What's Your Diagnosis?

A previously healthy 31-year-old female active-duty Navy sailor working as a calibration technician developed a painful, erythematous, pruritic, indurated plaque on her left breast. The sailor was not lactating and had no known family history of malignancy. Initially, she was treated by her primary care practitioner for presumed mastitis with oral cephalexin and then with oral clindamycin with no symptom improvement. About 2 weeks after the completion of both antibiotic courses, she developed angioedema and periorbital edema (Figure 1), requiring highdose corticosteroids and antihistamines with a corticosteroid course of prednisone 40 mg daily tapered to 10 mg daily over 12 days and diphenhydramine 25 mg to use up to 4 times daily. Workup for both was acquired and hereditary angioedema was unremarkable. Two months later, the patient developed patches of alopecia, oral ulcerations, and hypopigmented plaques with a peripheral hyperpigmented rim on the central face and bilateral conchal bowls (Figure 2). She also developed hypopigmented papules with peripheral hyperpigmentation on the bilateral dorsal hands overlying the metacarpal and proximal interphalangeal joints, which eventually ulcerated (Figure 3). Laboratory evaluation, including tests for creatine kinase, aldolase, transaminases, lactate dehydrogenase, and autoantibodies (antiJo-1, anti-Mi-2, anti-MDA-5, anti-TIF-1, anti-NXP-2, and anti-SAEP), were unremarkable. A punch biopsy from a papule on the right dorsal hand showed superficial perivascular lymphohistiocytic inflammation with a subtle focal increase in dermal mucin, highlighted by the colloidal iron stain. Further evaluation of the left breast plaque revealed ER/PR+ HER2- stage IIIB inflammatory breast cancer.

DISCUSSION

Based on the clinical presentation and diagnosis of inflammatory breast cancer, the patient was diagnosed with paraneoplastic clinically amyopathic dermatomyositis (CADM). She was treated for her breast cancer with an initial chemotherapy regimen consisting of dose-dense cyclophosphamide and doxorubicin followed by paclitaxel. The patient underwent a mastectomy, axillary lymph node dissection, and 25 sessions of radiation therapy, and is currently continuing therapy with anastrozole 1 mg daily and ovarian suppression with leuprorelin 11.25 mg every 3 months. For the severe angioedema and dermatomyositis-like cutaneous findings, the patient was continued on high-dose corticosteroids at prednisone 60 mg daily with a prolonged taper to prednisone 10 mg daily. After about 10 months, she transitioned from prednisone 10 mg daily to hydrocortisone 30 mg daily and is currently tapering her hydrocortisone dosing. She was additionally started on monthly intravenous immunoglobulin, hydroxychloroquine 300 mg daily, and amlodipine 5 mg daily. The ulcerated papules on her hands were treated with topical clobetasol 0.05% ointment applied daily, topical tacrolimus 0.1% ointment applied daily, and multiple intralesional triamcinolone 5 mg/mL injections. With this regimen, the patient experienced significant improvement in her cutaneous symptoms.

CADM is a rare autoimmune inflammatory disease featuring classic dermatomyositis-like cutaneous findings such as a heliotrope rash and Gottron papules. Ulcerative Gottron papules are less common than the typical erythematous papules and are associated more strongly with amyopathic disease.1 Paraneoplastic myositis poses a diagnostic challenge because it presents like an idiopathic dermatomyositis and often has a heterogeneous clinical presentation with additional manifestations, including periorbital edema, myalgias, dysphagia, and shortness of breath. If clinically suspected, laboratory tests (eg, creatine kinase, aldolase, transaminases, and lactate dehydrogenase) can assist in diagnosing paraneoplastic myositis. Additionally, serologic testing for autoantibodies such as anti-CADM-140, anti-Jo-1, anti-Mi-2, antiMDA-5, anti-TIF-1, anti-NXP-2, and antiSAE can assist the diagnosis and predict disease phenotype.^1,2

Malignancy can precede, occur during, or develop after the diagnosis of CADM.³ Malignancies most often associated with CADM include ovarian, breast, and lung cancers.⁴ Despite the strong correlation with malignancy, there are currently no screening guidelines for malignancy upon inflammatory myositis diagnosis. Therefore, it is important to consider the entirety of a patient’s clinical presentation in establishing further evaluation in the initial diagnostic workup.

There are numerous systemic complications associated with inflammatory myositis and imaging modalities can help to rule out some of these conditions. CADM is strongly associated with the development of interstitial lung disease, so chest radiography and pulmonary function testing are often checked.¹ Though cardiac and esophageal involvement are more commonly associated with classic dermatomyositis, it may be useful to obtain an electrocardiogram to rule out conduction abnormalities from myocardial involvement, along with esophageal manometry to evaluate for esophageal dysmotility.^1,5

In the management of paraneoplastic CADM, the underlying malignancy should be treated first.⁶ If symptoms persist after the cancer is in remission, then CADM is treated with immunosuppressive medications such as methotrexate, mycophenolate mofetil, or azathioprine. Physical therapy can also provide further symptom relief for those suffering from proximal weakness.

CONCLUSIONS

Presumed mastitis, angioedema, and eczematous lesions for this patient were dermatologic manifestations of an underlying inflammatory breast cancer. This case highlights the importance of early recognition, the diagnosis of CADM and awareness of its association with underlying malignancy, especially within the primary care setting where most skin concerns are addressed. Early clinical suspicion and a swift diagnostic workup can further optimize multidisciplinary management, which is often required to treat malignancies.

A previously healthy 31-year-old female active-duty Navy sailor working as a calibration technician developed a painful, erythematous, pruritic, indurated plaque on her left breast. The sailor was not lactating and had no known family history of malignancy. Initially, she was treated by her primary care practitioner for presumed mastitis with oral cephalexin and then with oral clindamycin with no symptom improvement. About 2 weeks after the completion of both antibiotic courses, she developed angioedema and periorbital edema (Figure 1), requiring highdose corticosteroids and antihistamines with a corticosteroid course of prednisone 40 mg daily tapered to 10 mg daily over 12 days and diphenhydramine 25 mg to use up to 4 times daily. Workup for both was acquired and hereditary angioedema was unremarkable. Two months later, the patient developed patches of alopecia, oral ulcerations, and hypopigmented plaques with a peripheral hyperpigmented rim on the central face and bilateral conchal bowls (Figure 2). She also developed hypopigmented papules with peripheral hyperpigmentation on the bilateral dorsal hands overlying the metacarpal and proximal interphalangeal joints, which eventually ulcerated (Figure 3). Laboratory evaluation, including tests for creatine kinase, aldolase, transaminases, lactate dehydrogenase, and autoantibodies (antiJo-1, anti-Mi-2, anti-MDA-5, anti-TIF-1, anti-NXP-2, and anti-SAEP), were unremarkable. A punch biopsy from a papule on the right dorsal hand showed superficial perivascular lymphohistiocytic inflammation with a subtle focal increase in dermal mucin, highlighted by the colloidal iron stain. Further evaluation of the left breast plaque revealed ER/PR+ HER2- stage IIIB inflammatory breast cancer.

DISCUSSION

Based on the clinical presentation and diagnosis of inflammatory breast cancer, the patient was diagnosed with paraneoplastic clinically amyopathic dermatomyositis (CADM). She was treated for her breast cancer with an initial chemotherapy regimen consisting of dose-dense cyclophosphamide and doxorubicin followed by paclitaxel. The patient underwent a mastectomy, axillary lymph node dissection, and 25 sessions of radiation therapy, and is currently continuing therapy with anastrozole 1 mg daily and ovarian suppression with leuprorelin 11.25 mg every 3 months. For the severe angioedema and dermatomyositis-like cutaneous findings, the patient was continued on high-dose corticosteroids at prednisone 60 mg daily with a prolonged taper to prednisone 10 mg daily. After about 10 months, she transitioned from prednisone 10 mg daily to hydrocortisone 30 mg daily and is currently tapering her hydrocortisone dosing. She was additionally started on monthly intravenous immunoglobulin, hydroxychloroquine 300 mg daily, and amlodipine 5 mg daily. The ulcerated papules on her hands were treated with topical clobetasol 0.05% ointment applied daily, topical tacrolimus 0.1% ointment applied daily, and multiple intralesional triamcinolone 5 mg/mL injections. With this regimen, the patient experienced significant improvement in her cutaneous symptoms.

CADM is a rare autoimmune inflammatory disease featuring classic dermatomyositis-like cutaneous findings such as a heliotrope rash and Gottron papules. Ulcerative Gottron papules are less common than the typical erythematous papules and are associated more strongly with amyopathic disease.1 Paraneoplastic myositis poses a diagnostic challenge because it presents like an idiopathic dermatomyositis and often has a heterogeneous clinical presentation with additional manifestations, including periorbital edema, myalgias, dysphagia, and shortness of breath. If clinically suspected, laboratory tests (eg, creatine kinase, aldolase, transaminases, and lactate dehydrogenase) can assist in diagnosing paraneoplastic myositis. Additionally, serologic testing for autoantibodies such as anti-CADM-140, anti-Jo-1, anti-Mi-2, antiMDA-5, anti-TIF-1, anti-NXP-2, and antiSAE can assist the diagnosis and predict disease phenotype.^1,2

Malignancy can precede, occur during, or develop after the diagnosis of CADM.³ Malignancies most often associated with CADM include ovarian, breast, and lung cancers.⁴ Despite the strong correlation with malignancy, there are currently no screening guidelines for malignancy upon inflammatory myositis diagnosis. Therefore, it is important to consider the entirety of a patient’s clinical presentation in establishing further evaluation in the initial diagnostic workup.

There are numerous systemic complications associated with inflammatory myositis and imaging modalities can help to rule out some of these conditions. CADM is strongly associated with the development of interstitial lung disease, so chest radiography and pulmonary function testing are often checked.¹ Though cardiac and esophageal involvement are more commonly associated with classic dermatomyositis, it may be useful to obtain an electrocardiogram to rule out conduction abnormalities from myocardial involvement, along with esophageal manometry to evaluate for esophageal dysmotility.^1,5

In the management of paraneoplastic CADM, the underlying malignancy should be treated first.⁶ If symptoms persist after the cancer is in remission, then CADM is treated with immunosuppressive medications such as methotrexate, mycophenolate mofetil, or azathioprine. Physical therapy can also provide further symptom relief for those suffering from proximal weakness.

CONCLUSIONS

Presumed mastitis, angioedema, and eczematous lesions for this patient were dermatologic manifestations of an underlying inflammatory breast cancer. This case highlights the importance of early recognition, the diagnosis of CADM and awareness of its association with underlying malignancy, especially within the primary care setting where most skin concerns are addressed. Early clinical suspicion and a swift diagnostic workup can further optimize multidisciplinary management, which is often required to treat malignancies.

A previously healthy 31-year-old female active-duty Navy sailor working as a calibration technician developed a painful, erythematous, pruritic, indurated plaque on her left breast. The sailor was not lactating and had no known family history of malignancy. Initially, she was treated by her primary care practitioner for presumed mastitis with oral cephalexin and then with oral clindamycin with no symptom improvement. About 2 weeks after the completion of both antibiotic courses, she developed angioedema and periorbital edema (Figure 1), requiring highdose corticosteroids and antihistamines with a corticosteroid course of prednisone 40 mg daily tapered to 10 mg daily over 12 days and diphenhydramine 25 mg to use up to 4 times daily. Workup for both was acquired and hereditary angioedema was unremarkable. Two months later, the patient developed patches of alopecia, oral ulcerations, and hypopigmented plaques with a peripheral hyperpigmented rim on the central face and bilateral conchal bowls (Figure 2). She also developed hypopigmented papules with peripheral hyperpigmentation on the bilateral dorsal hands overlying the metacarpal and proximal interphalangeal joints, which eventually ulcerated (Figure 3). Laboratory evaluation, including tests for creatine kinase, aldolase, transaminases, lactate dehydrogenase, and autoantibodies (antiJo-1, anti-Mi-2, anti-MDA-5, anti-TIF-1, anti-NXP-2, and anti-SAEP), were unremarkable. A punch biopsy from a papule on the right dorsal hand showed superficial perivascular lymphohistiocytic inflammation with a subtle focal increase in dermal mucin, highlighted by the colloidal iron stain. Further evaluation of the left breast plaque revealed ER/PR+ HER2- stage IIIB inflammatory breast cancer.

DISCUSSION

Based on the clinical presentation and diagnosis of inflammatory breast cancer, the patient was diagnosed with paraneoplastic clinically amyopathic dermatomyositis (CADM). She was treated for her breast cancer with an initial chemotherapy regimen consisting of dose-dense cyclophosphamide and doxorubicin followed by paclitaxel. The patient underwent a mastectomy, axillary lymph node dissection, and 25 sessions of radiation therapy, and is currently continuing therapy with anastrozole 1 mg daily and ovarian suppression with leuprorelin 11.25 mg every 3 months. For the severe angioedema and dermatomyositis-like cutaneous findings, the patient was continued on high-dose corticosteroids at prednisone 60 mg daily with a prolonged taper to prednisone 10 mg daily. After about 10 months, she transitioned from prednisone 10 mg daily to hydrocortisone 30 mg daily and is currently tapering her hydrocortisone dosing. She was additionally started on monthly intravenous immunoglobulin, hydroxychloroquine 300 mg daily, and amlodipine 5 mg daily. The ulcerated papules on her hands were treated with topical clobetasol 0.05% ointment applied daily, topical tacrolimus 0.1% ointment applied daily, and multiple intralesional triamcinolone 5 mg/mL injections. With this regimen, the patient experienced significant improvement in her cutaneous symptoms.

CADM is a rare autoimmune inflammatory disease featuring classic dermatomyositis-like cutaneous findings such as a heliotrope rash and Gottron papules. Ulcerative Gottron papules are less common than the typical erythematous papules and are associated more strongly with amyopathic disease.1 Paraneoplastic myositis poses a diagnostic challenge because it presents like an idiopathic dermatomyositis and often has a heterogeneous clinical presentation with additional manifestations, including periorbital edema, myalgias, dysphagia, and shortness of breath. If clinically suspected, laboratory tests (eg, creatine kinase, aldolase, transaminases, and lactate dehydrogenase) can assist in diagnosing paraneoplastic myositis. Additionally, serologic testing for autoantibodies such as anti-CADM-140, anti-Jo-1, anti-Mi-2, antiMDA-5, anti-TIF-1, anti-NXP-2, and antiSAE can assist the diagnosis and predict disease phenotype.^1,2

Malignancy can precede, occur during, or develop after the diagnosis of CADM.³ Malignancies most often associated with CADM include ovarian, breast, and lung cancers.⁴ Despite the strong correlation with malignancy, there are currently no screening guidelines for malignancy upon inflammatory myositis diagnosis. Therefore, it is important to consider the entirety of a patient’s clinical presentation in establishing further evaluation in the initial diagnostic workup.

There are numerous systemic complications associated with inflammatory myositis and imaging modalities can help to rule out some of these conditions. CADM is strongly associated with the development of interstitial lung disease, so chest radiography and pulmonary function testing are often checked.¹ Though cardiac and esophageal involvement are more commonly associated with classic dermatomyositis, it may be useful to obtain an electrocardiogram to rule out conduction abnormalities from myocardial involvement, along with esophageal manometry to evaluate for esophageal dysmotility.^1,5

In the management of paraneoplastic CADM, the underlying malignancy should be treated first.⁶ If symptoms persist after the cancer is in remission, then CADM is treated with immunosuppressive medications such as methotrexate, mycophenolate mofetil, or azathioprine. Physical therapy can also provide further symptom relief for those suffering from proximal weakness.

CONCLUSIONS

Presumed mastitis, angioedema, and eczematous lesions for this patient were dermatologic manifestations of an underlying inflammatory breast cancer. This case highlights the importance of early recognition, the diagnosis of CADM and awareness of its association with underlying malignancy, especially within the primary care setting where most skin concerns are addressed. Early clinical suspicion and a swift diagnostic workup can further optimize multidisciplinary management, which is often required to treat malignancies.

A 35-year-old woman with a history of hypothyroidism and idiopathic small fiber autonomic and sensory neuropathy presented to the emergency department (ED) 48 hours after IV immunoglobulin (IG) infusion with a severe headache, nausea, neck stiffness, photophobia, and episodes of intense positional eye pressure. The patient reported previous episodes of headaches post-IVIG infusion but not nearly as severe. On ED arrival, the patient was afebrile with vital signs within normal limits. Initial laboratory results were notable for levels within reference range parameters: 5.9 × 10⁹/L white blood cell (WBC) count, 13.3 g/dL hemoglobin, 38.7% hematocrit, and 279 × 10⁹/L platelet count; there were no abnormal urinalysis findings, and she was negative for human chorionic gonadotropin.

Due to the patient’s symptoms concerning for an acute intracranial process, a brain computed tomography (CT) without contrast was ordered. The CT demonstrated no intracranial abnormalities, but the patient’s symptoms continued to worsen. The patient was started on IV fluids and 1 g IV acetaminophen and underwent a lumbar puncture (LP). Her opening pressure was elevated at 29 cm H₂O (reference range, 6-20 cm), and the fluid was notably clear. During the LP, 25 mL of cerebrospinal fluid (CSF) was collected for laboratory analysis to include a polymerase chain reaction (PCR) panel and cultures, and a closing pressure of 12 cm H₂O was recorded at the end of the procedure with the patient reporting some relief of pressure. The patient was admitted to the medicine ward for further workup and observations.The patient’s meningitis/encephalitis PCR panel detected no pathogens in the CSF, but her WBC count was 84 × 10⁹/L (reference range, 4-11) with 30 segmented neutrophils (reference range, 0-6) and red blood cell count of 24 (reference range, 0-1); her normal glucose at 60 mg/dL (reference range, 40-70) and protein of 33 mg/dL (reference range, 15-45) were within normal parameters. Brain magnetic resonance images with and without contrast was inconsistent with any acute intracranial pathology to include subarachnoid hemorrhage or central nervous system neoplasm (Figure 1). Bacterial and fungal cultures were negative.

• What is your diagnosis?
• How would you treat this patient?

Discussion

Aseptic meningitis presents with a typical clinical picture of meningitis to include headache, stiffened neck, and photophobia. In the event of negative CSF bacterial and fungal cultures and negative viral PCR, a diagnosis of aseptic meningitis is considered.¹ Though the differential for aseptic meningitis is broad, in the immunocompetent patient, the most common etiology of aseptic meningitis in the United States is by far viral, and specifically, enterovirus (50.9%). It is less commonly caused by herpes simplex virus (8.3%), varicella zoster virus, and finally, the mosquito-borne St. Louis encephalitis and West Nile viruses typically acquired in the summer or early fall months. Other infectious agents that can present with aseptic meningitis are spirochetes (Lyme disease and syphilis), tuberculous meningitis, fungal infections (cryptococcal meningitis), and other bacterial infections that have a negative culture. Once an infectious cause becomes low on the differential, the remaining 3.5% of cases can be attributed to a noninfectious aseptic etiology.² This includes neoplasia, autoimmune, auto-inflammatory, iatrogenic, and drug induced (the most common subtype of this category) as possible causes.

The patient’s history, physical examination, vital signs, imaging, and lumbar puncture findings were most concerning for drug-induced aseptic meningitis (DIAM) secondary to her recent IVIG infusion. An algorithm can be used to work through the diagnostic approach (Figure 2).^3,4

Conclusions

We encourage heightened clinical suspicion of DIAM in patients who have recently undergone IVIG infusion and present with meningeal signs (stiff neck, headache, photophobia, and ear/eye pressure) without any evidence of infection on physical examination or laboratory results. With such, we hope to improve clinician suspicion, detection, as well as patient education and outcomes in cases of DIAM.

A 35-year-old woman with a history of hypothyroidism and idiopathic small fiber autonomic and sensory neuropathy presented to the emergency department (ED) 48 hours after IV immunoglobulin (IG) infusion with a severe headache, nausea, neck stiffness, photophobia, and episodes of intense positional eye pressure. The patient reported previous episodes of headaches post-IVIG infusion but not nearly as severe. On ED arrival, the patient was afebrile with vital signs within normal limits. Initial laboratory results were notable for levels within reference range parameters: 5.9 × 10⁹/L white blood cell (WBC) count, 13.3 g/dL hemoglobin, 38.7% hematocrit, and 279 × 10⁹/L platelet count; there were no abnormal urinalysis findings, and she was negative for human chorionic gonadotropin.

Due to the patient’s symptoms concerning for an acute intracranial process, a brain computed tomography (CT) without contrast was ordered. The CT demonstrated no intracranial abnormalities, but the patient’s symptoms continued to worsen. The patient was started on IV fluids and 1 g IV acetaminophen and underwent a lumbar puncture (LP). Her opening pressure was elevated at 29 cm H₂O (reference range, 6-20 cm), and the fluid was notably clear. During the LP, 25 mL of cerebrospinal fluid (CSF) was collected for laboratory analysis to include a polymerase chain reaction (PCR) panel and cultures, and a closing pressure of 12 cm H₂O was recorded at the end of the procedure with the patient reporting some relief of pressure. The patient was admitted to the medicine ward for further workup and observations.The patient’s meningitis/encephalitis PCR panel detected no pathogens in the CSF, but her WBC count was 84 × 10⁹/L (reference range, 4-11) with 30 segmented neutrophils (reference range, 0-6) and red blood cell count of 24 (reference range, 0-1); her normal glucose at 60 mg/dL (reference range, 40-70) and protein of 33 mg/dL (reference range, 15-45) were within normal parameters. Brain magnetic resonance images with and without contrast was inconsistent with any acute intracranial pathology to include subarachnoid hemorrhage or central nervous system neoplasm (Figure 1). Bacterial and fungal cultures were negative.

• What is your diagnosis?
• How would you treat this patient?

Discussion

Aseptic meningitis presents with a typical clinical picture of meningitis to include headache, stiffened neck, and photophobia. In the event of negative CSF bacterial and fungal cultures and negative viral PCR, a diagnosis of aseptic meningitis is considered.¹ Though the differential for aseptic meningitis is broad, in the immunocompetent patient, the most common etiology of aseptic meningitis in the United States is by far viral, and specifically, enterovirus (50.9%). It is less commonly caused by herpes simplex virus (8.3%), varicella zoster virus, and finally, the mosquito-borne St. Louis encephalitis and West Nile viruses typically acquired in the summer or early fall months. Other infectious agents that can present with aseptic meningitis are spirochetes (Lyme disease and syphilis), tuberculous meningitis, fungal infections (cryptococcal meningitis), and other bacterial infections that have a negative culture. Once an infectious cause becomes low on the differential, the remaining 3.5% of cases can be attributed to a noninfectious aseptic etiology.² This includes neoplasia, autoimmune, auto-inflammatory, iatrogenic, and drug induced (the most common subtype of this category) as possible causes.

The patient’s history, physical examination, vital signs, imaging, and lumbar puncture findings were most concerning for drug-induced aseptic meningitis (DIAM) secondary to her recent IVIG infusion. An algorithm can be used to work through the diagnostic approach (Figure 2).^3,4

Conclusions

We encourage heightened clinical suspicion of DIAM in patients who have recently undergone IVIG infusion and present with meningeal signs (stiff neck, headache, photophobia, and ear/eye pressure) without any evidence of infection on physical examination or laboratory results. With such, we hope to improve clinician suspicion, detection, as well as patient education and outcomes in cases of DIAM.

A 35-year-old woman with a history of hypothyroidism and idiopathic small fiber autonomic and sensory neuropathy presented to the emergency department (ED) 48 hours after IV immunoglobulin (IG) infusion with a severe headache, nausea, neck stiffness, photophobia, and episodes of intense positional eye pressure. The patient reported previous episodes of headaches post-IVIG infusion but not nearly as severe. On ED arrival, the patient was afebrile with vital signs within normal limits. Initial laboratory results were notable for levels within reference range parameters: 5.9 × 10⁹/L white blood cell (WBC) count, 13.3 g/dL hemoglobin, 38.7% hematocrit, and 279 × 10⁹/L platelet count; there were no abnormal urinalysis findings, and she was negative for human chorionic gonadotropin.

Due to the patient’s symptoms concerning for an acute intracranial process, a brain computed tomography (CT) without contrast was ordered. The CT demonstrated no intracranial abnormalities, but the patient’s symptoms continued to worsen. The patient was started on IV fluids and 1 g IV acetaminophen and underwent a lumbar puncture (LP). Her opening pressure was elevated at 29 cm H₂O (reference range, 6-20 cm), and the fluid was notably clear. During the LP, 25 mL of cerebrospinal fluid (CSF) was collected for laboratory analysis to include a polymerase chain reaction (PCR) panel and cultures, and a closing pressure of 12 cm H₂O was recorded at the end of the procedure with the patient reporting some relief of pressure. The patient was admitted to the medicine ward for further workup and observations.The patient’s meningitis/encephalitis PCR panel detected no pathogens in the CSF, but her WBC count was 84 × 10⁹/L (reference range, 4-11) with 30 segmented neutrophils (reference range, 0-6) and red blood cell count of 24 (reference range, 0-1); her normal glucose at 60 mg/dL (reference range, 40-70) and protein of 33 mg/dL (reference range, 15-45) were within normal parameters. Brain magnetic resonance images with and without contrast was inconsistent with any acute intracranial pathology to include subarachnoid hemorrhage or central nervous system neoplasm (Figure 1). Bacterial and fungal cultures were negative.

• What is your diagnosis?
• How would you treat this patient?

Discussion

Aseptic meningitis presents with a typical clinical picture of meningitis to include headache, stiffened neck, and photophobia. In the event of negative CSF bacterial and fungal cultures and negative viral PCR, a diagnosis of aseptic meningitis is considered.¹ Though the differential for aseptic meningitis is broad, in the immunocompetent patient, the most common etiology of aseptic meningitis in the United States is by far viral, and specifically, enterovirus (50.9%). It is less commonly caused by herpes simplex virus (8.3%), varicella zoster virus, and finally, the mosquito-borne St. Louis encephalitis and West Nile viruses typically acquired in the summer or early fall months. Other infectious agents that can present with aseptic meningitis are spirochetes (Lyme disease and syphilis), tuberculous meningitis, fungal infections (cryptococcal meningitis), and other bacterial infections that have a negative culture. Once an infectious cause becomes low on the differential, the remaining 3.5% of cases can be attributed to a noninfectious aseptic etiology.² This includes neoplasia, autoimmune, auto-inflammatory, iatrogenic, and drug induced (the most common subtype of this category) as possible causes.

The patient’s history, physical examination, vital signs, imaging, and lumbar puncture findings were most concerning for drug-induced aseptic meningitis (DIAM) secondary to her recent IVIG infusion. An algorithm can be used to work through the diagnostic approach (Figure 2).^3,4

Conclusions

We encourage heightened clinical suspicion of DIAM in patients who have recently undergone IVIG infusion and present with meningeal signs (stiff neck, headache, photophobia, and ear/eye pressure) without any evidence of infection on physical examination or laboratory results. With such, we hope to improve clinician suspicion, detection, as well as patient education and outcomes in cases of DIAM.

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

A 53-year-old male patient presented to the emergency department following a primary care office visit with sudden onset right upper quadrant abdominal pain that persisted for 3 weeks, worsening over the last 2 days. The abdominal pain worsened after eating or drinking and mildly improved with omeprazole. Associated symptoms included intermittent fever, night sweats, fatigue, and bloating since onset without vomiting or diarrhea. He reported a “complicated” cholecystectomy at an outside facility 6 months prior and that his “gallbladder was adhered to his duodenum,” though outside records were not available. Additional medical history included diverticulosis with prior flares of diverticulitis but no recent flares or treatments. His home medications included acetaminophen, naproxen, intranasal fluticasone, omeprazole, gabapentin, baclofen, trazodone, and antihistamines. He reported no tobacco or illicit drug use and stated he consumed a 6 pack of beer every 6 weeks.

Initial vital signs in the emergency department demonstrated an afebrile oral temperature with unremarkable blood pressure and pulse. He was alert and oriented and did not appear in significant acute distress. Physical examination of the abdomen demonstrated a nondistended abdomen, normal active bowel sounds in all 4 quadrants, and mild right upper and lower quadrant tenderness to soft and deep palpation with release.

Significant laboratory values included elevated C-reactive protein of 44.1 mg/L and mild leukocytosis of 11.1 K/µL (reference range, 4.00-10.60 K/µL). The basic metabolic panel, liver-associated enzymes, and lipase levels were within normal limits.

• What is your diagnosis?
• How would you treat this patient?
   

   

Our Diagnosis

Based on the clinical history of postprandial abdominal pain with prior cholecystectomy and leukocytosis, the initial differential diagnosis included peptic ulcer disease, gastroesophageal reflux, or delayed sequela of the cholecystectomy 6 months prior. Although suspicion remained for possible delayed postoperative complications from the cholecystectomy, ultrasound and hepatobiliary iminodiacetic acid (HIDA) scan were not pursued based on CT imaging findings. The needle-like hypodensity in the duodenum with surrounding inflammation visualized on CT was concerning for an unidentified penetrating foreign body with a possible retroperitoneal microperforation.

After these imaging findings were relayed from Radiology to the Gastroenterology Service, the patient underwent an upper gastrointestinal (GI) endoscopy to further evaluate the duodenum. Inspection revealed mild gastritis and a linear, clear piece of plastic with both ends firmly lodged within the mucosa from the distal duodenal bulb to the second portion of the duodenum; a significant mucosal defect of the bowel wall was visualized after careful extraction of the foreign body (Figure 2). The patient was diagnosed with a small duodenal perforation, which was sealed endoscopically with 2 endoclips. The extracted piece of plastic was examined and determined to be a broken cocktail pick (Figure 3). During discussion with the patient postprocedure, he stated that he ingested several olive martinis (which were served with cocktail picks) approximately 3 weeks prior to presentation and did not recall ingesting the cocktail pick. A repeat abdominal CT following the endoscopy demonstrated no leak or free air from the site of the repaired duodenal perforation (Figure 4). The patient avoided surgery and was permitted to resume a liquid diet prior to discharge.

Discussion

Foreign body ingestion in adults is most commonly unintentional with fish bones being the most common culprit.¹ In unintentional instances of foreign body ingestion, many patients are not aware of the event, with dentures posing a significant well-known risk factor due to lack of palatal sensory feedback.² Most ingested foreign bodies pass uninhibited through the GI tract without complications. However, less than 1% of ingested foreign bodies cause potentially life-threatening GI perforations.³

The risk of GI perforation due to foreign body ingestion is greatest with elongated, sharp objects, such as needles, bones, toothpicks, and cocktail picks. These objects tend to lodge at areas of narrowing or angulation, such as the appendix, ileocecal region, or as in this case, the duodenum.³ Passage of a foreign body through the duodenum is more likely to be inhibited if the object is longer than 6 cm and with a diameter > 2.5 cm.⁴ Signs of duodenal perforation are often subtle compared with jejunal or ileal perforations. Patients are commonly afebrile with normal white blood cell counts and are more likely to have chronic symptoms for > 3 days before the appropriate diagnosis of foreign body ingestion is made.¹ Duodenal perforations may be more stable clinically compared with distal GI perforations in part due to the retroperitoneal location with relatively fewer bacteria present intraluminally. GI perforations may not occur acutely during passage of the foreign body but can present weeks, months, or even years later.⁵ Delayed onset of symptoms may happen when the foreign body becomes lodged and only partially perforates the bowel wall, resulting in a chronic inflammatory process. Other possible complications include fistulization and abscess formation from migrating linear sharp objects through the bowel wall, which is most observed with toothpicks and cocktail picks, specifically.⁵

Foreign bodies identified on plain radiographs commonly include radiopaque objects, such as glass, metallic objects, most animal bones and some fish bones, and some medications. However, radiolucent objects, such as toothpicks and cocktail picks, wood, plastic, most fish bones, and most medicines, often will not appear on radiographs. The diagnosis of ingested foreign body can therefore easily be delayed or overlooked on plain radiographs due to ingestion of radiolucent objects or lack of adequate patient history. A high index of suspicion is needed in such instances. The modality of choice for identifying GI perforation due to ingested foreign objects is CT.⁵ All of these commonly missed materials on radiographs will be visible on CT with variable densities. As an added benefit, CT also may reveal ingested objects not visualized on radiographs and show ancillary signs of perforation, such as extraluminal free air, localized inflammation, and fluid collections or abscess surrounding a segment of thickened bowel.⁵

Most ingested foreign bodies will pass through the GI system and can be managed with careful observation alone. However, upper endoscopy is emergently indicated in 3 scenarios of foreign body ingestion: (1) complete occlusion of the esophagus with salivary pooling due to risk of aspiration; (2) ingestion of batteries due to toxic substances; and (3) ingestion of sharp or pointed foreign bodies due to risk of perforation.⁴ Overall, endoscopic intervention is required in 20% of cases and surgical intervention remains rare at 1%.⁴ In the case of this patient, an emergent upper endoscopy was needed due to suspected duodenal perforation.

Treatment of duodenal perforations due to foreign bodies may involve conservative, surgical, or endoscopic management. Contained, small perforations in a stable patient may be treated conservatively with IV fluids, antibiotics, and proton pump inhibitors as they self-seal with omentum if the foreign body has passed.⁶ Retained duodenal foreign bodies pose a risk of persistent perforation or fistulization and must be removed. Anterior duodenal perforations pose a risk of peritonitis, whereas posterior duodenal perforations, although retroperitoneal and sparing the peritoneal cavity, may result in localized abscess formation necessitating foreign body removal. Endoscopic clipping is a modernized, less invasive way to close GI perforations. Through-the-scope clips (TTSCs) can close luminal defects < 2 cm in size.⁷ Defects > 1 cm may be repaired with combined TTSCs and endoloop or omental patching. Over-the-scope clips can close full thickness defects up to 2 to 3 cm with the advantage of being able to close leaks and fistulas involving inflamed or indurated tissue.⁷

Conclusions

Intestinal perforations related to foreign body ingestion are a rare complication occurring in < 1% of patients. Although most ingested foreign objects will pass through the GI tract, elongated or sharp objects pose a risk for perforation. In many cases, a history of foreign body ingestion is not obtained, and a high index of suspicion is required. Duodenal perforations due to foreign body ingestion should be included in the differential among the more common diagnoses of peptic ulcers, pancreatitis, and gallbladder disease in the setting of postprandial right upper quadrant abdominal pain. CT is the best modality for identifying foreign bodies, including objects that may be missed on plain radiographs.

A 53-year-old male patient presented to the emergency department following a primary care office visit with sudden onset right upper quadrant abdominal pain that persisted for 3 weeks, worsening over the last 2 days. The abdominal pain worsened after eating or drinking and mildly improved with omeprazole. Associated symptoms included intermittent fever, night sweats, fatigue, and bloating since onset without vomiting or diarrhea. He reported a “complicated” cholecystectomy at an outside facility 6 months prior and that his “gallbladder was adhered to his duodenum,” though outside records were not available. Additional medical history included diverticulosis with prior flares of diverticulitis but no recent flares or treatments. His home medications included acetaminophen, naproxen, intranasal fluticasone, omeprazole, gabapentin, baclofen, trazodone, and antihistamines. He reported no tobacco or illicit drug use and stated he consumed a 6 pack of beer every 6 weeks.

Initial vital signs in the emergency department demonstrated an afebrile oral temperature with unremarkable blood pressure and pulse. He was alert and oriented and did not appear in significant acute distress. Physical examination of the abdomen demonstrated a nondistended abdomen, normal active bowel sounds in all 4 quadrants, and mild right upper and lower quadrant tenderness to soft and deep palpation with release.

Significant laboratory values included elevated C-reactive protein of 44.1 mg/L and mild leukocytosis of 11.1 K/µL (reference range, 4.00-10.60 K/µL). The basic metabolic panel, liver-associated enzymes, and lipase levels were within normal limits.

• What is your diagnosis?
• How would you treat this patient?
   

   

Our Diagnosis

Based on the clinical history of postprandial abdominal pain with prior cholecystectomy and leukocytosis, the initial differential diagnosis included peptic ulcer disease, gastroesophageal reflux, or delayed sequela of the cholecystectomy 6 months prior. Although suspicion remained for possible delayed postoperative complications from the cholecystectomy, ultrasound and hepatobiliary iminodiacetic acid (HIDA) scan were not pursued based on CT imaging findings. The needle-like hypodensity in the duodenum with surrounding inflammation visualized on CT was concerning for an unidentified penetrating foreign body with a possible retroperitoneal microperforation.

After these imaging findings were relayed from Radiology to the Gastroenterology Service, the patient underwent an upper gastrointestinal (GI) endoscopy to further evaluate the duodenum. Inspection revealed mild gastritis and a linear, clear piece of plastic with both ends firmly lodged within the mucosa from the distal duodenal bulb to the second portion of the duodenum; a significant mucosal defect of the bowel wall was visualized after careful extraction of the foreign body (Figure 2). The patient was diagnosed with a small duodenal perforation, which was sealed endoscopically with 2 endoclips. The extracted piece of plastic was examined and determined to be a broken cocktail pick (Figure 3). During discussion with the patient postprocedure, he stated that he ingested several olive martinis (which were served with cocktail picks) approximately 3 weeks prior to presentation and did not recall ingesting the cocktail pick. A repeat abdominal CT following the endoscopy demonstrated no leak or free air from the site of the repaired duodenal perforation (Figure 4). The patient avoided surgery and was permitted to resume a liquid diet prior to discharge.

Discussion

Foreign body ingestion in adults is most commonly unintentional with fish bones being the most common culprit.¹ In unintentional instances of foreign body ingestion, many patients are not aware of the event, with dentures posing a significant well-known risk factor due to lack of palatal sensory feedback.² Most ingested foreign bodies pass uninhibited through the GI tract without complications. However, less than 1% of ingested foreign bodies cause potentially life-threatening GI perforations.³

The risk of GI perforation due to foreign body ingestion is greatest with elongated, sharp objects, such as needles, bones, toothpicks, and cocktail picks. These objects tend to lodge at areas of narrowing or angulation, such as the appendix, ileocecal region, or as in this case, the duodenum.³ Passage of a foreign body through the duodenum is more likely to be inhibited if the object is longer than 6 cm and with a diameter > 2.5 cm.⁴ Signs of duodenal perforation are often subtle compared with jejunal or ileal perforations. Patients are commonly afebrile with normal white blood cell counts and are more likely to have chronic symptoms for > 3 days before the appropriate diagnosis of foreign body ingestion is made.¹ Duodenal perforations may be more stable clinically compared with distal GI perforations in part due to the retroperitoneal location with relatively fewer bacteria present intraluminally. GI perforations may not occur acutely during passage of the foreign body but can present weeks, months, or even years later.⁵ Delayed onset of symptoms may happen when the foreign body becomes lodged and only partially perforates the bowel wall, resulting in a chronic inflammatory process. Other possible complications include fistulization and abscess formation from migrating linear sharp objects through the bowel wall, which is most observed with toothpicks and cocktail picks, specifically.⁵

Foreign bodies identified on plain radiographs commonly include radiopaque objects, such as glass, metallic objects, most animal bones and some fish bones, and some medications. However, radiolucent objects, such as toothpicks and cocktail picks, wood, plastic, most fish bones, and most medicines, often will not appear on radiographs. The diagnosis of ingested foreign body can therefore easily be delayed or overlooked on plain radiographs due to ingestion of radiolucent objects or lack of adequate patient history. A high index of suspicion is needed in such instances. The modality of choice for identifying GI perforation due to ingested foreign objects is CT.⁵ All of these commonly missed materials on radiographs will be visible on CT with variable densities. As an added benefit, CT also may reveal ingested objects not visualized on radiographs and show ancillary signs of perforation, such as extraluminal free air, localized inflammation, and fluid collections or abscess surrounding a segment of thickened bowel.⁵

Most ingested foreign bodies will pass through the GI system and can be managed with careful observation alone. However, upper endoscopy is emergently indicated in 3 scenarios of foreign body ingestion: (1) complete occlusion of the esophagus with salivary pooling due to risk of aspiration; (2) ingestion of batteries due to toxic substances; and (3) ingestion of sharp or pointed foreign bodies due to risk of perforation.⁴ Overall, endoscopic intervention is required in 20% of cases and surgical intervention remains rare at 1%.⁴ In the case of this patient, an emergent upper endoscopy was needed due to suspected duodenal perforation.

Treatment of duodenal perforations due to foreign bodies may involve conservative, surgical, or endoscopic management. Contained, small perforations in a stable patient may be treated conservatively with IV fluids, antibiotics, and proton pump inhibitors as they self-seal with omentum if the foreign body has passed.⁶ Retained duodenal foreign bodies pose a risk of persistent perforation or fistulization and must be removed. Anterior duodenal perforations pose a risk of peritonitis, whereas posterior duodenal perforations, although retroperitoneal and sparing the peritoneal cavity, may result in localized abscess formation necessitating foreign body removal. Endoscopic clipping is a modernized, less invasive way to close GI perforations. Through-the-scope clips (TTSCs) can close luminal defects < 2 cm in size.⁷ Defects > 1 cm may be repaired with combined TTSCs and endoloop or omental patching. Over-the-scope clips can close full thickness defects up to 2 to 3 cm with the advantage of being able to close leaks and fistulas involving inflamed or indurated tissue.⁷

Conclusions

Intestinal perforations related to foreign body ingestion are a rare complication occurring in < 1% of patients. Although most ingested foreign objects will pass through the GI tract, elongated or sharp objects pose a risk for perforation. In many cases, a history of foreign body ingestion is not obtained, and a high index of suspicion is required. Duodenal perforations due to foreign body ingestion should be included in the differential among the more common diagnoses of peptic ulcers, pancreatitis, and gallbladder disease in the setting of postprandial right upper quadrant abdominal pain. CT is the best modality for identifying foreign bodies, including objects that may be missed on plain radiographs.

A 53-year-old male patient presented to the emergency department following a primary care office visit with sudden onset right upper quadrant abdominal pain that persisted for 3 weeks, worsening over the last 2 days. The abdominal pain worsened after eating or drinking and mildly improved with omeprazole. Associated symptoms included intermittent fever, night sweats, fatigue, and bloating since onset without vomiting or diarrhea. He reported a “complicated” cholecystectomy at an outside facility 6 months prior and that his “gallbladder was adhered to his duodenum,” though outside records were not available. Additional medical history included diverticulosis with prior flares of diverticulitis but no recent flares or treatments. His home medications included acetaminophen, naproxen, intranasal fluticasone, omeprazole, gabapentin, baclofen, trazodone, and antihistamines. He reported no tobacco or illicit drug use and stated he consumed a 6 pack of beer every 6 weeks.

Initial vital signs in the emergency department demonstrated an afebrile oral temperature with unremarkable blood pressure and pulse. He was alert and oriented and did not appear in significant acute distress. Physical examination of the abdomen demonstrated a nondistended abdomen, normal active bowel sounds in all 4 quadrants, and mild right upper and lower quadrant tenderness to soft and deep palpation with release.

Significant laboratory values included elevated C-reactive protein of 44.1 mg/L and mild leukocytosis of 11.1 K/µL (reference range, 4.00-10.60 K/µL). The basic metabolic panel, liver-associated enzymes, and lipase levels were within normal limits.

• What is your diagnosis?
• How would you treat this patient?
   

   

Our Diagnosis

Based on the clinical history of postprandial abdominal pain with prior cholecystectomy and leukocytosis, the initial differential diagnosis included peptic ulcer disease, gastroesophageal reflux, or delayed sequela of the cholecystectomy 6 months prior. Although suspicion remained for possible delayed postoperative complications from the cholecystectomy, ultrasound and hepatobiliary iminodiacetic acid (HIDA) scan were not pursued based on CT imaging findings. The needle-like hypodensity in the duodenum with surrounding inflammation visualized on CT was concerning for an unidentified penetrating foreign body with a possible retroperitoneal microperforation.

After these imaging findings were relayed from Radiology to the Gastroenterology Service, the patient underwent an upper gastrointestinal (GI) endoscopy to further evaluate the duodenum. Inspection revealed mild gastritis and a linear, clear piece of plastic with both ends firmly lodged within the mucosa from the distal duodenal bulb to the second portion of the duodenum; a significant mucosal defect of the bowel wall was visualized after careful extraction of the foreign body (Figure 2). The patient was diagnosed with a small duodenal perforation, which was sealed endoscopically with 2 endoclips. The extracted piece of plastic was examined and determined to be a broken cocktail pick (Figure 3). During discussion with the patient postprocedure, he stated that he ingested several olive martinis (which were served with cocktail picks) approximately 3 weeks prior to presentation and did not recall ingesting the cocktail pick. A repeat abdominal CT following the endoscopy demonstrated no leak or free air from the site of the repaired duodenal perforation (Figure 4). The patient avoided surgery and was permitted to resume a liquid diet prior to discharge.

Discussion

Foreign body ingestion in adults is most commonly unintentional with fish bones being the most common culprit.¹ In unintentional instances of foreign body ingestion, many patients are not aware of the event, with dentures posing a significant well-known risk factor due to lack of palatal sensory feedback.² Most ingested foreign bodies pass uninhibited through the GI tract without complications. However, less than 1% of ingested foreign bodies cause potentially life-threatening GI perforations.³

The risk of GI perforation due to foreign body ingestion is greatest with elongated, sharp objects, such as needles, bones, toothpicks, and cocktail picks. These objects tend to lodge at areas of narrowing or angulation, such as the appendix, ileocecal region, or as in this case, the duodenum.³ Passage of a foreign body through the duodenum is more likely to be inhibited if the object is longer than 6 cm and with a diameter > 2.5 cm.⁴ Signs of duodenal perforation are often subtle compared with jejunal or ileal perforations. Patients are commonly afebrile with normal white blood cell counts and are more likely to have chronic symptoms for > 3 days before the appropriate diagnosis of foreign body ingestion is made.¹ Duodenal perforations may be more stable clinically compared with distal GI perforations in part due to the retroperitoneal location with relatively fewer bacteria present intraluminally. GI perforations may not occur acutely during passage of the foreign body but can present weeks, months, or even years later.⁵ Delayed onset of symptoms may happen when the foreign body becomes lodged and only partially perforates the bowel wall, resulting in a chronic inflammatory process. Other possible complications include fistulization and abscess formation from migrating linear sharp objects through the bowel wall, which is most observed with toothpicks and cocktail picks, specifically.⁵

Foreign bodies identified on plain radiographs commonly include radiopaque objects, such as glass, metallic objects, most animal bones and some fish bones, and some medications. However, radiolucent objects, such as toothpicks and cocktail picks, wood, plastic, most fish bones, and most medicines, often will not appear on radiographs. The diagnosis of ingested foreign body can therefore easily be delayed or overlooked on plain radiographs due to ingestion of radiolucent objects or lack of adequate patient history. A high index of suspicion is needed in such instances. The modality of choice for identifying GI perforation due to ingested foreign objects is CT.⁵ All of these commonly missed materials on radiographs will be visible on CT with variable densities. As an added benefit, CT also may reveal ingested objects not visualized on radiographs and show ancillary signs of perforation, such as extraluminal free air, localized inflammation, and fluid collections or abscess surrounding a segment of thickened bowel.⁵

Most ingested foreign bodies will pass through the GI system and can be managed with careful observation alone. However, upper endoscopy is emergently indicated in 3 scenarios of foreign body ingestion: (1) complete occlusion of the esophagus with salivary pooling due to risk of aspiration; (2) ingestion of batteries due to toxic substances; and (3) ingestion of sharp or pointed foreign bodies due to risk of perforation.⁴ Overall, endoscopic intervention is required in 20% of cases and surgical intervention remains rare at 1%.⁴ In the case of this patient, an emergent upper endoscopy was needed due to suspected duodenal perforation.

Treatment of duodenal perforations due to foreign bodies may involve conservative, surgical, or endoscopic management. Contained, small perforations in a stable patient may be treated conservatively with IV fluids, antibiotics, and proton pump inhibitors as they self-seal with omentum if the foreign body has passed.⁶ Retained duodenal foreign bodies pose a risk of persistent perforation or fistulization and must be removed. Anterior duodenal perforations pose a risk of peritonitis, whereas posterior duodenal perforations, although retroperitoneal and sparing the peritoneal cavity, may result in localized abscess formation necessitating foreign body removal. Endoscopic clipping is a modernized, less invasive way to close GI perforations. Through-the-scope clips (TTSCs) can close luminal defects < 2 cm in size.⁷ Defects > 1 cm may be repaired with combined TTSCs and endoloop or omental patching. Over-the-scope clips can close full thickness defects up to 2 to 3 cm with the advantage of being able to close leaks and fistulas involving inflamed or indurated tissue.⁷

Conclusions

Intestinal perforations related to foreign body ingestion are a rare complication occurring in < 1% of patients. Although most ingested foreign objects will pass through the GI tract, elongated or sharp objects pose a risk for perforation. In many cases, a history of foreign body ingestion is not obtained, and a high index of suspicion is required. Duodenal perforations due to foreign body ingestion should be included in the differential among the more common diagnoses of peptic ulcers, pancreatitis, and gallbladder disease in the setting of postprandial right upper quadrant abdominal pain. CT is the best modality for identifying foreign bodies, including objects that may be missed on plain radiographs.

A patient with worsening chronic cough, shortness of breath, and hemoptysis tested negative for tuberculosis; but a chest computed tomography scan showed an upper left lobe cavitary lesion.

A 71-year-old, currently homeless male veteran with a 29 pack-year history of smoking and history of alcohol abuse presented to the emergency department at Washington DC Veterans Affairs Medical Center with worsening chronic cough and shortness of breath. He had no history of HIV or immunosuppressant medications. Four weeks prior, he was treated at an outpatient urgent care for community acquired pneumonia with a 10-day course of oral amoxicillin/clavulanic acid 875 mg twice daily and azithromycin 500 mg day 1, then 250 mg days 2 through 5. Despite antibiotic therapy, his symptoms continued to worsen, and he developed hemoptysis. He also reported weight loss of 20 lb in the past 3 months despite a strong appetite and adequate oral intake. He reported no fevers and night sweats. A review of the patient’s systems was otherwise unremarkable.

On examination, the patient was afebrile at 37.2 °C but tachycardic at 108 beats/min. He also was tachypneic at 22 breaths/min with an oxygen saturation of 89% on room air. Decreased breath sounds in the left upper lobe were noted on auscultation of the lung fields. Laboratory test results were notable for a leukocytosis of 14.3 k/μL (reference range, 4-11k/μL) and an elevated erythrocyte sedimentation rate (ESR) of 25.08 mm/h (reference range, 0-16 mm/h) and C-reactive protein (CRP) of 4.75 mg/L (reference range, 0.00-3.00 mg/L). Liver-associated enzymes and a coagulation panel were within normal limits. His QuantiFERON-TB Gold tuberculosis (TB) blood test was negative. A computed tomography (CT) scan of the chest was obtained, which showed an interval increase of a known upper left lobe cavitary lesion compared with that of prior imaging and the presence of a ball-shaped lesion in the cavity (Figures 1 and 2).

In addition to the imaging, the patient underwent bronchoscopy with bronchoalveolar lavage (BAL) to further evaluate the upper left lobe cavitary lesion. The differential diagnosis for pulmonary cavities is described in the Table. The BAL aspirates were negative for acid-fast bacteria; however, periodic acid–Schiff stain and Grocott methenamine silver stain showed fungal elements. He was diagnosed with chronic cavitary pulmonary aspergillosis (CCPA), confirmed with serum antigen (galactomannan assay) and serum immunoglobulin G (IgG) positive for Aspergillus fumigatus (A fumigatus). Mycologic cultures were positive for A fumigatus.

Discussion

Aspergillomas are accumulations of Aspergillus spp hyphae, fibrin, and other inflammatory components that typically occur in preexisting pulmonary cavities.¹ They are most frequently caused by A fumigatus, which is ubiquitous in the environment and acquired via inhalation of airborne spores in 90% of cases.² The typical ball-shaped appearance forms when hyphae growing along the inside walls of the cavity ultimately fall inward, usually leaving a surrounding pocket of air that can be seen on diagnostic imaging. CCPA falls within the chronic pulmonary aspergillosis (CPA) category, which includes a spectrum of other subtypes to include single aspergillomas, Aspergillus nodules, and chronic fibrosing pulmonary aspergillosis (CFPA). The prevalence of CPA and its subtypes are limited to case reports and case series in the literature, with reported rates differing up to 40-fold based on region, treatment, and diagnosis criteria.^3,4 Models developed by Denning and colleagues mirror those used by The World Health Organization and estimate 1.2 million people have CPA as a sequela to pulmonary TB globally.⁵

A single aspergilloma (simple aspergilloma) is typically not invasive, whereas CCPA (complex aspergilloma) is the most common CPA and can behave more invasively.^6,7 Both can occur in immunocompetent hosts. One study followed 140 individuals with aspergillomas for more than 7 years and found that 60.8% of aspergillomas remained stable in size, while 25.9% increased and 13.3% decreased in size. Half of cases were complicated by hemoptysis, but only 4.2% of cases became invasive.⁸ Roughly 70% of aspergillomas occur in individuals with a previous history of TB, but any pulmonary cavity can put a patient at increased risk.

Cases have been observed in patients with pulmonary cysts, emphysema/chronic obstructive pulmonary disease, bullae, lung cancer, sarcoidosis, other fungal cavities, and previous lung surgeries.⁹ Because of its association with CPA, TB testing should be completed as part of the workup as was the case in our patient. Although QuantiFERON-TB Gold has an estimated sensitivity of 92% per the manufacturer’s package insert, results can vary depending on the setting and extent of the TB.¹⁰

Clinical features of Aspergillus infection in immunocompetent individuals include weight loss, chronic nonproductive cough, hemoptysis of variable severity, fatigue, and/or shortness of breath.¹¹ CT is the imaging modality of choice and will typically show an upper-lobe cavitation with or without a fungal ball. For patients with suspicious imaging, laboratory testing with serum Aspergillus IgG antibodies should be performed. Aspergillus antigen testing is performed with galactomannan enzyme immunoassay, which detects galactomannan, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp. This should be performed on BAL washings rather than serum, however, as serum testing has poor sensitivity.¹¹ Sputum culture is not very sensitive, and although the polymerase chain reaction of sputum and BAL fluid are more sensitive than culture, false-positive results can occur with transient colonization or contamination of samples.^11,12 Elevations of inflammatory markers, namely ESR and CRP, are commonly present but not specific for CPA.

Denning and colleagues propose the following criteria for diagnosing CCPA: one large cavity or 2 or more cavities on chest imaging with or without a fungal ball (aspergilloma) in one or more of the cavities (exclude patients with other chronic fungal cavitary lesions, eg, pulmonary histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis); and at least one of the following symptoms for at least 3 months: fever, weight loss, fatigue, cough, sputum production, hemoptysis, or shortness of breath; and a positive Aspergillus IgG with or without culture of Aspergillus spp from the lungs.¹¹Our case fulfills the diagnostic criteria for CCPA. The ≥ 3 months of weight loss was useful in differentiating this case from a single aspergilloma in which the role of antifungal treatment remains unclear especially in those who are asymptomatic.² In those with single aspergillomas with significant hemoptysis, embolization may be required. In the management of localized CCPA, surgical excision is recommended and curative in many cases.^6,11 If left untreated, CCPA carries a 5-year mortality rate as high as 80% and often is accompanied with progression to CFPA, the terminal fibrosing evolution of CCPA, resulting in major fibrotic lung destruction.⁶ Oral azoles with or without surgical management also are useful in preventing clinical and radiologic progression.⁶

A multidisciplinary team, including infectious disease and surgery carefully discussed treatment options with the patient. Surgery was offered and the patient declined. We then decided on a trial of medical management alone based on shared decision making. In accordance with the recommendations from our infectious disease colleagues, the patient was started on a voriconazole 200 mg orally twice daily. Duration of therapy was planned for 6 months, with close monitoring of hepatic function, serum electrolytes, and visual function.¹³

Conclusions

This case highlights important differences among the CPA subtypes and how management differs based on etiology. Diagnostic criteria for CCPA were discussed, and in any patient with the constellation of the symptoms described with one or more cavitary lesions noted on imaging, CCPA should be considered regardless of immunocompetence. A multidisciplinary treatment approach with medical and surgical considerations is crucial to prevent progression to CFPA.

A patient with worsening chronic cough, shortness of breath, and hemoptysis tested negative for tuberculosis; but a chest computed tomography scan showed an upper left lobe cavitary lesion.

A 71-year-old, currently homeless male veteran with a 29 pack-year history of smoking and history of alcohol abuse presented to the emergency department at Washington DC Veterans Affairs Medical Center with worsening chronic cough and shortness of breath. He had no history of HIV or immunosuppressant medications. Four weeks prior, he was treated at an outpatient urgent care for community acquired pneumonia with a 10-day course of oral amoxicillin/clavulanic acid 875 mg twice daily and azithromycin 500 mg day 1, then 250 mg days 2 through 5. Despite antibiotic therapy, his symptoms continued to worsen, and he developed hemoptysis. He also reported weight loss of 20 lb in the past 3 months despite a strong appetite and adequate oral intake. He reported no fevers and night sweats. A review of the patient’s systems was otherwise unremarkable.

On examination, the patient was afebrile at 37.2 °C but tachycardic at 108 beats/min. He also was tachypneic at 22 breaths/min with an oxygen saturation of 89% on room air. Decreased breath sounds in the left upper lobe were noted on auscultation of the lung fields. Laboratory test results were notable for a leukocytosis of 14.3 k/μL (reference range, 4-11k/μL) and an elevated erythrocyte sedimentation rate (ESR) of 25.08 mm/h (reference range, 0-16 mm/h) and C-reactive protein (CRP) of 4.75 mg/L (reference range, 0.00-3.00 mg/L). Liver-associated enzymes and a coagulation panel were within normal limits. His QuantiFERON-TB Gold tuberculosis (TB) blood test was negative. A computed tomography (CT) scan of the chest was obtained, which showed an interval increase of a known upper left lobe cavitary lesion compared with that of prior imaging and the presence of a ball-shaped lesion in the cavity (Figures 1 and 2).

In addition to the imaging, the patient underwent bronchoscopy with bronchoalveolar lavage (BAL) to further evaluate the upper left lobe cavitary lesion. The differential diagnosis for pulmonary cavities is described in the Table. The BAL aspirates were negative for acid-fast bacteria; however, periodic acid–Schiff stain and Grocott methenamine silver stain showed fungal elements. He was diagnosed with chronic cavitary pulmonary aspergillosis (CCPA), confirmed with serum antigen (galactomannan assay) and serum immunoglobulin G (IgG) positive for Aspergillus fumigatus (A fumigatus). Mycologic cultures were positive for A fumigatus.

Discussion

Aspergillomas are accumulations of Aspergillus spp hyphae, fibrin, and other inflammatory components that typically occur in preexisting pulmonary cavities.¹ They are most frequently caused by A fumigatus, which is ubiquitous in the environment and acquired via inhalation of airborne spores in 90% of cases.² The typical ball-shaped appearance forms when hyphae growing along the inside walls of the cavity ultimately fall inward, usually leaving a surrounding pocket of air that can be seen on diagnostic imaging. CCPA falls within the chronic pulmonary aspergillosis (CPA) category, which includes a spectrum of other subtypes to include single aspergillomas, Aspergillus nodules, and chronic fibrosing pulmonary aspergillosis (CFPA). The prevalence of CPA and its subtypes are limited to case reports and case series in the literature, with reported rates differing up to 40-fold based on region, treatment, and diagnosis criteria.^3,4 Models developed by Denning and colleagues mirror those used by The World Health Organization and estimate 1.2 million people have CPA as a sequela to pulmonary TB globally.⁵

A single aspergilloma (simple aspergilloma) is typically not invasive, whereas CCPA (complex aspergilloma) is the most common CPA and can behave more invasively.^6,7 Both can occur in immunocompetent hosts. One study followed 140 individuals with aspergillomas for more than 7 years and found that 60.8% of aspergillomas remained stable in size, while 25.9% increased and 13.3% decreased in size. Half of cases were complicated by hemoptysis, but only 4.2% of cases became invasive.⁸ Roughly 70% of aspergillomas occur in individuals with a previous history of TB, but any pulmonary cavity can put a patient at increased risk.

Cases have been observed in patients with pulmonary cysts, emphysema/chronic obstructive pulmonary disease, bullae, lung cancer, sarcoidosis, other fungal cavities, and previous lung surgeries.⁹ Because of its association with CPA, TB testing should be completed as part of the workup as was the case in our patient. Although QuantiFERON-TB Gold has an estimated sensitivity of 92% per the manufacturer’s package insert, results can vary depending on the setting and extent of the TB.¹⁰

Clinical features of Aspergillus infection in immunocompetent individuals include weight loss, chronic nonproductive cough, hemoptysis of variable severity, fatigue, and/or shortness of breath.¹¹ CT is the imaging modality of choice and will typically show an upper-lobe cavitation with or without a fungal ball. For patients with suspicious imaging, laboratory testing with serum Aspergillus IgG antibodies should be performed. Aspergillus antigen testing is performed with galactomannan enzyme immunoassay, which detects galactomannan, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp. This should be performed on BAL washings rather than serum, however, as serum testing has poor sensitivity.¹¹ Sputum culture is not very sensitive, and although the polymerase chain reaction of sputum and BAL fluid are more sensitive than culture, false-positive results can occur with transient colonization or contamination of samples.^11,12 Elevations of inflammatory markers, namely ESR and CRP, are commonly present but not specific for CPA.

Denning and colleagues propose the following criteria for diagnosing CCPA: one large cavity or 2 or more cavities on chest imaging with or without a fungal ball (aspergilloma) in one or more of the cavities (exclude patients with other chronic fungal cavitary lesions, eg, pulmonary histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis); and at least one of the following symptoms for at least 3 months: fever, weight loss, fatigue, cough, sputum production, hemoptysis, or shortness of breath; and a positive Aspergillus IgG with or without culture of Aspergillus spp from the lungs.¹¹Our case fulfills the diagnostic criteria for CCPA. The ≥ 3 months of weight loss was useful in differentiating this case from a single aspergilloma in which the role of antifungal treatment remains unclear especially in those who are asymptomatic.² In those with single aspergillomas with significant hemoptysis, embolization may be required. In the management of localized CCPA, surgical excision is recommended and curative in many cases.^6,11 If left untreated, CCPA carries a 5-year mortality rate as high as 80% and often is accompanied with progression to CFPA, the terminal fibrosing evolution of CCPA, resulting in major fibrotic lung destruction.⁶ Oral azoles with or without surgical management also are useful in preventing clinical and radiologic progression.⁶

A multidisciplinary team, including infectious disease and surgery carefully discussed treatment options with the patient. Surgery was offered and the patient declined. We then decided on a trial of medical management alone based on shared decision making. In accordance with the recommendations from our infectious disease colleagues, the patient was started on a voriconazole 200 mg orally twice daily. Duration of therapy was planned for 6 months, with close monitoring of hepatic function, serum electrolytes, and visual function.¹³

Conclusions

This case highlights important differences among the CPA subtypes and how management differs based on etiology. Diagnostic criteria for CCPA were discussed, and in any patient with the constellation of the symptoms described with one or more cavitary lesions noted on imaging, CCPA should be considered regardless of immunocompetence. A multidisciplinary treatment approach with medical and surgical considerations is crucial to prevent progression to CFPA.

A patient with worsening chronic cough, shortness of breath, and hemoptysis tested negative for tuberculosis; but a chest computed tomography scan showed an upper left lobe cavitary lesion.

A 71-year-old, currently homeless male veteran with a 29 pack-year history of smoking and history of alcohol abuse presented to the emergency department at Washington DC Veterans Affairs Medical Center with worsening chronic cough and shortness of breath. He had no history of HIV or immunosuppressant medications. Four weeks prior, he was treated at an outpatient urgent care for community acquired pneumonia with a 10-day course of oral amoxicillin/clavulanic acid 875 mg twice daily and azithromycin 500 mg day 1, then 250 mg days 2 through 5. Despite antibiotic therapy, his symptoms continued to worsen, and he developed hemoptysis. He also reported weight loss of 20 lb in the past 3 months despite a strong appetite and adequate oral intake. He reported no fevers and night sweats. A review of the patient’s systems was otherwise unremarkable.

On examination, the patient was afebrile at 37.2 °C but tachycardic at 108 beats/min. He also was tachypneic at 22 breaths/min with an oxygen saturation of 89% on room air. Decreased breath sounds in the left upper lobe were noted on auscultation of the lung fields. Laboratory test results were notable for a leukocytosis of 14.3 k/μL (reference range, 4-11k/μL) and an elevated erythrocyte sedimentation rate (ESR) of 25.08 mm/h (reference range, 0-16 mm/h) and C-reactive protein (CRP) of 4.75 mg/L (reference range, 0.00-3.00 mg/L). Liver-associated enzymes and a coagulation panel were within normal limits. His QuantiFERON-TB Gold tuberculosis (TB) blood test was negative. A computed tomography (CT) scan of the chest was obtained, which showed an interval increase of a known upper left lobe cavitary lesion compared with that of prior imaging and the presence of a ball-shaped lesion in the cavity (Figures 1 and 2).

In addition to the imaging, the patient underwent bronchoscopy with bronchoalveolar lavage (BAL) to further evaluate the upper left lobe cavitary lesion. The differential diagnosis for pulmonary cavities is described in the Table. The BAL aspirates were negative for acid-fast bacteria; however, periodic acid–Schiff stain and Grocott methenamine silver stain showed fungal elements. He was diagnosed with chronic cavitary pulmonary aspergillosis (CCPA), confirmed with serum antigen (galactomannan assay) and serum immunoglobulin G (IgG) positive for Aspergillus fumigatus (A fumigatus). Mycologic cultures were positive for A fumigatus.

Discussion

Aspergillomas are accumulations of Aspergillus spp hyphae, fibrin, and other inflammatory components that typically occur in preexisting pulmonary cavities.¹ They are most frequently caused by A fumigatus, which is ubiquitous in the environment and acquired via inhalation of airborne spores in 90% of cases.² The typical ball-shaped appearance forms when hyphae growing along the inside walls of the cavity ultimately fall inward, usually leaving a surrounding pocket of air that can be seen on diagnostic imaging. CCPA falls within the chronic pulmonary aspergillosis (CPA) category, which includes a spectrum of other subtypes to include single aspergillomas, Aspergillus nodules, and chronic fibrosing pulmonary aspergillosis (CFPA). The prevalence of CPA and its subtypes are limited to case reports and case series in the literature, with reported rates differing up to 40-fold based on region, treatment, and diagnosis criteria.^3,4 Models developed by Denning and colleagues mirror those used by The World Health Organization and estimate 1.2 million people have CPA as a sequela to pulmonary TB globally.⁵

A single aspergilloma (simple aspergilloma) is typically not invasive, whereas CCPA (complex aspergilloma) is the most common CPA and can behave more invasively.^6,7 Both can occur in immunocompetent hosts. One study followed 140 individuals with aspergillomas for more than 7 years and found that 60.8% of aspergillomas remained stable in size, while 25.9% increased and 13.3% decreased in size. Half of cases were complicated by hemoptysis, but only 4.2% of cases became invasive.⁸ Roughly 70% of aspergillomas occur in individuals with a previous history of TB, but any pulmonary cavity can put a patient at increased risk.

Cases have been observed in patients with pulmonary cysts, emphysema/chronic obstructive pulmonary disease, bullae, lung cancer, sarcoidosis, other fungal cavities, and previous lung surgeries.⁹ Because of its association with CPA, TB testing should be completed as part of the workup as was the case in our patient. Although QuantiFERON-TB Gold has an estimated sensitivity of 92% per the manufacturer’s package insert, results can vary depending on the setting and extent of the TB.¹⁰

Clinical features of Aspergillus infection in immunocompetent individuals include weight loss, chronic nonproductive cough, hemoptysis of variable severity, fatigue, and/or shortness of breath.¹¹ CT is the imaging modality of choice and will typically show an upper-lobe cavitation with or without a fungal ball. For patients with suspicious imaging, laboratory testing with serum Aspergillus IgG antibodies should be performed. Aspergillus antigen testing is performed with galactomannan enzyme immunoassay, which detects galactomannan, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp. This should be performed on BAL washings rather than serum, however, as serum testing has poor sensitivity.¹¹ Sputum culture is not very sensitive, and although the polymerase chain reaction of sputum and BAL fluid are more sensitive than culture, false-positive results can occur with transient colonization or contamination of samples.^11,12 Elevations of inflammatory markers, namely ESR and CRP, are commonly present but not specific for CPA.

Denning and colleagues propose the following criteria for diagnosing CCPA: one large cavity or 2 or more cavities on chest imaging with or without a fungal ball (aspergilloma) in one or more of the cavities (exclude patients with other chronic fungal cavitary lesions, eg, pulmonary histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis); and at least one of the following symptoms for at least 3 months: fever, weight loss, fatigue, cough, sputum production, hemoptysis, or shortness of breath; and a positive Aspergillus IgG with or without culture of Aspergillus spp from the lungs.¹¹Our case fulfills the diagnostic criteria for CCPA. The ≥ 3 months of weight loss was useful in differentiating this case from a single aspergilloma in which the role of antifungal treatment remains unclear especially in those who are asymptomatic.² In those with single aspergillomas with significant hemoptysis, embolization may be required. In the management of localized CCPA, surgical excision is recommended and curative in many cases.^6,11 If left untreated, CCPA carries a 5-year mortality rate as high as 80% and often is accompanied with progression to CFPA, the terminal fibrosing evolution of CCPA, resulting in major fibrotic lung destruction.⁶ Oral azoles with or without surgical management also are useful in preventing clinical and radiologic progression.⁶

A multidisciplinary team, including infectious disease and surgery carefully discussed treatment options with the patient. Surgery was offered and the patient declined. We then decided on a trial of medical management alone based on shared decision making. In accordance with the recommendations from our infectious disease colleagues, the patient was started on a voriconazole 200 mg orally twice daily. Duration of therapy was planned for 6 months, with close monitoring of hepatic function, serum electrolytes, and visual function.¹³

Conclusions

This case highlights important differences among the CPA subtypes and how management differs based on etiology. Diagnostic criteria for CCPA were discussed, and in any patient with the constellation of the symptoms described with one or more cavitary lesions noted on imaging, CCPA should be considered regardless of immunocompetence. A multidisciplinary treatment approach with medical and surgical considerations is crucial to prevent progression to CFPA.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.