevalence and incidence of gout have risen in recent decades, which may be attributable to a growing aging population, the rise in obesity, increasing numbers of people who have other conditions such as heart disease, kidney disease, and/or diabetes, and the use of diuretics by individuals with cardiovascular disease.⁵

In a meta-analysis on gouty involvement of the first MTP joint, the occurrence of acute first MTP arthritis has been reported to be an independent predictor of MSU crystal presence in patients with gout.⁶ The presence of first MTP arthritis and the predilection for MSU deposition in the medial and dorsal aspects of the joint suggested an association, but no causation, between the 2 disease processes. The authors concluded that the distinction between osteoarthritis and gout as the cause of the joint damage is often difficult.

The diagnosis of gout may be made clinically based on established clinical criteria. The most commonly used are the 1977 American College of Rheumatology (ACR) criteria for the classification of acute arthritis of primary gout. (See “The 12 diagnostic criteria for gout.”⁷) However, in 2015, the ACR/European League Against Rheumatism (EULAR) published a new set of criteria that include the signs and symptoms of chronic gout, as well.⁸ (The ACR-EULAR Gout Classification Criteria Calculator may be accessed at http://goutclassificationcalculator.auckland.ac.nz/.)

Differential diagnosis includes trauma, septic and reactive arthritis

The differential diagnosis of acute gouty arthritis includes trauma, pseudogout (arthritis involving calcium pyrophosphate dehydrate), septic arthritis, reactive arthritis, post-streptococcal arthritis, and Lyme disease.

Trauma with a resulting acute or stress fracture can be determined by x-ray or magnetic resonance imaging (MRI).

Pseudogout requires aspiration of fluid and examination for calcium pyrophosphate crystals under polarizing microscopy.⁹

Septic arthritis may present in a similar manner to other causes of acute arthritis. Therefore, arthrocentesis is needed to identify the causative infectious agent.¹⁰ Septic arthritis was considered in our patient, given his age, history of diabetes mellitus, and finding of skin ulceration over the toe. However, our patient did not have systemic symptoms, and the joint aspiration did not show the presence of bacteria.

Reactive arthritis typically presents with inflammation of the ligaments and tendons at their sites of insertion into the bone, and can affect other areas of the body, such as the genitourinary and ocular systems.¹¹

Post-streptococcal arthritis (aka acute rheumatic fever [ARF]) and Lyme disease can also present with joint complaints. The arthritis in ARF is usually migratory and involves several joints. Fever, rash, and a history of group A streptococcal infection are also diagnostic features.¹² History of travel to an endemic area or seasonal exposure would further differentiate Lyme disease from other causes of arthritis.

Further inquiry during the patient’s hospitalization revealed that he ate a lot of seafood and organ meat.

Deciding on a course of treatment

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids.¹³ Various NSAIDs have been studied in the treatment of acute gout, but none showed absolute superiority over others. One option is naproxen 500 mg twice daily, but the choice of NSAID is mainly based on the adverse reaction profile and the physician’s preference.

Due to frequent gastrointestinal adverse effects and the concern for toxicity and drug interactions, colchicine and corticosteroids are not typically the first-line agents for acute gout treatment. Patients with frequent recurrent gouty attacks require urate-lowering therapies, such as allopurinol or probenecid. Other indications for urate-lowering therapies include evidence of tophaceous deposits in joints and soft tissues and gouty arthropathy.

Our patient’s renal failure was likely chronic, secondary to his untreated tophaceous gouty disease. Because his creatinine clearance was between 30 and 60 mL/min per 1.73 m², he was not treated with NSAIDs, but with colchicine 1.2 mg for his initial flare, followed with a single dose of 0.6 mg in one hour. The patient had dramatic improvement of his pain the following day.

Initial treatment choices for acute gout include nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids.

Patient education on chronic gout was also provided. We specifically discussed the patient’s dietary habits with him, advising him to minimize his intake of seafood, animal organs, and red meat products, which are high in purines. The patient was also told that he would need to start urate-lowering therapy to prevent recurrent gouty attacks and further complications from gout.

CORRESPONDENCE
Joseph Huang, MD, Fort Belvoir Community Hospital, Family Medicine Clinic, 1st Floor Eagle Pavilion, 9300 Dewitt Loop, Fort Belvoir, VA 22060; [email protected].

Evidence summary

A 2013 Cochrane review of 17 RCTs with 2596 patients compared corticosteroids with placebo for treating bronchiolitis in children younger than 2 years.¹ The studies used dexamethasone, prednisolone, prednisone, and budesonide delivered by oral, inhaled, intravenous (IV), or intramuscular (IM) routes, ranging between a one-day dose to a 5-day taper. Doses ranged from 0.5 to 2 mg/kg/d for oral and parenteral routes and 0.2 to 1 mg for inhalation. Outcomes were rate of admissions at Days 1 and 7 from outpatient trials and length of stay among inpatients.

Investigators found no significant difference in admission rates at Day 1 and Day 7 between children treated with corticosteroids compared with placebo (Day 1: 8 trials, 1762 patients; relative risk [RR]=0.92; 95% confidence interval [CI], 0.78-1.1; Day 7: 5 trials, 1530 patients; RR=0.86; 95% CI, 0.70-1.1). Length of hospital stay didn’t differ between children treated with corticosteroids and children who received placebo (8 trials, 633 patients; mean difference= −0.18 days; 95% CI, −0.39 to 0.04).

Corticosteroid + epinephrine can lower hospital admissions

A 2009 multicenter, double-blind RCT with 800 patients (infants 6 weeks to 12 months of age with a first episode of bronchiolitis) that was included in the 2013 Cochrane review also compared the combination of epinephrine and corticosteroid with placebo and either agent alone.²

Infants were assigned to 4 groups: oral dexamethasone alone (1 mg/kg in the emergency room [ER] on Day 1, followed by 0.6 mg/kg daily for 5 days); nebulized epinephrine alone (2 treatments of 3 mL epinephrine 1:1000 solution); combined dexamethasone and epinephrine; and placebo. The primary outcome was hospital admission as long as 7 days after being seen in the ER.

Rates of admission were similar for the dexamethasone and placebo groups (25.6% vs 26.4%, respectively; RR=0.96; 95% CI, 0.69-1.3). The epinephrine group’s rate of admission was 23.7% (RR=0.88; CI, 0.63–1.23). Only the dexamethasone-epinephrine group had a lower rate of admission compared with placebo (17% vs 26%; RR=0.65; 95% CI, 0.45-0.95). The number needed to treat with dexamethasone-epinephrine to prevent one hospital admission was 11.

Review prompts revised recommendations

Based on the Cochrane review, the American Academy of Pediatrics (AAP) revised its evidence-based clinical practice guideline in 2014 to recommend that clinicians not administer systemic corticosteroids to infants with a diagnosis of bronchiolitis in any setting (evidence quality B, strong recommendation, based on results of multiple RCTs).³ The AAP advocates additional large trials to clarify whether combination therapy (corticosteroids plus agents with α or β agonist activity) is effective.

Evidence summary

A 2013 Cochrane review of 17 RCTs with 2596 patients compared corticosteroids with placebo for treating bronchiolitis in children younger than 2 years.¹ The studies used dexamethasone, prednisolone, prednisone, and budesonide delivered by oral, inhaled, intravenous (IV), or intramuscular (IM) routes, ranging between a one-day dose to a 5-day taper. Doses ranged from 0.5 to 2 mg/kg/d for oral and parenteral routes and 0.2 to 1 mg for inhalation. Outcomes were rate of admissions at Days 1 and 7 from outpatient trials and length of stay among inpatients.

Investigators found no significant difference in admission rates at Day 1 and Day 7 between children treated with corticosteroids compared with placebo (Day 1: 8 trials, 1762 patients; relative risk [RR]=0.92; 95% confidence interval [CI], 0.78-1.1; Day 7: 5 trials, 1530 patients; RR=0.86; 95% CI, 0.70-1.1). Length of hospital stay didn’t differ between children treated with corticosteroids and children who received placebo (8 trials, 633 patients; mean difference= −0.18 days; 95% CI, −0.39 to 0.04).

Corticosteroid + epinephrine can lower hospital admissions

A 2009 multicenter, double-blind RCT with 800 patients (infants 6 weeks to 12 months of age with a first episode of bronchiolitis) that was included in the 2013 Cochrane review also compared the combination of epinephrine and corticosteroid with placebo and either agent alone.²

Infants were assigned to 4 groups: oral dexamethasone alone (1 mg/kg in the emergency room [ER] on Day 1, followed by 0.6 mg/kg daily for 5 days); nebulized epinephrine alone (2 treatments of 3 mL epinephrine 1:1000 solution); combined dexamethasone and epinephrine; and placebo. The primary outcome was hospital admission as long as 7 days after being seen in the ER.

Rates of admission were similar for the dexamethasone and placebo groups (25.6% vs 26.4%, respectively; RR=0.96; 95% CI, 0.69-1.3). The epinephrine group’s rate of admission was 23.7% (RR=0.88; CI, 0.63–1.23). Only the dexamethasone-epinephrine group had a lower rate of admission compared with placebo (17% vs 26%; RR=0.65; 95% CI, 0.45-0.95). The number needed to treat with dexamethasone-epinephrine to prevent one hospital admission was 11.

Review prompts revised recommendations

Based on the Cochrane review, the American Academy of Pediatrics (AAP) revised its evidence-based clinical practice guideline in 2014 to recommend that clinicians not administer systemic corticosteroids to infants with a diagnosis of bronchiolitis in any setting (evidence quality B, strong recommendation, based on results of multiple RCTs).³ The AAP advocates additional large trials to clarify whether combination therapy (corticosteroids plus agents with α or β agonist activity) is effective.

Evidence summary

A 2013 Cochrane review of 17 RCTs with 2596 patients compared corticosteroids with placebo for treating bronchiolitis in children younger than 2 years.¹ The studies used dexamethasone, prednisolone, prednisone, and budesonide delivered by oral, inhaled, intravenous (IV), or intramuscular (IM) routes, ranging between a one-day dose to a 5-day taper. Doses ranged from 0.5 to 2 mg/kg/d for oral and parenteral routes and 0.2 to 1 mg for inhalation. Outcomes were rate of admissions at Days 1 and 7 from outpatient trials and length of stay among inpatients.

Investigators found no significant difference in admission rates at Day 1 and Day 7 between children treated with corticosteroids compared with placebo (Day 1: 8 trials, 1762 patients; relative risk [RR]=0.92; 95% confidence interval [CI], 0.78-1.1; Day 7: 5 trials, 1530 patients; RR=0.86; 95% CI, 0.70-1.1). Length of hospital stay didn’t differ between children treated with corticosteroids and children who received placebo (8 trials, 633 patients; mean difference= −0.18 days; 95% CI, −0.39 to 0.04).

Corticosteroid + epinephrine can lower hospital admissions

A 2009 multicenter, double-blind RCT with 800 patients (infants 6 weeks to 12 months of age with a first episode of bronchiolitis) that was included in the 2013 Cochrane review also compared the combination of epinephrine and corticosteroid with placebo and either agent alone.²

Infants were assigned to 4 groups: oral dexamethasone alone (1 mg/kg in the emergency room [ER] on Day 1, followed by 0.6 mg/kg daily for 5 days); nebulized epinephrine alone (2 treatments of 3 mL epinephrine 1:1000 solution); combined dexamethasone and epinephrine; and placebo. The primary outcome was hospital admission as long as 7 days after being seen in the ER.

Rates of admission were similar for the dexamethasone and placebo groups (25.6% vs 26.4%, respectively; RR=0.96; 95% CI, 0.69-1.3). The epinephrine group’s rate of admission was 23.7% (RR=0.88; CI, 0.63–1.23). Only the dexamethasone-epinephrine group had a lower rate of admission compared with placebo (17% vs 26%; RR=0.65; 95% CI, 0.45-0.95). The number needed to treat with dexamethasone-epinephrine to prevent one hospital admission was 11.

Review prompts revised recommendations

Based on the Cochrane review, the American Academy of Pediatrics (AAP) revised its evidence-based clinical practice guideline in 2014 to recommend that clinicians not administer systemic corticosteroids to infants with a diagnosis of bronchiolitis in any setting (evidence quality B, strong recommendation, based on results of multiple RCTs).³ The AAP advocates additional large trials to clarify whether combination therapy (corticosteroids plus agents with α or β agonist activity) is effective.