Case Reports

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely uncommon vascular disorder of unknown etiology, first described by Chan and colleagues in 1992.^1-3 Angiomyomatous hamartoma particularly involves inguinal and femoral lymph nodes, with few cases reported in the cervical, popliteal, and submandibular lymph nodes.¹ Angiomyomatous hamartoma can occasionally be associated with edema of the ipsilateral limb. To the authors’ knowledge, to date only 18 cases of AMH have been reported.⁴

Case Presentation

A 40-year-old white man started to have a left inguinal and scrotal pain along with left thigh swelling at age 22 while serving in the U.S. Army.

An abdominal Doppler ultrasound did not show any evidence of portal hypertension. A thoraco-abdomino-pelvic computed tomography (CT) scan showed bilateral axillary, subcarinal (Figure 1), mesenteric and retroperitoneal (Figure 2), and left inguinal (Figure 3) lymphadenopathy. Excisional biopsy of a 3.5 x 2.5 x 1.5 cm left inguinal lymph node was performed, and histopathology showed extensive smooth muscle and vascular proliferation replacing most of the lymph node (Figure 4), a finding consistent with AMH. A trichrome staining (Figure 5) and immunohistochemical study for smooth muscle actin (Figure 6) were performed and supported the diagnosis. Due to persistent pain in the scrotal area, the patient underwent a left spermatic cord denervation. Currently, the patient has persistent left thigh swelling. His condition remains stable with a regular follow-up CT scan showing unchanged lymphadenopathy.

Discussion

Angiomyomatous hamartoma is a rare, primary vascular tumor of the lymph nodes occurring almost exclusively in the inguinal and femoral lymph nodes and occasionally associated with edema of the ipsilateral limb.¹ A few cases with popliteal and cervical lymph node involvement have been reported.¹ There are no prior reports of cases with either generalized adenopathy or hepatosplenomegaly.

The histopathogenesis of AMH remains unclear. Chan and colleagues first reported this distinct clinicopathologic entity in 1992 as a primary vascular tumor of the lymph node.^1-3 The hamartomatous nature of the disease was postulated by the authors on the basis of a disorganized growth pattern of smooth muscle cells and blood vessels noted on pathology.^2,3 The AMH could represent a localized malformation in a congenitally damaged lymphatic vessel system.⁵ Other hypothesis suggests lymphedema as a possible etiology of AMH through continuous stimulation of lymphatic vessels, which triggers vasoproliferation and eventually the vascular transformation of the lymph nodes.⁵

Differential diagnoses of AMH include nodal lymphangiomyomatosis, which is most prevalent in women, particularly presenting with thoracic and intra-abdominal lymph nodes and plumper HMB45 (human melanoma black 45) -positive tumor cells⁶; leiomyomato

Treatment is either conservative or surgical, depending on clinical judgment. This is only the 19th case of AMH reported so far in the literature and the fifth reported case in which the patient presented with ipsilateral lymphedema of the limb. Importantly, it is the first reported case with generalized (axillary, subcarinal, mesenteric, inguinal and retroperitoneal) lymphadenopathy and unexplained hepatosplenomegaly.

Conclusion

Angiomyomatous hamartoma of the lymph nodes is an exceedingly rare diagnosis but should be considered when evaluating patients with lymphatic tumors. This patient remains relatively asymptomatic and on observation at this time and seems to have more extensive disease than prior reports in the literature.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely uncommon vascular disorder of unknown etiology, first described by Chan and colleagues in 1992.^1-3 Angiomyomatous hamartoma particularly involves inguinal and femoral lymph nodes, with few cases reported in the cervical, popliteal, and submandibular lymph nodes.¹ Angiomyomatous hamartoma can occasionally be associated with edema of the ipsilateral limb. To the authors’ knowledge, to date only 18 cases of AMH have been reported.⁴

Case Presentation

A 40-year-old white man started to have a left inguinal and scrotal pain along with left thigh swelling at age 22 while serving in the U.S. Army.

An abdominal Doppler ultrasound did not show any evidence of portal hypertension. A thoraco-abdomino-pelvic computed tomography (CT) scan showed bilateral axillary, subcarinal (Figure 1), mesenteric and retroperitoneal (Figure 2), and left inguinal (Figure 3) lymphadenopathy. Excisional biopsy of a 3.5 x 2.5 x 1.5 cm left inguinal lymph node was performed, and histopathology showed extensive smooth muscle and vascular proliferation replacing most of the lymph node (Figure 4), a finding consistent with AMH. A trichrome staining (Figure 5) and immunohistochemical study for smooth muscle actin (Figure 6) were performed and supported the diagnosis. Due to persistent pain in the scrotal area, the patient underwent a left spermatic cord denervation. Currently, the patient has persistent left thigh swelling. His condition remains stable with a regular follow-up CT scan showing unchanged lymphadenopathy.

Discussion

Angiomyomatous hamartoma is a rare, primary vascular tumor of the lymph nodes occurring almost exclusively in the inguinal and femoral lymph nodes and occasionally associated with edema of the ipsilateral limb.¹ A few cases with popliteal and cervical lymph node involvement have been reported.¹ There are no prior reports of cases with either generalized adenopathy or hepatosplenomegaly.

The histopathogenesis of AMH remains unclear. Chan and colleagues first reported this distinct clinicopathologic entity in 1992 as a primary vascular tumor of the lymph node.^1-3 The hamartomatous nature of the disease was postulated by the authors on the basis of a disorganized growth pattern of smooth muscle cells and blood vessels noted on pathology.^2,3 The AMH could represent a localized malformation in a congenitally damaged lymphatic vessel system.⁵ Other hypothesis suggests lymphedema as a possible etiology of AMH through continuous stimulation of lymphatic vessels, which triggers vasoproliferation and eventually the vascular transformation of the lymph nodes.⁵

Differential diagnoses of AMH include nodal lymphangiomyomatosis, which is most prevalent in women, particularly presenting with thoracic and intra-abdominal lymph nodes and plumper HMB45 (human melanoma black 45) -positive tumor cells⁶; leiomyomato

Treatment is either conservative or surgical, depending on clinical judgment. This is only the 19th case of AMH reported so far in the literature and the fifth reported case in which the patient presented with ipsilateral lymphedema of the limb. Importantly, it is the first reported case with generalized (axillary, subcarinal, mesenteric, inguinal and retroperitoneal) lymphadenopathy and unexplained hepatosplenomegaly.

Conclusion

Angiomyomatous hamartoma of the lymph nodes is an exceedingly rare diagnosis but should be considered when evaluating patients with lymphatic tumors. This patient remains relatively asymptomatic and on observation at this time and seems to have more extensive disease than prior reports in the literature.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely uncommon vascular disorder of unknown etiology, first described by Chan and colleagues in 1992.^1-3 Angiomyomatous hamartoma particularly involves inguinal and femoral lymph nodes, with few cases reported in the cervical, popliteal, and submandibular lymph nodes.¹ Angiomyomatous hamartoma can occasionally be associated with edema of the ipsilateral limb. To the authors’ knowledge, to date only 18 cases of AMH have been reported.⁴

Case Presentation

A 40-year-old white man started to have a left inguinal and scrotal pain along with left thigh swelling at age 22 while serving in the U.S. Army.

An abdominal Doppler ultrasound did not show any evidence of portal hypertension. A thoraco-abdomino-pelvic computed tomography (CT) scan showed bilateral axillary, subcarinal (Figure 1), mesenteric and retroperitoneal (Figure 2), and left inguinal (Figure 3) lymphadenopathy. Excisional biopsy of a 3.5 x 2.5 x 1.5 cm left inguinal lymph node was performed, and histopathology showed extensive smooth muscle and vascular proliferation replacing most of the lymph node (Figure 4), a finding consistent with AMH. A trichrome staining (Figure 5) and immunohistochemical study for smooth muscle actin (Figure 6) were performed and supported the diagnosis. Due to persistent pain in the scrotal area, the patient underwent a left spermatic cord denervation. Currently, the patient has persistent left thigh swelling. His condition remains stable with a regular follow-up CT scan showing unchanged lymphadenopathy.

Discussion

Angiomyomatous hamartoma is a rare, primary vascular tumor of the lymph nodes occurring almost exclusively in the inguinal and femoral lymph nodes and occasionally associated with edema of the ipsilateral limb.¹ A few cases with popliteal and cervical lymph node involvement have been reported.¹ There are no prior reports of cases with either generalized adenopathy or hepatosplenomegaly.

The histopathogenesis of AMH remains unclear. Chan and colleagues first reported this distinct clinicopathologic entity in 1992 as a primary vascular tumor of the lymph node.^1-3 The hamartomatous nature of the disease was postulated by the authors on the basis of a disorganized growth pattern of smooth muscle cells and blood vessels noted on pathology.^2,3 The AMH could represent a localized malformation in a congenitally damaged lymphatic vessel system.⁵ Other hypothesis suggests lymphedema as a possible etiology of AMH through continuous stimulation of lymphatic vessels, which triggers vasoproliferation and eventually the vascular transformation of the lymph nodes.⁵

Differential diagnoses of AMH include nodal lymphangiomyomatosis, which is most prevalent in women, particularly presenting with thoracic and intra-abdominal lymph nodes and plumper HMB45 (human melanoma black 45) -positive tumor cells⁶; leiomyomato

Treatment is either conservative or surgical, depending on clinical judgment. This is only the 19th case of AMH reported so far in the literature and the fifth reported case in which the patient presented with ipsilateral lymphedema of the limb. Importantly, it is the first reported case with generalized (axillary, subcarinal, mesenteric, inguinal and retroperitoneal) lymphadenopathy and unexplained hepatosplenomegaly.

Conclusion

Angiomyomatous hamartoma of the lymph nodes is an exceedingly rare diagnosis but should be considered when evaluating patients with lymphatic tumors. This patient remains relatively asymptomatic and on observation at this time and seems to have more extensive disease than prior reports in the literature.

Septic arthritis predominantly involves the weight-bearing joints of the hip and knee, which account for nearly 60% of cases.¹ In contrast, the shoulder joint is involved in 10% to 15% of cases, though this number may be higher among intravenous (IV) drug users.² The most common causative organisms are the Staphylococcus species, followed closely by β-hemolytic streptococci, with these 2 groups accounting for more than 90% of all cases.³ The Streptococcus viridans group belongs to normal oral flora residing predominantly on the surface of teeth. Although well known for its ability to colonize heart valves and frequently cause bacterial endocarditis, this group has rarely been associated with septic arthritis. Furthermore, Streptococcus mitis, a subgroup of S viridans, has been implicated even less commonly.

In this article, we report a case of glenohumeral joint septic arthritis caused by S mitis. To our knowledge, such a case has not been previously reported in the English literature. Given the low virulence of this orally based bacterium, treating physicians must maintain clinical suspicion for the organism in the setting of persistent joint effusion and pain in association with periodontal disease or trauma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A right-hand-dominant 54-year-old man presented to Dr. Gruson with complaints of persistent right shoulder pain associated with worsening range of motion (ROM). Three weeks earlier, the patient reported being assaulted and noted progressive swelling about the right shoulder. He denied fevers, chills, or prior shoulder problems. Although his past medical history was remarkable for hepatitis C and diabetes, he was not taking any diabetic medications at that time. A review of systems was remarkable for poor dental hygiene, and the patient was missing several teeth, which he said had been knocked out during the assault. Physical examination revealed diffuse tenderness about the right shoulder and severe pain with all passive movement. The shoulder was pseudoparalyzed. There were no subcutaneous collections, wounds, or ecchymosis about the shoulder. Mild calor was noted on the right shoulder relative to the left. Radiographs of the right shoulder showed no acute osseous abnormalities.

Magnetic resonance imaging (MRI), which was urgently obtained to assess the integrity of the rotator cuff and the location of the effusion, showed a large subacromial and glenohumeral joint effusion as well as diffuse muscular edema (Figures 1A-1C).

Discussion

Staphylococcus aureus is the leading causative organism of septic arthritis, accounting for more than 60% of all cases.⁴ Conversely, the Streptococcus viridans group is rarely implicated in septic arthritis, accounting for <1% of cases.⁴S viridans is part of the commensal oral flora and has low virulence. This heterogeneous group is subdivided into S mitis, S salivarius, S anginosus, S mutans, and S bovis. The S mitis group is further subdivided into S sanguinis (formerly known as S sanguis) and S mitis. Infection by an organism of the S viridans group usually occurs on a previously injured focus, and the organism is a causative agent of bacterial endocarditis.⁵ Reported cases of septic arthritis caused by S viridans have predominantly involved the knee joint—with severe osteoarthritis, poor dental hygiene, and prior IV drug use identified as risk factors.^5-7The shoulder joint is seldom involved in septic arthritis; estimated incidence is under 8%.⁸ Although overall incidence may rise in an increasingly elderly patient population, incidence of shoulder infection remains low.^2,9

The main routes for developing septic arthritis include direct inoculation secondary to penetrating trauma or hematologic spread.¹⁰ Coatsworth and colleagues¹¹ reported on iatrogenic S mitis septic arthritis of a shoulder arthroplasty during ultrasonography-guided aspiration by a technician who was not wearing a mask. Our institutional policy is to perform joint aspiration under strictly sterile conditions, which were adhered to in the present case. We surmise our patient developed transient bacteremia from the loss of several teeth, particularly given his poor dentition. Yombi and colleagues⁵ documented 2 cases of septic arthritis caused by Streptococcus gordonii, a relative of S sanguinis. One involved a previously replaced knee, and the other a native knee joint. Other cases of S viridans group septic arthritis have involved the knee,^6,7,12,13 the sternoclavicular joint,^14-16 and the acromioclavicular joint.¹⁷S sanguinis^6,7,12,15,16 and S gordonii⁵ have been implicated in most cases, and an unspeciated S viridans in others.^13,14,17 Concomitant periodontal disease has been reported in most cases as well,^6,7,12,15 including our patient’s case. In the English-language literature, we found no other reports of S mitis as the causative agent of acute septic glenohumeral joint arthritis from hematogenous spread.

There should be no delay in diagnosing septic arthritis, and infected material should be removed from the joint. In animal models, complete joint destruction occurred only 5 weeks after inoculation with Staphylococcus aureus.¹⁰ Garofalo and colleagues¹⁸ reported a trend toward improved functional outcomes after earlier operative treatment. The choice of open surgical drainage vs repeat needle aspiration seems to be of little consequence, as both have good long-term outcomes, but open surgical drainage seems to result in better long-term functional ROM.^2,9 However, results of a recent study suggested surgical treatment is not always superior to medical treatment for septic arthritis in native joints.¹⁹ In some cases involving S viridans species, treatment consisted of a combination of IV antibiotics and onetime or repeat aspiration;^6,12-15 treatment in the remaining cases was surgical débridement.^5,7,16,17 Given that S viridans is associated with bacterial endocarditis, echocardiography is essential if this organism is to be identified. Medical management and antibiotic treatment should be initiated after consultation with medical and infectious disease specialists.¹⁹We have reported a case of septic shoulder caused by S mitis, a low-virulence organism seldom associated with joint infection. The patient’s infection likely resulted from hematogenous spread from the oral cavity (dentition was poor). Urgent aspiration of the joint and baseline infection laboratory tests are recommended. MRI of the shoulder may show an effusion. Urgent arthroscopic irrigation and débridement can yield good clinical outcomes.

Am J Orthop. 2016;45(6):E343-E346. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Septic arthritis predominantly involves the weight-bearing joints of the hip and knee, which account for nearly 60% of cases.¹ In contrast, the shoulder joint is involved in 10% to 15% of cases, though this number may be higher among intravenous (IV) drug users.² The most common causative organisms are the Staphylococcus species, followed closely by β-hemolytic streptococci, with these 2 groups accounting for more than 90% of all cases.³ The Streptococcus viridans group belongs to normal oral flora residing predominantly on the surface of teeth. Although well known for its ability to colonize heart valves and frequently cause bacterial endocarditis, this group has rarely been associated with septic arthritis. Furthermore, Streptococcus mitis, a subgroup of S viridans, has been implicated even less commonly.

In this article, we report a case of glenohumeral joint septic arthritis caused by S mitis. To our knowledge, such a case has not been previously reported in the English literature. Given the low virulence of this orally based bacterium, treating physicians must maintain clinical suspicion for the organism in the setting of persistent joint effusion and pain in association with periodontal disease or trauma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A right-hand-dominant 54-year-old man presented to Dr. Gruson with complaints of persistent right shoulder pain associated with worsening range of motion (ROM). Three weeks earlier, the patient reported being assaulted and noted progressive swelling about the right shoulder. He denied fevers, chills, or prior shoulder problems. Although his past medical history was remarkable for hepatitis C and diabetes, he was not taking any diabetic medications at that time. A review of systems was remarkable for poor dental hygiene, and the patient was missing several teeth, which he said had been knocked out during the assault. Physical examination revealed diffuse tenderness about the right shoulder and severe pain with all passive movement. The shoulder was pseudoparalyzed. There were no subcutaneous collections, wounds, or ecchymosis about the shoulder. Mild calor was noted on the right shoulder relative to the left. Radiographs of the right shoulder showed no acute osseous abnormalities.

Magnetic resonance imaging (MRI), which was urgently obtained to assess the integrity of the rotator cuff and the location of the effusion, showed a large subacromial and glenohumeral joint effusion as well as diffuse muscular edema (Figures 1A-1C).

Discussion

Staphylococcus aureus is the leading causative organism of septic arthritis, accounting for more than 60% of all cases.⁴ Conversely, the Streptococcus viridans group is rarely implicated in septic arthritis, accounting for <1% of cases.⁴S viridans is part of the commensal oral flora and has low virulence. This heterogeneous group is subdivided into S mitis, S salivarius, S anginosus, S mutans, and S bovis. The S mitis group is further subdivided into S sanguinis (formerly known as S sanguis) and S mitis. Infection by an organism of the S viridans group usually occurs on a previously injured focus, and the organism is a causative agent of bacterial endocarditis.⁵ Reported cases of septic arthritis caused by S viridans have predominantly involved the knee joint—with severe osteoarthritis, poor dental hygiene, and prior IV drug use identified as risk factors.^5-7The shoulder joint is seldom involved in septic arthritis; estimated incidence is under 8%.⁸ Although overall incidence may rise in an increasingly elderly patient population, incidence of shoulder infection remains low.^2,9

The main routes for developing septic arthritis include direct inoculation secondary to penetrating trauma or hematologic spread.¹⁰ Coatsworth and colleagues¹¹ reported on iatrogenic S mitis septic arthritis of a shoulder arthroplasty during ultrasonography-guided aspiration by a technician who was not wearing a mask. Our institutional policy is to perform joint aspiration under strictly sterile conditions, which were adhered to in the present case. We surmise our patient developed transient bacteremia from the loss of several teeth, particularly given his poor dentition. Yombi and colleagues⁵ documented 2 cases of septic arthritis caused by Streptococcus gordonii, a relative of S sanguinis. One involved a previously replaced knee, and the other a native knee joint. Other cases of S viridans group septic arthritis have involved the knee,^6,7,12,13 the sternoclavicular joint,^14-16 and the acromioclavicular joint.¹⁷S sanguinis^6,7,12,15,16 and S gordonii⁵ have been implicated in most cases, and an unspeciated S viridans in others.^13,14,17 Concomitant periodontal disease has been reported in most cases as well,^6,7,12,15 including our patient’s case. In the English-language literature, we found no other reports of S mitis as the causative agent of acute septic glenohumeral joint arthritis from hematogenous spread.

There should be no delay in diagnosing septic arthritis, and infected material should be removed from the joint. In animal models, complete joint destruction occurred only 5 weeks after inoculation with Staphylococcus aureus.¹⁰ Garofalo and colleagues¹⁸ reported a trend toward improved functional outcomes after earlier operative treatment. The choice of open surgical drainage vs repeat needle aspiration seems to be of little consequence, as both have good long-term outcomes, but open surgical drainage seems to result in better long-term functional ROM.^2,9 However, results of a recent study suggested surgical treatment is not always superior to medical treatment for septic arthritis in native joints.¹⁹ In some cases involving S viridans species, treatment consisted of a combination of IV antibiotics and onetime or repeat aspiration;^6,12-15 treatment in the remaining cases was surgical débridement.^5,7,16,17 Given that S viridans is associated with bacterial endocarditis, echocardiography is essential if this organism is to be identified. Medical management and antibiotic treatment should be initiated after consultation with medical and infectious disease specialists.¹⁹We have reported a case of septic shoulder caused by S mitis, a low-virulence organism seldom associated with joint infection. The patient’s infection likely resulted from hematogenous spread from the oral cavity (dentition was poor). Urgent aspiration of the joint and baseline infection laboratory tests are recommended. MRI of the shoulder may show an effusion. Urgent arthroscopic irrigation and débridement can yield good clinical outcomes.

Am J Orthop. 2016;45(6):E343-E346. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Septic arthritis predominantly involves the weight-bearing joints of the hip and knee, which account for nearly 60% of cases.¹ In contrast, the shoulder joint is involved in 10% to 15% of cases, though this number may be higher among intravenous (IV) drug users.² The most common causative organisms are the Staphylococcus species, followed closely by β-hemolytic streptococci, with these 2 groups accounting for more than 90% of all cases.³ The Streptococcus viridans group belongs to normal oral flora residing predominantly on the surface of teeth. Although well known for its ability to colonize heart valves and frequently cause bacterial endocarditis, this group has rarely been associated with septic arthritis. Furthermore, Streptococcus mitis, a subgroup of S viridans, has been implicated even less commonly.

In this article, we report a case of glenohumeral joint septic arthritis caused by S mitis. To our knowledge, such a case has not been previously reported in the English literature. Given the low virulence of this orally based bacterium, treating physicians must maintain clinical suspicion for the organism in the setting of persistent joint effusion and pain in association with periodontal disease or trauma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A right-hand-dominant 54-year-old man presented to Dr. Gruson with complaints of persistent right shoulder pain associated with worsening range of motion (ROM). Three weeks earlier, the patient reported being assaulted and noted progressive swelling about the right shoulder. He denied fevers, chills, or prior shoulder problems. Although his past medical history was remarkable for hepatitis C and diabetes, he was not taking any diabetic medications at that time. A review of systems was remarkable for poor dental hygiene, and the patient was missing several teeth, which he said had been knocked out during the assault. Physical examination revealed diffuse tenderness about the right shoulder and severe pain with all passive movement. The shoulder was pseudoparalyzed. There were no subcutaneous collections, wounds, or ecchymosis about the shoulder. Mild calor was noted on the right shoulder relative to the left. Radiographs of the right shoulder showed no acute osseous abnormalities.

Magnetic resonance imaging (MRI), which was urgently obtained to assess the integrity of the rotator cuff and the location of the effusion, showed a large subacromial and glenohumeral joint effusion as well as diffuse muscular edema (Figures 1A-1C).

Discussion

Staphylococcus aureus is the leading causative organism of septic arthritis, accounting for more than 60% of all cases.⁴ Conversely, the Streptococcus viridans group is rarely implicated in septic arthritis, accounting for <1% of cases.⁴S viridans is part of the commensal oral flora and has low virulence. This heterogeneous group is subdivided into S mitis, S salivarius, S anginosus, S mutans, and S bovis. The S mitis group is further subdivided into S sanguinis (formerly known as S sanguis) and S mitis. Infection by an organism of the S viridans group usually occurs on a previously injured focus, and the organism is a causative agent of bacterial endocarditis.⁵ Reported cases of septic arthritis caused by S viridans have predominantly involved the knee joint—with severe osteoarthritis, poor dental hygiene, and prior IV drug use identified as risk factors.^5-7The shoulder joint is seldom involved in septic arthritis; estimated incidence is under 8%.⁸ Although overall incidence may rise in an increasingly elderly patient population, incidence of shoulder infection remains low.^2,9

The main routes for developing septic arthritis include direct inoculation secondary to penetrating trauma or hematologic spread.¹⁰ Coatsworth and colleagues¹¹ reported on iatrogenic S mitis septic arthritis of a shoulder arthroplasty during ultrasonography-guided aspiration by a technician who was not wearing a mask. Our institutional policy is to perform joint aspiration under strictly sterile conditions, which were adhered to in the present case. We surmise our patient developed transient bacteremia from the loss of several teeth, particularly given his poor dentition. Yombi and colleagues⁵ documented 2 cases of septic arthritis caused by Streptococcus gordonii, a relative of S sanguinis. One involved a previously replaced knee, and the other a native knee joint. Other cases of S viridans group septic arthritis have involved the knee,^6,7,12,13 the sternoclavicular joint,^14-16 and the acromioclavicular joint.¹⁷S sanguinis^6,7,12,15,16 and S gordonii⁵ have been implicated in most cases, and an unspeciated S viridans in others.^13,14,17 Concomitant periodontal disease has been reported in most cases as well,^6,7,12,15 including our patient’s case. In the English-language literature, we found no other reports of S mitis as the causative agent of acute septic glenohumeral joint arthritis from hematogenous spread.

There should be no delay in diagnosing septic arthritis, and infected material should be removed from the joint. In animal models, complete joint destruction occurred only 5 weeks after inoculation with Staphylococcus aureus.¹⁰ Garofalo and colleagues¹⁸ reported a trend toward improved functional outcomes after earlier operative treatment. The choice of open surgical drainage vs repeat needle aspiration seems to be of little consequence, as both have good long-term outcomes, but open surgical drainage seems to result in better long-term functional ROM.^2,9 However, results of a recent study suggested surgical treatment is not always superior to medical treatment for septic arthritis in native joints.¹⁹ In some cases involving S viridans species, treatment consisted of a combination of IV antibiotics and onetime or repeat aspiration;^6,12-15 treatment in the remaining cases was surgical débridement.^5,7,16,17 Given that S viridans is associated with bacterial endocarditis, echocardiography is essential if this organism is to be identified. Medical management and antibiotic treatment should be initiated after consultation with medical and infectious disease specialists.¹⁹We have reported a case of septic shoulder caused by S mitis, a low-virulence organism seldom associated with joint infection. The patient’s infection likely resulted from hematogenous spread from the oral cavity (dentition was poor). Urgent aspiration of the joint and baseline infection laboratory tests are recommended. MRI of the shoulder may show an effusion. Urgent arthroscopic irrigation and débridement can yield good clinical outcomes.

Am J Orthop. 2016;45(6):E343-E346. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

Unilateral inferior shoulder dislocation (luxatio erecta) is uncommon, accounting for only 0.5% of all shoulder dislocations.¹ Bilateral luxatio erecta is extremely rare, having been described fewer than 20 times in the literature. The most common etiology is hyperabduction causing the humerus to lever on the acromion; less common is axial loading onto a fully abducted arm and an extended elbow.² Hyperabduction can occur when a person grabs an object in an attempt to stop a fall, as occurred in the present case. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 58-year-old man with a trauma injury presented to our emergency department. For his open right elbow fracture, emergency medical services had given him fentanyl en route, and when he arrived he was less responsive. As the patient reported, he had been on a scaffold 16 feet high when it began to give way. He jumped for another scaffold, 3 to 4 feet away, but came up short and, in an attempt to stop himself from falling, grabbed onto it with arms extended and above his head. His hands and arms were immediately pulled up in full extension. When both shoulders became dislocated, he could not hold on and fell to the ground, landing on a buttock. He did not lose consciousness.

Physical examination revealed both arms abducted at the shoulder, and elbows extended (Figure 1).

Discussion

Although inferior shoulder dislocations are rare, they carry a higher rate of complications, most of which our patient experienced. Our patient had bilateral humeral head fractures, which occur in 80% of cases.⁶ Postreduction CT showed the degree of his fractures (Figure 3).

Our patient also had reduced sensation in the axillary nerve distribution, which occurs in 60% of inferior dislocations.⁶ Axillary nerve injuries produce numbness in the lateral arm or posterior shoulder and weakness with shoulder flexion, abduction, and external rotation.⁷ In our patient’s case, sensation returned after reduction, which is typical (most patients have a positive prognosis).⁸ As the shoulder dislocates inferiorly, the humeral head tears the glenohumeral capsule inferiorly, which can damage the axillary artery. This artery becomes the brachial and eventually the radial and ulnar arteries, which can have decreased or absent pulses with injury.

Inferior dislocations are also associated with abundant soft-tissue injuries, including torn rotator cuff, shoulder capsule avulsion, and disruption of adjacent muscles (supraspinatus, infraspinatus, teres minor, subscapularis, pectoralis major).⁹Luxatio erecta is relatively easy to diagnose given the unmistakable arm positioning. The key for the physician is first to assess for the many possible complications, then to administer the proper sedation and analgesia for reduction, and finally to reassess for complications.

Am J Orthop. 2016;45(6):E328-E330. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Unilateral inferior shoulder dislocation (luxatio erecta) is uncommon, accounting for only 0.5% of all shoulder dislocations.¹ Bilateral luxatio erecta is extremely rare, having been described fewer than 20 times in the literature. The most common etiology is hyperabduction causing the humerus to lever on the acromion; less common is axial loading onto a fully abducted arm and an extended elbow.² Hyperabduction can occur when a person grabs an object in an attempt to stop a fall, as occurred in the present case. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 58-year-old man with a trauma injury presented to our emergency department. For his open right elbow fracture, emergency medical services had given him fentanyl en route, and when he arrived he was less responsive. As the patient reported, he had been on a scaffold 16 feet high when it began to give way. He jumped for another scaffold, 3 to 4 feet away, but came up short and, in an attempt to stop himself from falling, grabbed onto it with arms extended and above his head. His hands and arms were immediately pulled up in full extension. When both shoulders became dislocated, he could not hold on and fell to the ground, landing on a buttock. He did not lose consciousness.

Physical examination revealed both arms abducted at the shoulder, and elbows extended (Figure 1).

Discussion

Although inferior shoulder dislocations are rare, they carry a higher rate of complications, most of which our patient experienced. Our patient had bilateral humeral head fractures, which occur in 80% of cases.⁶ Postreduction CT showed the degree of his fractures (Figure 3).

Our patient also had reduced sensation in the axillary nerve distribution, which occurs in 60% of inferior dislocations.⁶ Axillary nerve injuries produce numbness in the lateral arm or posterior shoulder and weakness with shoulder flexion, abduction, and external rotation.⁷ In our patient’s case, sensation returned after reduction, which is typical (most patients have a positive prognosis).⁸ As the shoulder dislocates inferiorly, the humeral head tears the glenohumeral capsule inferiorly, which can damage the axillary artery. This artery becomes the brachial and eventually the radial and ulnar arteries, which can have decreased or absent pulses with injury.

Inferior dislocations are also associated with abundant soft-tissue injuries, including torn rotator cuff, shoulder capsule avulsion, and disruption of adjacent muscles (supraspinatus, infraspinatus, teres minor, subscapularis, pectoralis major).⁹Luxatio erecta is relatively easy to diagnose given the unmistakable arm positioning. The key for the physician is first to assess for the many possible complications, then to administer the proper sedation and analgesia for reduction, and finally to reassess for complications.

Am J Orthop. 2016;45(6):E328-E330. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Unilateral inferior shoulder dislocation (luxatio erecta) is uncommon, accounting for only 0.5% of all shoulder dislocations.¹ Bilateral luxatio erecta is extremely rare, having been described fewer than 20 times in the literature. The most common etiology is hyperabduction causing the humerus to lever on the acromion; less common is axial loading onto a fully abducted arm and an extended elbow.² Hyperabduction can occur when a person grabs an object in an attempt to stop a fall, as occurred in the present case. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 58-year-old man with a trauma injury presented to our emergency department. For his open right elbow fracture, emergency medical services had given him fentanyl en route, and when he arrived he was less responsive. As the patient reported, he had been on a scaffold 16 feet high when it began to give way. He jumped for another scaffold, 3 to 4 feet away, but came up short and, in an attempt to stop himself from falling, grabbed onto it with arms extended and above his head. His hands and arms were immediately pulled up in full extension. When both shoulders became dislocated, he could not hold on and fell to the ground, landing on a buttock. He did not lose consciousness.

Physical examination revealed both arms abducted at the shoulder, and elbows extended (Figure 1).

Discussion

Although inferior shoulder dislocations are rare, they carry a higher rate of complications, most of which our patient experienced. Our patient had bilateral humeral head fractures, which occur in 80% of cases.⁶ Postreduction CT showed the degree of his fractures (Figure 3).

Our patient also had reduced sensation in the axillary nerve distribution, which occurs in 60% of inferior dislocations.⁶ Axillary nerve injuries produce numbness in the lateral arm or posterior shoulder and weakness with shoulder flexion, abduction, and external rotation.⁷ In our patient’s case, sensation returned after reduction, which is typical (most patients have a positive prognosis).⁸ As the shoulder dislocates inferiorly, the humeral head tears the glenohumeral capsule inferiorly, which can damage the axillary artery. This artery becomes the brachial and eventually the radial and ulnar arteries, which can have decreased or absent pulses with injury.

Inferior dislocations are also associated with abundant soft-tissue injuries, including torn rotator cuff, shoulder capsule avulsion, and disruption of adjacent muscles (supraspinatus, infraspinatus, teres minor, subscapularis, pectoralis major).⁹Luxatio erecta is relatively easy to diagnose given the unmistakable arm positioning. The key for the physician is first to assess for the many possible complications, then to administer the proper sedation and analgesia for reduction, and finally to reassess for complications.

Am J Orthop. 2016;45(6):E328-E330. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Although intrauterine devices (IUDs) are a mainstay of reversible contraception, they do carry the risk of complications, including septic abortion, abscess formation, ectopic pregnancy, bleeding, and uterine perforation.¹ Although perforation is a relatively rare complication, occurring in 0.3 to 2.6 per 1,000 insertions for levonorgestrel-releasing intrauterine systems and 0.3 to 2.2 per 1,000 insertions for copper IUDs, it can lead to serious complications, including IUD migration to various sites.² Most patients with uterine perforation and IUD migration present with abdominal pain and bleeding; however, 30% of patients are asymptomatic.³

This article presents the case of a young woman who was diagnosed with IUD migration into the abdominal cavity. I discuss the management of this uncommon complication, and stress the importance of adequate education for both patients and health care providers regarding proper surveillance.
 

Case

A 33-year-old woman (gravida 4, para 4, live 4) presented to our ED for evaluation of rectal bleeding that she had experienced intermittently over the past 2 years. She reported that the first occurrence had been 2 years ago, starting a few weeks after she had a cesarean delivery. The patient described the initial episode as bright red blood mixed with stool. She stated that subsequent episodes had been intermittent, felt as if she were “passing rocks” through her abdomen and rectum, and were accompanied by streaks of blood covering her stool. The day before the patient presented to the ED, she had experienced a second episode of a large bowel movement mixed with blood and accompanied by weakness, which prompted her to seek treatment.

A review of the patient’s symptoms revealed abdominal pain and weakness. She denied any bleeding disorders, fever, chills, sick contacts, anal trauma, presyncope, syncope, nausea, vomiting, diarrhea, or constipation. She further denied any prescription-medication use, illicit drug use, or smoking, but admitted to occasional alcohol use. Her last menstrual period had been 3 weeks prior to presentation. She denied any history of cancer or abnormal Pap smears. Her gynecologic history was significant for chlamydia and trichomoniasis, for which she had been treated. The patient’s surgical history was pertinent for umbilical hernia repair with surgical mesh.

On physical examination, the patient was mildly hypotensive (blood pressure, 97/78 mm Hg) but had a normal heart rate. She had mild conjunctival pallor. The abdominal examination exhibited normoactive bowel sounds with diffuse lower abdominal tenderness to deep palpation, but without rebound, guarding, or distension. Rectal examination revealed a small internal hemorrhoid at the 6 o’clock position (no active bleeding) and an external hemorrhoid with some tenderness to palpation; the external hemorrhoid was not thrombosed, had no signs of infection, and was the same color as the surrounding skin.

A fecal occult blood screen was negative, and a serum pregnancy test was also negative. Complete blood count, basic metabolic profile, and urinalysis were all unremarkable and within normal ranges. Abdominal X-ray revealed a nonobstructive stool pattern and a foreign body, likely in the abdominal cavity, which appeared to be an IUD (Figure 1). Computed tomography (CT) scans of the abdomen and pelvis without contrast were performed to accurately locate the foreign body and to assess for any complications. The CT scans revealed an IUD outside of the uterus, between loops of the transverse colon within the left midabdomen (Figure 2). There were no signs of infection, fluid, or free air. There were also findings of colonic diverticula and narrowed lumen, which were suggestive of diverticulosis.

The patient stated that the IUD had been placed several months after the vaginal birth of her third child. She continued to have normal menstrual periods with the IUD in place. Seven years later, she became pregnant with her fourth child, who was delivered via cesarean, secondary to fetal malpositioning. The IUD was not removed during the cesarean delivery.

Based on the CT scan findings, gynecology services was consulted, and the gynecologist recommended immediate follow-up in a gynecology clinic. The patient was discharged on a bowel regimen. She was assessed in a gynecology clinic 4 days later, where she was found to have a mobile retroverted uterus without tenderness or signs of infection. She underwent exploratory laparoscopy, during which the IUD was removed from the omentum in the left upper abdomen without complications.
 

Discussion

The IUD has had great acceptance among women since the 1960s. According to the World Health Organization, approximately 14.3% of women used an IUD in 2009.⁴ Although complications are rare, the most serious are perforation of the uterus and migration of the IUD into adjacent organs.¹

Risk factors of uterine perforation include clinician inexperience in IUD placement, an immobile uterus, a retroverted uterus, and the presence of a myometrial defect.⁴ Heinemann et al² also suggested that breastfeeding and IUD placement soon after a delivery (≤36 weeks) are independent risk factors, and the presence of both factors has an additive increase in risk of perforation.

Primary rupture of the uterus has been reported at the time of IUD insertion, but secondary or delayed rupture is more common and seems to be due to the spasms of the uterus.⁵ Although 85% of perforations do not affect other organs, the remaining 15% lead to complications in the adjacent visceral organs.⁶ The most frequent sites of migration are to the omentum (26.7%), pouch of Douglas (21.5%), large bowel (10.4%), myometrium (7.4%), broad ligament (6.7%), abdominal cavity (5.2%), adhesion to ileal loop serosa (4.4%) or large bowel serosa (3.7%), and mesentery (3%).⁷ Rare sites are to the appendix, abdominal wall, ovary, and bladder.⁷

Intrauterine device migration should be suspected in patients who become pregnant after IUD placement (as was the case for our patient), when the “threads” or string cannot be located while attempting to remove an IUD, or when a patient has an “expulsed” IUD without observation of the device thereafter. Even though expulsion of the device happens in approximately 8 per 1,000 insertions, uterine perforation is also a possibility in the case of a “lost” IUD.⁸ When a lost IUD is suspected, a pelvic examination should be performed to assess for threads or string location. If unsuccessful, ultrasound or plain abdominal radiographic imaging may be used to locate the IUD.  Once IUD migration has been confirmed, cross-sectional imaging such as CT scans or magnetic resonance imaging (MRI) is suggested to rule out adjacent organ involvement before considering surgical removal.⁴ If colonic involvement is suspected, colonoscopy can be used to confirm the diagnosis before operative removal.⁴

Although management of a migrated IUD in an asymptomatic patient is controversial, there appears to be a consensus that all extrauterine devices should be removed unless the patient’s surgical risk is excessive.^1,5,9 Retrieval of an IUD can be performed by laparotomy or laparoscopy.^10,11

To avoid these complications and interventions, IUDs should be inserted by an appropriately trained professional, after proper patient selection. These devices should be monitored by periodic examinations, either by medical professionals or by well-informed patients. This can be done by either checking for the threads or string in the cervical opening or by ultrasound imaging to confirm the location of the IUD.
 

Conclusion

Although many patients with uterine perforation and IUD migration present with symptoms, approximately 30% are asymptomatic.³ If a patient has a lost IUD and the threads or string is not visible during pelvic examination, appropriate work-up, including transvaginal or transabdominal ultrasound or radiographs, should be obtained to confirm the position of the IUD. If IUD migration is suspected, cross-sectional imaging, such as CT scans or MRI, is recommended to rule out adjacent organ involvement before considering surgical removal.⁴

Even though only 15% of migrated IUDs lead to complications in the adjacent visceral organs,⁶ surgical removal of the IUD is advised regardless of the presence of symptoms or identified complications. Importantly, to prevent the delayed diagnosis and morbidity of IUD migration, patients with IUDs should be educated about the possibility of migration and the importance of regular self-examination for missing threads or string.

Although intrauterine devices (IUDs) are a mainstay of reversible contraception, they do carry the risk of complications, including septic abortion, abscess formation, ectopic pregnancy, bleeding, and uterine perforation.¹ Although perforation is a relatively rare complication, occurring in 0.3 to 2.6 per 1,000 insertions for levonorgestrel-releasing intrauterine systems and 0.3 to 2.2 per 1,000 insertions for copper IUDs, it can lead to serious complications, including IUD migration to various sites.² Most patients with uterine perforation and IUD migration present with abdominal pain and bleeding; however, 30% of patients are asymptomatic.³

This article presents the case of a young woman who was diagnosed with IUD migration into the abdominal cavity. I discuss the management of this uncommon complication, and stress the importance of adequate education for both patients and health care providers regarding proper surveillance.
 

Case

A 33-year-old woman (gravida 4, para 4, live 4) presented to our ED for evaluation of rectal bleeding that she had experienced intermittently over the past 2 years. She reported that the first occurrence had been 2 years ago, starting a few weeks after she had a cesarean delivery. The patient described the initial episode as bright red blood mixed with stool. She stated that subsequent episodes had been intermittent, felt as if she were “passing rocks” through her abdomen and rectum, and were accompanied by streaks of blood covering her stool. The day before the patient presented to the ED, she had experienced a second episode of a large bowel movement mixed with blood and accompanied by weakness, which prompted her to seek treatment.

A review of the patient’s symptoms revealed abdominal pain and weakness. She denied any bleeding disorders, fever, chills, sick contacts, anal trauma, presyncope, syncope, nausea, vomiting, diarrhea, or constipation. She further denied any prescription-medication use, illicit drug use, or smoking, but admitted to occasional alcohol use. Her last menstrual period had been 3 weeks prior to presentation. She denied any history of cancer or abnormal Pap smears. Her gynecologic history was significant for chlamydia and trichomoniasis, for which she had been treated. The patient’s surgical history was pertinent for umbilical hernia repair with surgical mesh.

On physical examination, the patient was mildly hypotensive (blood pressure, 97/78 mm Hg) but had a normal heart rate. She had mild conjunctival pallor. The abdominal examination exhibited normoactive bowel sounds with diffuse lower abdominal tenderness to deep palpation, but without rebound, guarding, or distension. Rectal examination revealed a small internal hemorrhoid at the 6 o’clock position (no active bleeding) and an external hemorrhoid with some tenderness to palpation; the external hemorrhoid was not thrombosed, had no signs of infection, and was the same color as the surrounding skin.

A fecal occult blood screen was negative, and a serum pregnancy test was also negative. Complete blood count, basic metabolic profile, and urinalysis were all unremarkable and within normal ranges. Abdominal X-ray revealed a nonobstructive stool pattern and a foreign body, likely in the abdominal cavity, which appeared to be an IUD (Figure 1). Computed tomography (CT) scans of the abdomen and pelvis without contrast were performed to accurately locate the foreign body and to assess for any complications. The CT scans revealed an IUD outside of the uterus, between loops of the transverse colon within the left midabdomen (Figure 2). There were no signs of infection, fluid, or free air. There were also findings of colonic diverticula and narrowed lumen, which were suggestive of diverticulosis.

The patient stated that the IUD had been placed several months after the vaginal birth of her third child. She continued to have normal menstrual periods with the IUD in place. Seven years later, she became pregnant with her fourth child, who was delivered via cesarean, secondary to fetal malpositioning. The IUD was not removed during the cesarean delivery.

Based on the CT scan findings, gynecology services was consulted, and the gynecologist recommended immediate follow-up in a gynecology clinic. The patient was discharged on a bowel regimen. She was assessed in a gynecology clinic 4 days later, where she was found to have a mobile retroverted uterus without tenderness or signs of infection. She underwent exploratory laparoscopy, during which the IUD was removed from the omentum in the left upper abdomen without complications.
 

Discussion

The IUD has had great acceptance among women since the 1960s. According to the World Health Organization, approximately 14.3% of women used an IUD in 2009.⁴ Although complications are rare, the most serious are perforation of the uterus and migration of the IUD into adjacent organs.¹

Risk factors of uterine perforation include clinician inexperience in IUD placement, an immobile uterus, a retroverted uterus, and the presence of a myometrial defect.⁴ Heinemann et al² also suggested that breastfeeding and IUD placement soon after a delivery (≤36 weeks) are independent risk factors, and the presence of both factors has an additive increase in risk of perforation.

Primary rupture of the uterus has been reported at the time of IUD insertion, but secondary or delayed rupture is more common and seems to be due to the spasms of the uterus.⁵ Although 85% of perforations do not affect other organs, the remaining 15% lead to complications in the adjacent visceral organs.⁶ The most frequent sites of migration are to the omentum (26.7%), pouch of Douglas (21.5%), large bowel (10.4%), myometrium (7.4%), broad ligament (6.7%), abdominal cavity (5.2%), adhesion to ileal loop serosa (4.4%) or large bowel serosa (3.7%), and mesentery (3%).⁷ Rare sites are to the appendix, abdominal wall, ovary, and bladder.⁷

Intrauterine device migration should be suspected in patients who become pregnant after IUD placement (as was the case for our patient), when the “threads” or string cannot be located while attempting to remove an IUD, or when a patient has an “expulsed” IUD without observation of the device thereafter. Even though expulsion of the device happens in approximately 8 per 1,000 insertions, uterine perforation is also a possibility in the case of a “lost” IUD.⁸ When a lost IUD is suspected, a pelvic examination should be performed to assess for threads or string location. If unsuccessful, ultrasound or plain abdominal radiographic imaging may be used to locate the IUD.  Once IUD migration has been confirmed, cross-sectional imaging such as CT scans or magnetic resonance imaging (MRI) is suggested to rule out adjacent organ involvement before considering surgical removal.⁴ If colonic involvement is suspected, colonoscopy can be used to confirm the diagnosis before operative removal.⁴

Although management of a migrated IUD in an asymptomatic patient is controversial, there appears to be a consensus that all extrauterine devices should be removed unless the patient’s surgical risk is excessive.^1,5,9 Retrieval of an IUD can be performed by laparotomy or laparoscopy.^10,11

To avoid these complications and interventions, IUDs should be inserted by an appropriately trained professional, after proper patient selection. These devices should be monitored by periodic examinations, either by medical professionals or by well-informed patients. This can be done by either checking for the threads or string in the cervical opening or by ultrasound imaging to confirm the location of the IUD.
 

Conclusion

Although many patients with uterine perforation and IUD migration present with symptoms, approximately 30% are asymptomatic.³ If a patient has a lost IUD and the threads or string is not visible during pelvic examination, appropriate work-up, including transvaginal or transabdominal ultrasound or radiographs, should be obtained to confirm the position of the IUD. If IUD migration is suspected, cross-sectional imaging, such as CT scans or MRI, is recommended to rule out adjacent organ involvement before considering surgical removal.⁴

Even though only 15% of migrated IUDs lead to complications in the adjacent visceral organs,⁶ surgical removal of the IUD is advised regardless of the presence of symptoms or identified complications. Importantly, to prevent the delayed diagnosis and morbidity of IUD migration, patients with IUDs should be educated about the possibility of migration and the importance of regular self-examination for missing threads or string.

Although intrauterine devices (IUDs) are a mainstay of reversible contraception, they do carry the risk of complications, including septic abortion, abscess formation, ectopic pregnancy, bleeding, and uterine perforation.¹ Although perforation is a relatively rare complication, occurring in 0.3 to 2.6 per 1,000 insertions for levonorgestrel-releasing intrauterine systems and 0.3 to 2.2 per 1,000 insertions for copper IUDs, it can lead to serious complications, including IUD migration to various sites.² Most patients with uterine perforation and IUD migration present with abdominal pain and bleeding; however, 30% of patients are asymptomatic.³

This article presents the case of a young woman who was diagnosed with IUD migration into the abdominal cavity. I discuss the management of this uncommon complication, and stress the importance of adequate education for both patients and health care providers regarding proper surveillance.
 

Case

A 33-year-old woman (gravida 4, para 4, live 4) presented to our ED for evaluation of rectal bleeding that she had experienced intermittently over the past 2 years. She reported that the first occurrence had been 2 years ago, starting a few weeks after she had a cesarean delivery. The patient described the initial episode as bright red blood mixed with stool. She stated that subsequent episodes had been intermittent, felt as if she were “passing rocks” through her abdomen and rectum, and were accompanied by streaks of blood covering her stool. The day before the patient presented to the ED, she had experienced a second episode of a large bowel movement mixed with blood and accompanied by weakness, which prompted her to seek treatment.

A review of the patient’s symptoms revealed abdominal pain and weakness. She denied any bleeding disorders, fever, chills, sick contacts, anal trauma, presyncope, syncope, nausea, vomiting, diarrhea, or constipation. She further denied any prescription-medication use, illicit drug use, or smoking, but admitted to occasional alcohol use. Her last menstrual period had been 3 weeks prior to presentation. She denied any history of cancer or abnormal Pap smears. Her gynecologic history was significant for chlamydia and trichomoniasis, for which she had been treated. The patient’s surgical history was pertinent for umbilical hernia repair with surgical mesh.

On physical examination, the patient was mildly hypotensive (blood pressure, 97/78 mm Hg) but had a normal heart rate. She had mild conjunctival pallor. The abdominal examination exhibited normoactive bowel sounds with diffuse lower abdominal tenderness to deep palpation, but without rebound, guarding, or distension. Rectal examination revealed a small internal hemorrhoid at the 6 o’clock position (no active bleeding) and an external hemorrhoid with some tenderness to palpation; the external hemorrhoid was not thrombosed, had no signs of infection, and was the same color as the surrounding skin.

A fecal occult blood screen was negative, and a serum pregnancy test was also negative. Complete blood count, basic metabolic profile, and urinalysis were all unremarkable and within normal ranges. Abdominal X-ray revealed a nonobstructive stool pattern and a foreign body, likely in the abdominal cavity, which appeared to be an IUD (Figure 1). Computed tomography (CT) scans of the abdomen and pelvis without contrast were performed to accurately locate the foreign body and to assess for any complications. The CT scans revealed an IUD outside of the uterus, between loops of the transverse colon within the left midabdomen (Figure 2). There were no signs of infection, fluid, or free air. There were also findings of colonic diverticula and narrowed lumen, which were suggestive of diverticulosis.

The patient stated that the IUD had been placed several months after the vaginal birth of her third child. She continued to have normal menstrual periods with the IUD in place. Seven years later, she became pregnant with her fourth child, who was delivered via cesarean, secondary to fetal malpositioning. The IUD was not removed during the cesarean delivery.

Based on the CT scan findings, gynecology services was consulted, and the gynecologist recommended immediate follow-up in a gynecology clinic. The patient was discharged on a bowel regimen. She was assessed in a gynecology clinic 4 days later, where she was found to have a mobile retroverted uterus without tenderness or signs of infection. She underwent exploratory laparoscopy, during which the IUD was removed from the omentum in the left upper abdomen without complications.
 

Discussion

The IUD has had great acceptance among women since the 1960s. According to the World Health Organization, approximately 14.3% of women used an IUD in 2009.⁴ Although complications are rare, the most serious are perforation of the uterus and migration of the IUD into adjacent organs.¹

Risk factors of uterine perforation include clinician inexperience in IUD placement, an immobile uterus, a retroverted uterus, and the presence of a myometrial defect.⁴ Heinemann et al² also suggested that breastfeeding and IUD placement soon after a delivery (≤36 weeks) are independent risk factors, and the presence of both factors has an additive increase in risk of perforation.

Primary rupture of the uterus has been reported at the time of IUD insertion, but secondary or delayed rupture is more common and seems to be due to the spasms of the uterus.⁵ Although 85% of perforations do not affect other organs, the remaining 15% lead to complications in the adjacent visceral organs.⁶ The most frequent sites of migration are to the omentum (26.7%), pouch of Douglas (21.5%), large bowel (10.4%), myometrium (7.4%), broad ligament (6.7%), abdominal cavity (5.2%), adhesion to ileal loop serosa (4.4%) or large bowel serosa (3.7%), and mesentery (3%).⁷ Rare sites are to the appendix, abdominal wall, ovary, and bladder.⁷

Intrauterine device migration should be suspected in patients who become pregnant after IUD placement (as was the case for our patient), when the “threads” or string cannot be located while attempting to remove an IUD, or when a patient has an “expulsed” IUD without observation of the device thereafter. Even though expulsion of the device happens in approximately 8 per 1,000 insertions, uterine perforation is also a possibility in the case of a “lost” IUD.⁸ When a lost IUD is suspected, a pelvic examination should be performed to assess for threads or string location. If unsuccessful, ultrasound or plain abdominal radiographic imaging may be used to locate the IUD.  Once IUD migration has been confirmed, cross-sectional imaging such as CT scans or magnetic resonance imaging (MRI) is suggested to rule out adjacent organ involvement before considering surgical removal.⁴ If colonic involvement is suspected, colonoscopy can be used to confirm the diagnosis before operative removal.⁴

Although management of a migrated IUD in an asymptomatic patient is controversial, there appears to be a consensus that all extrauterine devices should be removed unless the patient’s surgical risk is excessive.^1,5,9 Retrieval of an IUD can be performed by laparotomy or laparoscopy.^10,11

To avoid these complications and interventions, IUDs should be inserted by an appropriately trained professional, after proper patient selection. These devices should be monitored by periodic examinations, either by medical professionals or by well-informed patients. This can be done by either checking for the threads or string in the cervical opening or by ultrasound imaging to confirm the location of the IUD.
 

Conclusion

Although many patients with uterine perforation and IUD migration present with symptoms, approximately 30% are asymptomatic.³ If a patient has a lost IUD and the threads or string is not visible during pelvic examination, appropriate work-up, including transvaginal or transabdominal ultrasound or radiographs, should be obtained to confirm the position of the IUD. If IUD migration is suspected, cross-sectional imaging, such as CT scans or MRI, is recommended to rule out adjacent organ involvement before considering surgical removal.⁴

Even though only 15% of migrated IUDs lead to complications in the adjacent visceral organs,⁶ surgical removal of the IUD is advised regardless of the presence of symptoms or identified complications. Importantly, to prevent the delayed diagnosis and morbidity of IUD migration, patients with IUDs should be educated about the possibility of migration and the importance of regular self-examination for missing threads or string.

Dengue fever is the most commonly transmitted arboviral disease in the world, affecting an estimated 2.5 billion people who live in areas endemic to the virus. This exposure yields an annual incidence of 100 million cases of dengue, which translates into 250,000 cases of hemorrhagic fever. With an expanding geographic distribution and increasing number of epidemics, the World Health Organization (WHO) has classified dengue as a major public health concern.¹ Enhanced globalization and changing climate patterns have resulted in a dramatic increase in the incidence of dengue in both North and Central America. Aggregate North and Central American data from 2010 to the present revealed over 1.7 million cases of dengue, nearly 80,000 of which were severe, and 747 deaths.² Based on these statistics, dengue fever should be considered in the differential diagnosis of febrile ED patients in the developed world who had a history of recent travel. We present two cases that highlight the complexity of diagnosis and novel complications associated with dengue fever.

Case Reports

Case 1

A 24-year-old man presented to the ED with a 4-day history of intermittent fever of up to 102.02°F, which was accompanied by chills, myalgia, and rigors. The patient stated that he had visited Vietnam, Thailand, Indonesia, and Malaysia 8 days prior to presentation, and had experienced mosquito bites daily throughout his travels. He further noted that his symptoms had improved on day 3 of his illness, but acutely worsened on day 4, which prompted him to visit the ED. The patient’s primary complaint was a severe retro-orbital headache, fever, and one episode of epistaxis.

On physical examination, the patient had conjunctivitis and hepatosplenomegaly, but otherwise appeared well. His laboratory evaluation was significant for leukopenia (white blood cell [WBC] count, 2.40 x 10⁹/L), thrombocytopenia (platelet count, 123 x 10⁹/L), and a positive mononuclear spot test. Both dengue immunoglobulin G (IgG) and immunoglobulin M (IgM) tests sent from the ED were negative. Based on the patient’s thrombocytopenia and epistaxis, as well as concerns that the patient was entering into the critical phase of dengue fever, he was admitted to the inpatient hospital for observation.

The patient’s course improved during his stay with symptomatic treatment and blood-count monitoring, and he was discharged home on hospital day 3. He followed up at our hospital travel clinic the day after discharge; a repeat dengue IgM test taken during this visit came back positive.

Case 2

A 51-year-old man presented to the ED with a 3-day history of intermittent fever and diffuse myalgia. He reported chills, night sweats, and the feeling of abdominal fullness. He denied nausea, vomiting, or changes in the character of his stool. He had no known sick contacts, but reported he had traveled from the Philippines 3 days prior to presentation and that his symptoms had developed en route to the United States. The patient also denied any known tick, mosquito, or animal exposures. He said he had treated his symptoms with acetaminophen and nonsteroidal anti-inflammatory drugs. Prior to his arrival at the ED, he had twice presented to a walk-in clinic earlier that day. Repeated laboratory testing at the ED showed a decrease in WBC count from 42.0 x 10⁹/L to 31.0 x 10⁹/L, as well as a declining platelet count from 123 x 10⁹/L to 87 x 10⁹/L. On physical examination, the patient was ill-appearing, diaphoretic, and had a temperature of 100.6°F. His vital signs were otherwise within normal limits.

With the exception of a mild diffuse petechial rash on the patient’s thighs bilaterally, the physical examination was unrevealing. A tourniquet test (TT) to assess capillary fragility was performed at bedside, and yielded a positive result (Figure 1). Work-up further demonstrated a declining WBC of 2.70 x 10⁹/L and declining platelet count of 65 x 10⁹/L.

A polymerase chain reaction (PCR) test confirmed a diagnosis of dengue, with a positive dengue type-4 (DEN-4) serotype detection. Supportive care was initiated, and the patient was admitted to the inpatient hospital for continued treatment. He was discharged home on hospital day 5; however, he returned to the ED later that day with increasing headache and left flank pain. Work-up included axial and coronal computed tomography scans of the abdomen and pelvis, which revealed hematuria and a left upper pole renal infarction surrounded by mild perinephric fat stranding (Figure 2a and 2b) with maintenance of left renal artery/vein patency.

The patient was admitted to an inpatient floor, where symptomatic management was employed. He underwent unrevealing bubble echocardiography and lower extremity Doppler ultrasound imaging, and anticoagulation therapy was initiated per a consultation with hematology services. The patient was discharged home in improved, stable condition on hospital day 8.

Discussion

Dengue virus is a single-stranded, nonsegmented RNA virus in the Flaviviridae family. Four major subtypes exist: DEN-1, DEN-2, DEN-3, and DEN-4. Lifelong serotype-specific immunity is conferred following infection. The virus is transmitted by the female Aedes aegypti mosquito, which is found worldwide but has a predilection for tropical and subtropical regions. The Aedes aegypti mosquito remains an effective vector secondary to its diurnal feeding habit and nearly imperceptible bite.^1,3

The viral incubation period for dengue is typically 3 to 7 days⁴; therefore, dengue is highly unlikely in patients whose symptoms begin more than 2 weeks after departure from an endemic area. Replication primarily occurs in the regional lymph nodes and disseminates through the lymphatic system and bloodstream.¹

The 1997 WHO guidelines previously classified dengue into three categories: undifferentiated fever, dengue fever, and dengue hemorrhagic fever (which was further classified by four severity grades, with grades III and IV defined as dengue shock syndrome). However, changes in epidemiology of the disease and reports of difficulty applying the criteria in the clinical setting led to reclassification of dengue on a continuum from dengue to severe dengue in the WHO’s updated 2009 guidelines.⁴

Signs and Symptoms

The ramifications of dengue infection can range from asymptomatic (typically in young, immunocompetent patients) to lethal. Key symptoms of dengue fever include nausea, vomiting, fever, respiratory symptoms, morbilliform or maculopapular rash, and headache or retro-orbital pain. In addition, arthralgia (hence the colloquial name for dengue of “breakbone fever”), myalgia, and conjunctivitis may exist.^3,4 Fever usually lasts 5 to 7 days and can be biphasic, with a return of symptoms after the initial resolution as seen in case report 1.⁴  Severe dengue is characterized by capillary leakage, hemorrhage, or end-organ damage.^3-5 The most common bleeding sites are the skin, nose, and gums.

Diagnosis

Bedside evaluation for dengue can be performed with the TT—one of the WHO’s case definitions for dengue.⁶ This is accomplished by placing a manual blood pressure (BP) cuff on the arm and inflating it to halfway between systolic and diastolic BP for 5 minutes. The test is positive for dengue if more than 10 petechiae appear per 1-inch (2.5-cm) square below the antecubital fossa.⁷ Of note, the test has poor sensitivity (51.6%, 95% confidence interval [CI], 33-69), but good specificity (82.4%, 95% CI, 76-87).^7,8 A positive TT combined with leukopenia increases the sensitivity to 93.9%, [95% CI, 89-96].⁷ While not specific to dengue infection, in the right clinical scenario, the TT is a simple bedside test to help confirm the diagnosis and is extremely useful in resource-limited settings. 

During the initial days of illness, the virus may be detected by PCR, as viremia and fever usually correlate. Once defervescence occurs, IgM and then IgG antibodies become detectable. When using these antibody tests to evaluate for dengue, clinicians should be aware of cross-reactivity with other flavivirus infections, such as yellow fever or Japanese encephalitis (including immunological cross-reactivity).¹ New diagnostic modalities include enzyme immunoassays that can detect dengue viral RNA within 24 to 48 hours, and viral antigen-detection kits, which can yield results in less than 1 hour.⁴

Aside from advanced laboratory testing, worsening thrombocytopenia in light of a rising hematocrit can be highly suggestive of dengue. Leukopenia with lymphopenia and mild elevation of hepatic enzymes (typically 2 to 5 times the upper limits of the normal reference range) are also often seen in active infections.¹ The occurrence of these signs in conjunction with a rapid reduction in the platelets often signals transition to the critical phase of plasma leakage.^1,4

Treatment

Treatment of dengue consists of supportive care and transfusion when necessary. The WHO recommends strict observation of patients with suspected dengue who have warning signs of severe disease (eg, abdominal pain, persistent vomiting, mucosal bleeding, lethargy, hepatomegaly, rapid increase in hematocrit with concomitant drop in platelet count). Inpatient treatment centers on judicious fluid management, trending blood count parameters, and monitoring for signs of plasma leakage and hemorrhage. Fluid resuscitation is titrated to optimize central and peripheral circulation and end-organ perfusion. Blood-product administration should be reserved for suspected or severe bleeding.⁴

While dengue fever was the final diagnosis in both of our case presentations, these cases also highlight key diagnostic and treatment dilemmas associated with dengue. The patient in the first case report demonstrated the characteristic biphasic fever seen with dengue—resolution of symptoms on day 3, but then return of fever and symptoms on day 4. Often the dengue-specific antibodies are not formed until after the resolution of fever. This patient represents a classic example of dengue as the serologic studies sent on day 4 of the patient’s illness were negative but then turned positive on day 7, illustrating the need for high clinical suspicion and underscoring the importance of initiating treatment despite laboratory confirmation.

Further, regarding the patient in the second case, though proteinuria, hematuria, acute renal failure, and glomerulonephritis are previously described renal complications of dengue,⁹ a thorough literature search yielded no prior published accounts of renal infarction. Given the patient’s previous healthy status and the lack of other hypothesis as to the mechanism of injury, we suspect this patient’s renal infarction was due to the transient hypercoagulability characteristic of dengue and responsible for other clinical manifestations of the disease.

Conclusion

In addition to more prevalent illnesses such as malaria, acute traveler’s diarrhea, and respiratory tract infections, dengue fever should be included in the differential diagnosis when evaluating a febrile patient who has a history of recent travel to countries where dengue is endemic. A high clinical suspicion, combined with a thorough history and physical examination, is essential to making the diagnosis.

Both of our case reports demonstrate some of the diagnostic limitations in the acute setting, and the breadth of clinical complications that can occur in this complex disease. With the increasing prevalence of dengue fever in North and Central America, it is likely that patients with the disease will present to EDs in the United States. Early diagnosis and awareness of potential complications can lead to timely initiation of life-saving supportive care.

Dengue fever is the most commonly transmitted arboviral disease in the world, affecting an estimated 2.5 billion people who live in areas endemic to the virus. This exposure yields an annual incidence of 100 million cases of dengue, which translates into 250,000 cases of hemorrhagic fever. With an expanding geographic distribution and increasing number of epidemics, the World Health Organization (WHO) has classified dengue as a major public health concern.¹ Enhanced globalization and changing climate patterns have resulted in a dramatic increase in the incidence of dengue in both North and Central America. Aggregate North and Central American data from 2010 to the present revealed over 1.7 million cases of dengue, nearly 80,000 of which were severe, and 747 deaths.² Based on these statistics, dengue fever should be considered in the differential diagnosis of febrile ED patients in the developed world who had a history of recent travel. We present two cases that highlight the complexity of diagnosis and novel complications associated with dengue fever.

Case Reports

Case 1

A 24-year-old man presented to the ED with a 4-day history of intermittent fever of up to 102.02°F, which was accompanied by chills, myalgia, and rigors. The patient stated that he had visited Vietnam, Thailand, Indonesia, and Malaysia 8 days prior to presentation, and had experienced mosquito bites daily throughout his travels. He further noted that his symptoms had improved on day 3 of his illness, but acutely worsened on day 4, which prompted him to visit the ED. The patient’s primary complaint was a severe retro-orbital headache, fever, and one episode of epistaxis.

On physical examination, the patient had conjunctivitis and hepatosplenomegaly, but otherwise appeared well. His laboratory evaluation was significant for leukopenia (white blood cell [WBC] count, 2.40 x 10⁹/L), thrombocytopenia (platelet count, 123 x 10⁹/L), and a positive mononuclear spot test. Both dengue immunoglobulin G (IgG) and immunoglobulin M (IgM) tests sent from the ED were negative. Based on the patient’s thrombocytopenia and epistaxis, as well as concerns that the patient was entering into the critical phase of dengue fever, he was admitted to the inpatient hospital for observation.

The patient’s course improved during his stay with symptomatic treatment and blood-count monitoring, and he was discharged home on hospital day 3. He followed up at our hospital travel clinic the day after discharge; a repeat dengue IgM test taken during this visit came back positive.

Case 2

A 51-year-old man presented to the ED with a 3-day history of intermittent fever and diffuse myalgia. He reported chills, night sweats, and the feeling of abdominal fullness. He denied nausea, vomiting, or changes in the character of his stool. He had no known sick contacts, but reported he had traveled from the Philippines 3 days prior to presentation and that his symptoms had developed en route to the United States. The patient also denied any known tick, mosquito, or animal exposures. He said he had treated his symptoms with acetaminophen and nonsteroidal anti-inflammatory drugs. Prior to his arrival at the ED, he had twice presented to a walk-in clinic earlier that day. Repeated laboratory testing at the ED showed a decrease in WBC count from 42.0 x 10⁹/L to 31.0 x 10⁹/L, as well as a declining platelet count from 123 x 10⁹/L to 87 x 10⁹/L. On physical examination, the patient was ill-appearing, diaphoretic, and had a temperature of 100.6°F. His vital signs were otherwise within normal limits.

With the exception of a mild diffuse petechial rash on the patient’s thighs bilaterally, the physical examination was unrevealing. A tourniquet test (TT) to assess capillary fragility was performed at bedside, and yielded a positive result (Figure 1). Work-up further demonstrated a declining WBC of 2.70 x 10⁹/L and declining platelet count of 65 x 10⁹/L.

A polymerase chain reaction (PCR) test confirmed a diagnosis of dengue, with a positive dengue type-4 (DEN-4) serotype detection. Supportive care was initiated, and the patient was admitted to the inpatient hospital for continued treatment. He was discharged home on hospital day 5; however, he returned to the ED later that day with increasing headache and left flank pain. Work-up included axial and coronal computed tomography scans of the abdomen and pelvis, which revealed hematuria and a left upper pole renal infarction surrounded by mild perinephric fat stranding (Figure 2a and 2b) with maintenance of left renal artery/vein patency.

The patient was admitted to an inpatient floor, where symptomatic management was employed. He underwent unrevealing bubble echocardiography and lower extremity Doppler ultrasound imaging, and anticoagulation therapy was initiated per a consultation with hematology services. The patient was discharged home in improved, stable condition on hospital day 8.

Discussion

Dengue virus is a single-stranded, nonsegmented RNA virus in the Flaviviridae family. Four major subtypes exist: DEN-1, DEN-2, DEN-3, and DEN-4. Lifelong serotype-specific immunity is conferred following infection. The virus is transmitted by the female Aedes aegypti mosquito, which is found worldwide but has a predilection for tropical and subtropical regions. The Aedes aegypti mosquito remains an effective vector secondary to its diurnal feeding habit and nearly imperceptible bite.^1,3

The viral incubation period for dengue is typically 3 to 7 days⁴; therefore, dengue is highly unlikely in patients whose symptoms begin more than 2 weeks after departure from an endemic area. Replication primarily occurs in the regional lymph nodes and disseminates through the lymphatic system and bloodstream.¹

The 1997 WHO guidelines previously classified dengue into three categories: undifferentiated fever, dengue fever, and dengue hemorrhagic fever (which was further classified by four severity grades, with grades III and IV defined as dengue shock syndrome). However, changes in epidemiology of the disease and reports of difficulty applying the criteria in the clinical setting led to reclassification of dengue on a continuum from dengue to severe dengue in the WHO’s updated 2009 guidelines.⁴

Signs and Symptoms

The ramifications of dengue infection can range from asymptomatic (typically in young, immunocompetent patients) to lethal. Key symptoms of dengue fever include nausea, vomiting, fever, respiratory symptoms, morbilliform or maculopapular rash, and headache or retro-orbital pain. In addition, arthralgia (hence the colloquial name for dengue of “breakbone fever”), myalgia, and conjunctivitis may exist.^3,4 Fever usually lasts 5 to 7 days and can be biphasic, with a return of symptoms after the initial resolution as seen in case report 1.⁴  Severe dengue is characterized by capillary leakage, hemorrhage, or end-organ damage.^3-5 The most common bleeding sites are the skin, nose, and gums.

Diagnosis

Bedside evaluation for dengue can be performed with the TT—one of the WHO’s case definitions for dengue.⁶ This is accomplished by placing a manual blood pressure (BP) cuff on the arm and inflating it to halfway between systolic and diastolic BP for 5 minutes. The test is positive for dengue if more than 10 petechiae appear per 1-inch (2.5-cm) square below the antecubital fossa.⁷ Of note, the test has poor sensitivity (51.6%, 95% confidence interval [CI], 33-69), but good specificity (82.4%, 95% CI, 76-87).^7,8 A positive TT combined with leukopenia increases the sensitivity to 93.9%, [95% CI, 89-96].⁷ While not specific to dengue infection, in the right clinical scenario, the TT is a simple bedside test to help confirm the diagnosis and is extremely useful in resource-limited settings. 

During the initial days of illness, the virus may be detected by PCR, as viremia and fever usually correlate. Once defervescence occurs, IgM and then IgG antibodies become detectable. When using these antibody tests to evaluate for dengue, clinicians should be aware of cross-reactivity with other flavivirus infections, such as yellow fever or Japanese encephalitis (including immunological cross-reactivity).¹ New diagnostic modalities include enzyme immunoassays that can detect dengue viral RNA within 24 to 48 hours, and viral antigen-detection kits, which can yield results in less than 1 hour.⁴

Aside from advanced laboratory testing, worsening thrombocytopenia in light of a rising hematocrit can be highly suggestive of dengue. Leukopenia with lymphopenia and mild elevation of hepatic enzymes (typically 2 to 5 times the upper limits of the normal reference range) are also often seen in active infections.¹ The occurrence of these signs in conjunction with a rapid reduction in the platelets often signals transition to the critical phase of plasma leakage.^1,4

Treatment

Treatment of dengue consists of supportive care and transfusion when necessary. The WHO recommends strict observation of patients with suspected dengue who have warning signs of severe disease (eg, abdominal pain, persistent vomiting, mucosal bleeding, lethargy, hepatomegaly, rapid increase in hematocrit with concomitant drop in platelet count). Inpatient treatment centers on judicious fluid management, trending blood count parameters, and monitoring for signs of plasma leakage and hemorrhage. Fluid resuscitation is titrated to optimize central and peripheral circulation and end-organ perfusion. Blood-product administration should be reserved for suspected or severe bleeding.⁴

While dengue fever was the final diagnosis in both of our case presentations, these cases also highlight key diagnostic and treatment dilemmas associated with dengue. The patient in the first case report demonstrated the characteristic biphasic fever seen with dengue—resolution of symptoms on day 3, but then return of fever and symptoms on day 4. Often the dengue-specific antibodies are not formed until after the resolution of fever. This patient represents a classic example of dengue as the serologic studies sent on day 4 of the patient’s illness were negative but then turned positive on day 7, illustrating the need for high clinical suspicion and underscoring the importance of initiating treatment despite laboratory confirmation.

Further, regarding the patient in the second case, though proteinuria, hematuria, acute renal failure, and glomerulonephritis are previously described renal complications of dengue,⁹ a thorough literature search yielded no prior published accounts of renal infarction. Given the patient’s previous healthy status and the lack of other hypothesis as to the mechanism of injury, we suspect this patient’s renal infarction was due to the transient hypercoagulability characteristic of dengue and responsible for other clinical manifestations of the disease.

Conclusion

In addition to more prevalent illnesses such as malaria, acute traveler’s diarrhea, and respiratory tract infections, dengue fever should be included in the differential diagnosis when evaluating a febrile patient who has a history of recent travel to countries where dengue is endemic. A high clinical suspicion, combined with a thorough history and physical examination, is essential to making the diagnosis.

Both of our case reports demonstrate some of the diagnostic limitations in the acute setting, and the breadth of clinical complications that can occur in this complex disease. With the increasing prevalence of dengue fever in North and Central America, it is likely that patients with the disease will present to EDs in the United States. Early diagnosis and awareness of potential complications can lead to timely initiation of life-saving supportive care.

Dengue fever is the most commonly transmitted arboviral disease in the world, affecting an estimated 2.5 billion people who live in areas endemic to the virus. This exposure yields an annual incidence of 100 million cases of dengue, which translates into 250,000 cases of hemorrhagic fever. With an expanding geographic distribution and increasing number of epidemics, the World Health Organization (WHO) has classified dengue as a major public health concern.¹ Enhanced globalization and changing climate patterns have resulted in a dramatic increase in the incidence of dengue in both North and Central America. Aggregate North and Central American data from 2010 to the present revealed over 1.7 million cases of dengue, nearly 80,000 of which were severe, and 747 deaths.² Based on these statistics, dengue fever should be considered in the differential diagnosis of febrile ED patients in the developed world who had a history of recent travel. We present two cases that highlight the complexity of diagnosis and novel complications associated with dengue fever.

Case Reports

Case 1

A 24-year-old man presented to the ED with a 4-day history of intermittent fever of up to 102.02°F, which was accompanied by chills, myalgia, and rigors. The patient stated that he had visited Vietnam, Thailand, Indonesia, and Malaysia 8 days prior to presentation, and had experienced mosquito bites daily throughout his travels. He further noted that his symptoms had improved on day 3 of his illness, but acutely worsened on day 4, which prompted him to visit the ED. The patient’s primary complaint was a severe retro-orbital headache, fever, and one episode of epistaxis.

On physical examination, the patient had conjunctivitis and hepatosplenomegaly, but otherwise appeared well. His laboratory evaluation was significant for leukopenia (white blood cell [WBC] count, 2.40 x 10⁹/L), thrombocytopenia (platelet count, 123 x 10⁹/L), and a positive mononuclear spot test. Both dengue immunoglobulin G (IgG) and immunoglobulin M (IgM) tests sent from the ED were negative. Based on the patient’s thrombocytopenia and epistaxis, as well as concerns that the patient was entering into the critical phase of dengue fever, he was admitted to the inpatient hospital for observation.

The patient’s course improved during his stay with symptomatic treatment and blood-count monitoring, and he was discharged home on hospital day 3. He followed up at our hospital travel clinic the day after discharge; a repeat dengue IgM test taken during this visit came back positive.

Case 2

A 51-year-old man presented to the ED with a 3-day history of intermittent fever and diffuse myalgia. He reported chills, night sweats, and the feeling of abdominal fullness. He denied nausea, vomiting, or changes in the character of his stool. He had no known sick contacts, but reported he had traveled from the Philippines 3 days prior to presentation and that his symptoms had developed en route to the United States. The patient also denied any known tick, mosquito, or animal exposures. He said he had treated his symptoms with acetaminophen and nonsteroidal anti-inflammatory drugs. Prior to his arrival at the ED, he had twice presented to a walk-in clinic earlier that day. Repeated laboratory testing at the ED showed a decrease in WBC count from 42.0 x 10⁹/L to 31.0 x 10⁹/L, as well as a declining platelet count from 123 x 10⁹/L to 87 x 10⁹/L. On physical examination, the patient was ill-appearing, diaphoretic, and had a temperature of 100.6°F. His vital signs were otherwise within normal limits.

With the exception of a mild diffuse petechial rash on the patient’s thighs bilaterally, the physical examination was unrevealing. A tourniquet test (TT) to assess capillary fragility was performed at bedside, and yielded a positive result (Figure 1). Work-up further demonstrated a declining WBC of 2.70 x 10⁹/L and declining platelet count of 65 x 10⁹/L.

A polymerase chain reaction (PCR) test confirmed a diagnosis of dengue, with a positive dengue type-4 (DEN-4) serotype detection. Supportive care was initiated, and the patient was admitted to the inpatient hospital for continued treatment. He was discharged home on hospital day 5; however, he returned to the ED later that day with increasing headache and left flank pain. Work-up included axial and coronal computed tomography scans of the abdomen and pelvis, which revealed hematuria and a left upper pole renal infarction surrounded by mild perinephric fat stranding (Figure 2a and 2b) with maintenance of left renal artery/vein patency.

The patient was admitted to an inpatient floor, where symptomatic management was employed. He underwent unrevealing bubble echocardiography and lower extremity Doppler ultrasound imaging, and anticoagulation therapy was initiated per a consultation with hematology services. The patient was discharged home in improved, stable condition on hospital day 8.

Discussion

Dengue virus is a single-stranded, nonsegmented RNA virus in the Flaviviridae family. Four major subtypes exist: DEN-1, DEN-2, DEN-3, and DEN-4. Lifelong serotype-specific immunity is conferred following infection. The virus is transmitted by the female Aedes aegypti mosquito, which is found worldwide but has a predilection for tropical and subtropical regions. The Aedes aegypti mosquito remains an effective vector secondary to its diurnal feeding habit and nearly imperceptible bite.^1,3

The viral incubation period for dengue is typically 3 to 7 days⁴; therefore, dengue is highly unlikely in patients whose symptoms begin more than 2 weeks after departure from an endemic area. Replication primarily occurs in the regional lymph nodes and disseminates through the lymphatic system and bloodstream.¹

The 1997 WHO guidelines previously classified dengue into three categories: undifferentiated fever, dengue fever, and dengue hemorrhagic fever (which was further classified by four severity grades, with grades III and IV defined as dengue shock syndrome). However, changes in epidemiology of the disease and reports of difficulty applying the criteria in the clinical setting led to reclassification of dengue on a continuum from dengue to severe dengue in the WHO’s updated 2009 guidelines.⁴

Signs and Symptoms

The ramifications of dengue infection can range from asymptomatic (typically in young, immunocompetent patients) to lethal. Key symptoms of dengue fever include nausea, vomiting, fever, respiratory symptoms, morbilliform or maculopapular rash, and headache or retro-orbital pain. In addition, arthralgia (hence the colloquial name for dengue of “breakbone fever”), myalgia, and conjunctivitis may exist.^3,4 Fever usually lasts 5 to 7 days and can be biphasic, with a return of symptoms after the initial resolution as seen in case report 1.⁴  Severe dengue is characterized by capillary leakage, hemorrhage, or end-organ damage.^3-5 The most common bleeding sites are the skin, nose, and gums.

Diagnosis

Bedside evaluation for dengue can be performed with the TT—one of the WHO’s case definitions for dengue.⁶ This is accomplished by placing a manual blood pressure (BP) cuff on the arm and inflating it to halfway between systolic and diastolic BP for 5 minutes. The test is positive for dengue if more than 10 petechiae appear per 1-inch (2.5-cm) square below the antecubital fossa.⁷ Of note, the test has poor sensitivity (51.6%, 95% confidence interval [CI], 33-69), but good specificity (82.4%, 95% CI, 76-87).^7,8 A positive TT combined with leukopenia increases the sensitivity to 93.9%, [95% CI, 89-96].⁷ While not specific to dengue infection, in the right clinical scenario, the TT is a simple bedside test to help confirm the diagnosis and is extremely useful in resource-limited settings. 

During the initial days of illness, the virus may be detected by PCR, as viremia and fever usually correlate. Once defervescence occurs, IgM and then IgG antibodies become detectable. When using these antibody tests to evaluate for dengue, clinicians should be aware of cross-reactivity with other flavivirus infections, such as yellow fever or Japanese encephalitis (including immunological cross-reactivity).¹ New diagnostic modalities include enzyme immunoassays that can detect dengue viral RNA within 24 to 48 hours, and viral antigen-detection kits, which can yield results in less than 1 hour.⁴

Aside from advanced laboratory testing, worsening thrombocytopenia in light of a rising hematocrit can be highly suggestive of dengue. Leukopenia with lymphopenia and mild elevation of hepatic enzymes (typically 2 to 5 times the upper limits of the normal reference range) are also often seen in active infections.¹ The occurrence of these signs in conjunction with a rapid reduction in the platelets often signals transition to the critical phase of plasma leakage.^1,4

Treatment

Treatment of dengue consists of supportive care and transfusion when necessary. The WHO recommends strict observation of patients with suspected dengue who have warning signs of severe disease (eg, abdominal pain, persistent vomiting, mucosal bleeding, lethargy, hepatomegaly, rapid increase in hematocrit with concomitant drop in platelet count). Inpatient treatment centers on judicious fluid management, trending blood count parameters, and monitoring for signs of plasma leakage and hemorrhage. Fluid resuscitation is titrated to optimize central and peripheral circulation and end-organ perfusion. Blood-product administration should be reserved for suspected or severe bleeding.⁴

While dengue fever was the final diagnosis in both of our case presentations, these cases also highlight key diagnostic and treatment dilemmas associated with dengue. The patient in the first case report demonstrated the characteristic biphasic fever seen with dengue—resolution of symptoms on day 3, but then return of fever and symptoms on day 4. Often the dengue-specific antibodies are not formed until after the resolution of fever. This patient represents a classic example of dengue as the serologic studies sent on day 4 of the patient’s illness were negative but then turned positive on day 7, illustrating the need for high clinical suspicion and underscoring the importance of initiating treatment despite laboratory confirmation.

Further, regarding the patient in the second case, though proteinuria, hematuria, acute renal failure, and glomerulonephritis are previously described renal complications of dengue,⁹ a thorough literature search yielded no prior published accounts of renal infarction. Given the patient’s previous healthy status and the lack of other hypothesis as to the mechanism of injury, we suspect this patient’s renal infarction was due to the transient hypercoagulability characteristic of dengue and responsible for other clinical manifestations of the disease.

Conclusion

In addition to more prevalent illnesses such as malaria, acute traveler’s diarrhea, and respiratory tract infections, dengue fever should be included in the differential diagnosis when evaluating a febrile patient who has a history of recent travel to countries where dengue is endemic. A high clinical suspicion, combined with a thorough history and physical examination, is essential to making the diagnosis.

Both of our case reports demonstrate some of the diagnostic limitations in the acute setting, and the breadth of clinical complications that can occur in this complex disease. With the increasing prevalence of dengue fever in North and Central America, it is likely that patients with the disease will present to EDs in the United States. Early diagnosis and awareness of potential complications can lead to timely initiation of life-saving supportive care.