Case Reports

Narrative Description

This Case Report reviews the presentation, the differential diagnosis and the treatment modalities used to treat calciphylaxis. It emphasizes the poor prognosis and that there is inadequate clinical experience to guide a physician as to what the most appropriate treatment is despite promising anecdotal reports about a variety of agents. The report demonstrates that intravenous sodium thiosulfate is tolerated.

Key Points

• Calciphylaxis occurs in 1 to 4% of patients with end stage renal failure.

• Two patterns of presentation are generally recognizedcentral and peripheral.

• Pain is a prominent symptom and eschar formation is usually present.

• The role of surgery is controversial.

• Several promising modalities for the treatment of this condition have been described in anecdotal reports.

Calciphylaxis is a rare condition. It is seen most frequently in patients with chronic kidney disease and can affect any part of the body.14 Calciphylaxis is increasingly being referred to as calcific uremic arteriolopathy as this term more accurately reflects the histology of vascular calcification in small‐ and medium‐sized arteries, intimal arterial hypertrophy, and small vessel thrombosis associated with panniculitis, dermal necrosis, and eschar formation.5 Pain is a prominent symptom. The most effective treatment for this condition remains uncertain.

Case Report

A 68‐year‐old female presented with an 8‐month history of increasing lower extremity edema, and numerous large, painful, necrotic ulcers with an associated foul odor. She had a past medical history of type 2 diabetes mellitus, hypertension, end stage renal disease requiring hemodialysis 3 times a week for the previous 6 months, severe peripheral vascular disease, coronary artery disease for which she had previously undergone coronary artery bypass surgery, multiple myocardial infarctions, and congestive heart failure with an ejection fraction of 20%. She had also suffered from numerous infections including septicemia, endocarditis, and a sternal wound infection in the past with no current evidence of septicemia or endocarditis. The patient was not on calcium supplements, Vitamin D, warfarin or calcium‐containing phosphate binders.

Eight months prior to admission she developed vesicles on the left thigh that slowly progressed to large, extremely painful, violaceous, indurated plaques with central ulceration and eschar (Figure 1). She subsequently developed several smaller lesions with similar morphology on her legs and feet and gangrene of her left big toe (Figure 2). A biopsy from the left thigh was consistent with calciphylaxis with associated necrosis of the deep dermis and subcutaneous tissues. The patient's lesions were aggressively debrided, broad spectrum antibiotics given, and the patient dialyzed with low calcium dialysates. Ultimately intravenous sodium thiosulfate (25 g intravenously, over 60 minutes), was given which she tolerated with no side effect. Sodium thiosulfate is thought to act by forming highly soluble calcium thiosulfate salts and therefore mobilizing tissue calcium.5 Hyperbaric oxygen was contraindicated because of the patient's left ventricular ejection fraction (LVEF) of 20% and previous history of congestive heart failure as this treatment modality may precipitate congestive heart failure in a patient with a low LVEF particularly with a past history of congestive heart failure. Her condition continued to deteriorate and she died a few days after initiation of intravenous sodium thiosulfate infusion secondary to a massive gastrointestinal bleed.

Figure 1

Figure 2

Discussion

The differential diagnosis for painful necrotic cutaneous ulcerations with eschar formation includes: calciphylaxis, cryoglobulinemia, cryofibrinogenema, peripheral vascular disease, embolic phenomenon (endocarditis, septic, cholesterol), warfarin skin necrosis, brown recluse spider bites, hypercoagulable states, hyperoxaluria, and necrotizing vasculitis.14

Calciphylaxis is a rare entity that affects approximately 1% to 4% of end stage renal failure patients.1, 3 The typical patient is a morbidly obese, female with longstanding end stage renal disease, diabetes, hyperphosphatemia and an elevated calcium‐phosphate product usually greater than 60 mg²/dL².1, 3 It has also been described in patients with alcoholic cirrhosis and acute reversible renal failure,6 primary and secondary hyperparathyroidism,7 and metastatic breast cancer.8

Patients typically present with symmetric lesions that evolve from erythematous to violaceous, livedo‐reticularis like patches or plaques with occasional bullae to painful, indurated, necrotic plaques that subsequently ulcerate. The ulcerations are slow to heal and covered with eschar.4, 9

There are 2 patterns of involvement. The central/proximal pattern involves the abdomen, gluteal region, and thighs while the peripheral/distal pattern involves the extremities distal to the elbows and knees.1, 2, 4 The central pattern tends to carry a worse prognosis,9, 10 though this has not been validated in all reports and recent literature suggests that patients with both patterns have the worst prognosis.11

A biopsy may be required to exclude other diagnoses. The histology demonstrates an obliterative vasculopathy secondary to the vascular intimal changes and endovascular fibrosis.12 A suggestive finding is calcification of the medial wall of small‐ and medium‐sized arteries and arterioles with associated intimal hyperplasia and fibrosis. Necrosis of the surrounding tissue, panniculitis, and soft tissue calcification are often present.9, 13 The trauma of the biopsy can lead to worsening of the disease.

Secondary to its association with end stage renal disease, laboratory data often reveals elevated blood urea nitrogen (BUN), creatinine, parathyroid hormone, and calcium‐phosphate product. Bone scans show increased uptake in the subcutaneous calcified plaques.14 X‐rays utilizing mammogram technique have demonstrated arteriolar calcification.15

Besides chronic kidney disease, other potential risk factors include protein C and S deficiencies, obesity, warfarin use, high calcium containing dialysates, liver disease, and systemic corticosteroids.4, 9, 11, 16

Calciphylaxis is a difficult disease to treat with a mortality of 60% to 70%9 and a 1‐year survival rate of 45.8%.11 There is no consistently effective treatment.5 Therapy therefore, is focused on symptom control, debridement, and treatment of infection. Mortality is most commonly due to wound infections and resulting septicemia. Meticulous wound care is important with any infection treated early and aggressively. Though trauma and surgical procedures have been known to precipitate ulcerations, given their high rate of infection early surgical debridement of wounds is often required and has been shown to improve mortality.11, 17 Because of the poor healing of the involved tissues, wounds are often left to close by secondary intention or in some circumstances with vacuum assistance.2

As secondary hyperparathyroidism is common, attempts are often made to lower the calcium‐phosphate product. This often requires parathyroidectomy.18 Calcium containing phosphate binders are avoided and low calcium dialysate used.19 However, the above interventions do not consistently improve mortality.5, 11

Other potential treatments include: hyperbaric oxygen therapy,20 intravenous sodium thiosulfate,14 low‐dose tissue plasminogen activator,21 cinacalcet,22 etidronate disodium,23 and maggots.24 Because of the rarity of the condition, most of the literature to date is anecdotal and based on case reports and small retrospective studies.

Conclusions

As the number of patients who develop chronic kidney disease and require hemodialysis increases, it is likely that the number of patients who develop calciphylaxis will also increase. Hospitalists, besides nephrologists, should therefore become familiar with the presentation of this disease as it is possible, although unproven, that treatment in the early stage of the disease may result in a better response. Although several treatment modalities have been used to treat calcific uremic arteriolopathy or calciphylaxis, it remains unclear what is the best treatment for these patients. Carefully done clinical trials using some of the treatment modalities mentioned will help physicians decide what the most appropriate treatment is for patients with this debilitating and often fatal disease.

Narrative Description

This Case Report reviews the presentation, the differential diagnosis and the treatment modalities used to treat calciphylaxis. It emphasizes the poor prognosis and that there is inadequate clinical experience to guide a physician as to what the most appropriate treatment is despite promising anecdotal reports about a variety of agents. The report demonstrates that intravenous sodium thiosulfate is tolerated.

Key Points

• Calciphylaxis occurs in 1 to 4% of patients with end stage renal failure.

• Two patterns of presentation are generally recognizedcentral and peripheral.

• Pain is a prominent symptom and eschar formation is usually present.

• The role of surgery is controversial.

• Several promising modalities for the treatment of this condition have been described in anecdotal reports.

Calciphylaxis is a rare condition. It is seen most frequently in patients with chronic kidney disease and can affect any part of the body.14 Calciphylaxis is increasingly being referred to as calcific uremic arteriolopathy as this term more accurately reflects the histology of vascular calcification in small‐ and medium‐sized arteries, intimal arterial hypertrophy, and small vessel thrombosis associated with panniculitis, dermal necrosis, and eschar formation.5 Pain is a prominent symptom. The most effective treatment for this condition remains uncertain.

Case Report

A 68‐year‐old female presented with an 8‐month history of increasing lower extremity edema, and numerous large, painful, necrotic ulcers with an associated foul odor. She had a past medical history of type 2 diabetes mellitus, hypertension, end stage renal disease requiring hemodialysis 3 times a week for the previous 6 months, severe peripheral vascular disease, coronary artery disease for which she had previously undergone coronary artery bypass surgery, multiple myocardial infarctions, and congestive heart failure with an ejection fraction of 20%. She had also suffered from numerous infections including septicemia, endocarditis, and a sternal wound infection in the past with no current evidence of septicemia or endocarditis. The patient was not on calcium supplements, Vitamin D, warfarin or calcium‐containing phosphate binders.

Eight months prior to admission she developed vesicles on the left thigh that slowly progressed to large, extremely painful, violaceous, indurated plaques with central ulceration and eschar (Figure 1). She subsequently developed several smaller lesions with similar morphology on her legs and feet and gangrene of her left big toe (Figure 2). A biopsy from the left thigh was consistent with calciphylaxis with associated necrosis of the deep dermis and subcutaneous tissues. The patient's lesions were aggressively debrided, broad spectrum antibiotics given, and the patient dialyzed with low calcium dialysates. Ultimately intravenous sodium thiosulfate (25 g intravenously, over 60 minutes), was given which she tolerated with no side effect. Sodium thiosulfate is thought to act by forming highly soluble calcium thiosulfate salts and therefore mobilizing tissue calcium.5 Hyperbaric oxygen was contraindicated because of the patient's left ventricular ejection fraction (LVEF) of 20% and previous history of congestive heart failure as this treatment modality may precipitate congestive heart failure in a patient with a low LVEF particularly with a past history of congestive heart failure. Her condition continued to deteriorate and she died a few days after initiation of intravenous sodium thiosulfate infusion secondary to a massive gastrointestinal bleed.

Figure 1

Figure 2

Discussion

The differential diagnosis for painful necrotic cutaneous ulcerations with eschar formation includes: calciphylaxis, cryoglobulinemia, cryofibrinogenema, peripheral vascular disease, embolic phenomenon (endocarditis, septic, cholesterol), warfarin skin necrosis, brown recluse spider bites, hypercoagulable states, hyperoxaluria, and necrotizing vasculitis.14

Calciphylaxis is a rare entity that affects approximately 1% to 4% of end stage renal failure patients.1, 3 The typical patient is a morbidly obese, female with longstanding end stage renal disease, diabetes, hyperphosphatemia and an elevated calcium‐phosphate product usually greater than 60 mg²/dL².1, 3 It has also been described in patients with alcoholic cirrhosis and acute reversible renal failure,6 primary and secondary hyperparathyroidism,7 and metastatic breast cancer.8

Patients typically present with symmetric lesions that evolve from erythematous to violaceous, livedo‐reticularis like patches or plaques with occasional bullae to painful, indurated, necrotic plaques that subsequently ulcerate. The ulcerations are slow to heal and covered with eschar.4, 9

There are 2 patterns of involvement. The central/proximal pattern involves the abdomen, gluteal region, and thighs while the peripheral/distal pattern involves the extremities distal to the elbows and knees.1, 2, 4 The central pattern tends to carry a worse prognosis,9, 10 though this has not been validated in all reports and recent literature suggests that patients with both patterns have the worst prognosis.11

A biopsy may be required to exclude other diagnoses. The histology demonstrates an obliterative vasculopathy secondary to the vascular intimal changes and endovascular fibrosis.12 A suggestive finding is calcification of the medial wall of small‐ and medium‐sized arteries and arterioles with associated intimal hyperplasia and fibrosis. Necrosis of the surrounding tissue, panniculitis, and soft tissue calcification are often present.9, 13 The trauma of the biopsy can lead to worsening of the disease.

Secondary to its association with end stage renal disease, laboratory data often reveals elevated blood urea nitrogen (BUN), creatinine, parathyroid hormone, and calcium‐phosphate product. Bone scans show increased uptake in the subcutaneous calcified plaques.14 X‐rays utilizing mammogram technique have demonstrated arteriolar calcification.15

Besides chronic kidney disease, other potential risk factors include protein C and S deficiencies, obesity, warfarin use, high calcium containing dialysates, liver disease, and systemic corticosteroids.4, 9, 11, 16

Calciphylaxis is a difficult disease to treat with a mortality of 60% to 70%9 and a 1‐year survival rate of 45.8%.11 There is no consistently effective treatment.5 Therapy therefore, is focused on symptom control, debridement, and treatment of infection. Mortality is most commonly due to wound infections and resulting septicemia. Meticulous wound care is important with any infection treated early and aggressively. Though trauma and surgical procedures have been known to precipitate ulcerations, given their high rate of infection early surgical debridement of wounds is often required and has been shown to improve mortality.11, 17 Because of the poor healing of the involved tissues, wounds are often left to close by secondary intention or in some circumstances with vacuum assistance.2

As secondary hyperparathyroidism is common, attempts are often made to lower the calcium‐phosphate product. This often requires parathyroidectomy.18 Calcium containing phosphate binders are avoided and low calcium dialysate used.19 However, the above interventions do not consistently improve mortality.5, 11

Other potential treatments include: hyperbaric oxygen therapy,20 intravenous sodium thiosulfate,14 low‐dose tissue plasminogen activator,21 cinacalcet,22 etidronate disodium,23 and maggots.24 Because of the rarity of the condition, most of the literature to date is anecdotal and based on case reports and small retrospective studies.

Conclusions

As the number of patients who develop chronic kidney disease and require hemodialysis increases, it is likely that the number of patients who develop calciphylaxis will also increase. Hospitalists, besides nephrologists, should therefore become familiar with the presentation of this disease as it is possible, although unproven, that treatment in the early stage of the disease may result in a better response. Although several treatment modalities have been used to treat calcific uremic arteriolopathy or calciphylaxis, it remains unclear what is the best treatment for these patients. Carefully done clinical trials using some of the treatment modalities mentioned will help physicians decide what the most appropriate treatment is for patients with this debilitating and often fatal disease.

Narrative Description

This Case Report reviews the presentation, the differential diagnosis and the treatment modalities used to treat calciphylaxis. It emphasizes the poor prognosis and that there is inadequate clinical experience to guide a physician as to what the most appropriate treatment is despite promising anecdotal reports about a variety of agents. The report demonstrates that intravenous sodium thiosulfate is tolerated.

Key Points

• Calciphylaxis occurs in 1 to 4% of patients with end stage renal failure.

• Two patterns of presentation are generally recognizedcentral and peripheral.

• Pain is a prominent symptom and eschar formation is usually present.

• The role of surgery is controversial.

• Several promising modalities for the treatment of this condition have been described in anecdotal reports.

Calciphylaxis is a rare condition. It is seen most frequently in patients with chronic kidney disease and can affect any part of the body.14 Calciphylaxis is increasingly being referred to as calcific uremic arteriolopathy as this term more accurately reflects the histology of vascular calcification in small‐ and medium‐sized arteries, intimal arterial hypertrophy, and small vessel thrombosis associated with panniculitis, dermal necrosis, and eschar formation.5 Pain is a prominent symptom. The most effective treatment for this condition remains uncertain.

Case Report

A 68‐year‐old female presented with an 8‐month history of increasing lower extremity edema, and numerous large, painful, necrotic ulcers with an associated foul odor. She had a past medical history of type 2 diabetes mellitus, hypertension, end stage renal disease requiring hemodialysis 3 times a week for the previous 6 months, severe peripheral vascular disease, coronary artery disease for which she had previously undergone coronary artery bypass surgery, multiple myocardial infarctions, and congestive heart failure with an ejection fraction of 20%. She had also suffered from numerous infections including septicemia, endocarditis, and a sternal wound infection in the past with no current evidence of septicemia or endocarditis. The patient was not on calcium supplements, Vitamin D, warfarin or calcium‐containing phosphate binders.

Eight months prior to admission she developed vesicles on the left thigh that slowly progressed to large, extremely painful, violaceous, indurated plaques with central ulceration and eschar (Figure 1). She subsequently developed several smaller lesions with similar morphology on her legs and feet and gangrene of her left big toe (Figure 2). A biopsy from the left thigh was consistent with calciphylaxis with associated necrosis of the deep dermis and subcutaneous tissues. The patient's lesions were aggressively debrided, broad spectrum antibiotics given, and the patient dialyzed with low calcium dialysates. Ultimately intravenous sodium thiosulfate (25 g intravenously, over 60 minutes), was given which she tolerated with no side effect. Sodium thiosulfate is thought to act by forming highly soluble calcium thiosulfate salts and therefore mobilizing tissue calcium.5 Hyperbaric oxygen was contraindicated because of the patient's left ventricular ejection fraction (LVEF) of 20% and previous history of congestive heart failure as this treatment modality may precipitate congestive heart failure in a patient with a low LVEF particularly with a past history of congestive heart failure. Her condition continued to deteriorate and she died a few days after initiation of intravenous sodium thiosulfate infusion secondary to a massive gastrointestinal bleed.

Figure 1

Figure 2

Discussion

The differential diagnosis for painful necrotic cutaneous ulcerations with eschar formation includes: calciphylaxis, cryoglobulinemia, cryofibrinogenema, peripheral vascular disease, embolic phenomenon (endocarditis, septic, cholesterol), warfarin skin necrosis, brown recluse spider bites, hypercoagulable states, hyperoxaluria, and necrotizing vasculitis.14

Calciphylaxis is a rare entity that affects approximately 1% to 4% of end stage renal failure patients.1, 3 The typical patient is a morbidly obese, female with longstanding end stage renal disease, diabetes, hyperphosphatemia and an elevated calcium‐phosphate product usually greater than 60 mg²/dL².1, 3 It has also been described in patients with alcoholic cirrhosis and acute reversible renal failure,6 primary and secondary hyperparathyroidism,7 and metastatic breast cancer.8

Patients typically present with symmetric lesions that evolve from erythematous to violaceous, livedo‐reticularis like patches or plaques with occasional bullae to painful, indurated, necrotic plaques that subsequently ulcerate. The ulcerations are slow to heal and covered with eschar.4, 9

There are 2 patterns of involvement. The central/proximal pattern involves the abdomen, gluteal region, and thighs while the peripheral/distal pattern involves the extremities distal to the elbows and knees.1, 2, 4 The central pattern tends to carry a worse prognosis,9, 10 though this has not been validated in all reports and recent literature suggests that patients with both patterns have the worst prognosis.11

A biopsy may be required to exclude other diagnoses. The histology demonstrates an obliterative vasculopathy secondary to the vascular intimal changes and endovascular fibrosis.12 A suggestive finding is calcification of the medial wall of small‐ and medium‐sized arteries and arterioles with associated intimal hyperplasia and fibrosis. Necrosis of the surrounding tissue, panniculitis, and soft tissue calcification are often present.9, 13 The trauma of the biopsy can lead to worsening of the disease.

Secondary to its association with end stage renal disease, laboratory data often reveals elevated blood urea nitrogen (BUN), creatinine, parathyroid hormone, and calcium‐phosphate product. Bone scans show increased uptake in the subcutaneous calcified plaques.14 X‐rays utilizing mammogram technique have demonstrated arteriolar calcification.15

Besides chronic kidney disease, other potential risk factors include protein C and S deficiencies, obesity, warfarin use, high calcium containing dialysates, liver disease, and systemic corticosteroids.4, 9, 11, 16

Calciphylaxis is a difficult disease to treat with a mortality of 60% to 70%9 and a 1‐year survival rate of 45.8%.11 There is no consistently effective treatment.5 Therapy therefore, is focused on symptom control, debridement, and treatment of infection. Mortality is most commonly due to wound infections and resulting septicemia. Meticulous wound care is important with any infection treated early and aggressively. Though trauma and surgical procedures have been known to precipitate ulcerations, given their high rate of infection early surgical debridement of wounds is often required and has been shown to improve mortality.11, 17 Because of the poor healing of the involved tissues, wounds are often left to close by secondary intention or in some circumstances with vacuum assistance.2

As secondary hyperparathyroidism is common, attempts are often made to lower the calcium‐phosphate product. This often requires parathyroidectomy.18 Calcium containing phosphate binders are avoided and low calcium dialysate used.19 However, the above interventions do not consistently improve mortality.5, 11

Other potential treatments include: hyperbaric oxygen therapy,20 intravenous sodium thiosulfate,14 low‐dose tissue plasminogen activator,21 cinacalcet,22 etidronate disodium,23 and maggots.24 Because of the rarity of the condition, most of the literature to date is anecdotal and based on case reports and small retrospective studies.

Conclusions

As the number of patients who develop chronic kidney disease and require hemodialysis increases, it is likely that the number of patients who develop calciphylaxis will also increase. Hospitalists, besides nephrologists, should therefore become familiar with the presentation of this disease as it is possible, although unproven, that treatment in the early stage of the disease may result in a better response. Although several treatment modalities have been used to treat calcific uremic arteriolopathy or calciphylaxis, it remains unclear what is the best treatment for these patients. Carefully done clinical trials using some of the treatment modalities mentioned will help physicians decide what the most appropriate treatment is for patients with this debilitating and often fatal disease.

Presentation

An 84 year‐old male with past history of osteoarthritis, extensive degenerative spine disease with spinal stenosis presented to the emergency room with left groin pain accompanied by a foul‐smelling discharge from the acupuncture site. He had been receiving regular physical therapy and acupuncture sessions for the past 6 months prior to his presentation. One and a half weeks prior to presentation, needles were inserted over the left groin as part of his acupuncture regimen. The patient described the acupuncture needles originating from a single use, unopened package. Additionally, the patient states his skin was cleaned with an antiseptic solution prior to insertion. Within 3 days, he developed generalized weakness, malaise with localized swelling, erythema, and warmth over the left groin area. His primary care physician performed an incision and drainage and prescribed ciprofloxacin. The patient continued to experience worsening fatigue, difficulty ambulating, ongoing purulent drainage, and consequently presented to the hospital for further evaluation. The patient has an allergy to penicillin but no history of diabetes. He quit smoking 40 years ago and has occasional alcohol intake. Surgical history includes bilateral knee replacement 15 years ago for osteoarthritis and right inguinal hernia repair and appendectomy 60 years ago.

On physical examination the patient had a temperature of 96.8F, pulse of 88 beats per minute, blood pressure of 97/63 mm Hg, and an oxygen saturation of 98% on room air. There was extensive swelling, erythema, and induration of the left anterior and proximal inguinal area, with a 2‐cm malodorous ulcer over the midline thigh. No crepitation or mass was palpable. Range of motion at the hip on the affected limb was limited due to pain. Distal pulses on the lower extremity were present and equal bilaterally. Laboratory examination revealed white blood cell (WBC) = 16.4 with 41% bands. Blood cultures were sent and intravenous vancomycin, ciprofloxacin, clindamycin, and metronidazole were started. A computed tomography (CT)‐scan of the left lower extremity was performed and revealed skin thickening and reticulation of the subcutaneous tissues edema extending from the left groin to the left buttock. Several foci of gas were present within the soft tissues with the largest in the lateral aspect of the buttocks of gas in the soft tissues (Figure 1). The Laboratory Risk Indicator for Necrotizing Fasciitis, the patient scored a 3 out of a possible 13 points. The diagnosis of necrotizing fasciitis was made based on clinical findings and radiographic imaging.

Figure 1

Assessment

Patient became significantly hypotensive which required vasopressor support. He underwent surgical exploration of the left inguinal area. During surgery, tender crepitation of the antero‐lateral aspect of the thigh was noted. Extensive debridement with fasciotomy was performed. Tissue was sent for histopathological analysis and gram‐stain. A negative‐pressure wound dressing was placed over the defect. Post‐operatively, patient required intubation and continued vasopressor support. On post‐operative day 3, patient was extubated. Wound culture report revealed gram negative rods and Enterococcus faecalis which was sensitive to the patients' current antibiotic regimen. Clindamycin was discontinued. The patient was discharged to a subacute rehabilitation facility and returned for a split thickness skin graft 2 months after initial presentation.

Necrotizing fasciitis is a deep‐seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat. Presenting symptoms include pain, erythema, or bullae formation at the site of infection. Systemic symptoms such as fever, malaise, and myalgias may also be present at the time of presentation. Two types of necrotizing fasciitis are noted to occur. Type 1 is a mixed infection with a predominance of anaerobes1 and carries a 21% mortality.2 It is common post‐operatively and in patients with diabetes. In type 2 necrotizing fasciitis, Group‐A streptococcus was the most common cause of monomicrobial necrotizing fasciitis2 and mortality can be as high as 30%.3 Risk factors for the development of fasciitis include immunosuppression, diabetes, surgery, or penetrating injuries. Gas on soft tissue x‐rays, CT scan, or magnetic resonance imaging (MRI) is a highly specific but insensitive finding and is common in type I necrotizing fasciitis.

The patient in this case likely developed type I necrotizing fasciitis due to the presence of gas on CT scan and polymicrobial culture findings.

Diagnosis

A PubMed search of necrotizing fasciitis and acupuncture reveals only one case report, in which a diabetic patient underwent an unsterile acupuncture consultation.4 To our knowledge, we are the first to describe necrotizing fasciitis occurring in a nondiabetic patient who underwent a sterile acupuncture technique.

Given the lack of an explainable causal relationship regarding the pathogenesis of necrotizing fasciitis in our patient, it appears to be due to the acupuncture needle placement. The patient had no other history of abscesses, trauma and other portals of entry. The patient's presentation, temporal relation of the site of acupuncture, and the development of infection prompted a high index of suspicion as acupuncture as the main etiology.

Management

Treatment of necrotizing fasciitis includes early and aggressive surgical debridement. Multiple antibiotic regimens may be necessary due to the polymicrobial nature of the infection. In our patient, ciprofloxacin was initiated for broadened gram negative coverage, vancomycin for community acquired methicillin‐resistant Staphylococcus aureus (MRSA) and metronidazole for anaerobic coverage. Clindamycin was initiated due to concerns of toxin production, but was discontinued as the patient's condition improved.

Although complications of acupuncture may be rare, there exists the potential to cause life threatening complications. Necrotizing fasciitis has been observed as an adverse effect of acupuncture in a single diabetic patient,4 but can develop in nondiabetic individuals, such as in our patient.

Presentation

An 84 year‐old male with past history of osteoarthritis, extensive degenerative spine disease with spinal stenosis presented to the emergency room with left groin pain accompanied by a foul‐smelling discharge from the acupuncture site. He had been receiving regular physical therapy and acupuncture sessions for the past 6 months prior to his presentation. One and a half weeks prior to presentation, needles were inserted over the left groin as part of his acupuncture regimen. The patient described the acupuncture needles originating from a single use, unopened package. Additionally, the patient states his skin was cleaned with an antiseptic solution prior to insertion. Within 3 days, he developed generalized weakness, malaise with localized swelling, erythema, and warmth over the left groin area. His primary care physician performed an incision and drainage and prescribed ciprofloxacin. The patient continued to experience worsening fatigue, difficulty ambulating, ongoing purulent drainage, and consequently presented to the hospital for further evaluation. The patient has an allergy to penicillin but no history of diabetes. He quit smoking 40 years ago and has occasional alcohol intake. Surgical history includes bilateral knee replacement 15 years ago for osteoarthritis and right inguinal hernia repair and appendectomy 60 years ago.

On physical examination the patient had a temperature of 96.8F, pulse of 88 beats per minute, blood pressure of 97/63 mm Hg, and an oxygen saturation of 98% on room air. There was extensive swelling, erythema, and induration of the left anterior and proximal inguinal area, with a 2‐cm malodorous ulcer over the midline thigh. No crepitation or mass was palpable. Range of motion at the hip on the affected limb was limited due to pain. Distal pulses on the lower extremity were present and equal bilaterally. Laboratory examination revealed white blood cell (WBC) = 16.4 with 41% bands. Blood cultures were sent and intravenous vancomycin, ciprofloxacin, clindamycin, and metronidazole were started. A computed tomography (CT)‐scan of the left lower extremity was performed and revealed skin thickening and reticulation of the subcutaneous tissues edema extending from the left groin to the left buttock. Several foci of gas were present within the soft tissues with the largest in the lateral aspect of the buttocks of gas in the soft tissues (Figure 1). The Laboratory Risk Indicator for Necrotizing Fasciitis, the patient scored a 3 out of a possible 13 points. The diagnosis of necrotizing fasciitis was made based on clinical findings and radiographic imaging.

Figure 1

Assessment

Patient became significantly hypotensive which required vasopressor support. He underwent surgical exploration of the left inguinal area. During surgery, tender crepitation of the antero‐lateral aspect of the thigh was noted. Extensive debridement with fasciotomy was performed. Tissue was sent for histopathological analysis and gram‐stain. A negative‐pressure wound dressing was placed over the defect. Post‐operatively, patient required intubation and continued vasopressor support. On post‐operative day 3, patient was extubated. Wound culture report revealed gram negative rods and Enterococcus faecalis which was sensitive to the patients' current antibiotic regimen. Clindamycin was discontinued. The patient was discharged to a subacute rehabilitation facility and returned for a split thickness skin graft 2 months after initial presentation.

Necrotizing fasciitis is a deep‐seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat. Presenting symptoms include pain, erythema, or bullae formation at the site of infection. Systemic symptoms such as fever, malaise, and myalgias may also be present at the time of presentation. Two types of necrotizing fasciitis are noted to occur. Type 1 is a mixed infection with a predominance of anaerobes1 and carries a 21% mortality.2 It is common post‐operatively and in patients with diabetes. In type 2 necrotizing fasciitis, Group‐A streptococcus was the most common cause of monomicrobial necrotizing fasciitis2 and mortality can be as high as 30%.3 Risk factors for the development of fasciitis include immunosuppression, diabetes, surgery, or penetrating injuries. Gas on soft tissue x‐rays, CT scan, or magnetic resonance imaging (MRI) is a highly specific but insensitive finding and is common in type I necrotizing fasciitis.

The patient in this case likely developed type I necrotizing fasciitis due to the presence of gas on CT scan and polymicrobial culture findings.

Diagnosis

A PubMed search of necrotizing fasciitis and acupuncture reveals only one case report, in which a diabetic patient underwent an unsterile acupuncture consultation.4 To our knowledge, we are the first to describe necrotizing fasciitis occurring in a nondiabetic patient who underwent a sterile acupuncture technique.

Given the lack of an explainable causal relationship regarding the pathogenesis of necrotizing fasciitis in our patient, it appears to be due to the acupuncture needle placement. The patient had no other history of abscesses, trauma and other portals of entry. The patient's presentation, temporal relation of the site of acupuncture, and the development of infection prompted a high index of suspicion as acupuncture as the main etiology.

Management

Treatment of necrotizing fasciitis includes early and aggressive surgical debridement. Multiple antibiotic regimens may be necessary due to the polymicrobial nature of the infection. In our patient, ciprofloxacin was initiated for broadened gram negative coverage, vancomycin for community acquired methicillin‐resistant Staphylococcus aureus (MRSA) and metronidazole for anaerobic coverage. Clindamycin was initiated due to concerns of toxin production, but was discontinued as the patient's condition improved.

Although complications of acupuncture may be rare, there exists the potential to cause life threatening complications. Necrotizing fasciitis has been observed as an adverse effect of acupuncture in a single diabetic patient,4 but can develop in nondiabetic individuals, such as in our patient.

Presentation

An 84 year‐old male with past history of osteoarthritis, extensive degenerative spine disease with spinal stenosis presented to the emergency room with left groin pain accompanied by a foul‐smelling discharge from the acupuncture site. He had been receiving regular physical therapy and acupuncture sessions for the past 6 months prior to his presentation. One and a half weeks prior to presentation, needles were inserted over the left groin as part of his acupuncture regimen. The patient described the acupuncture needles originating from a single use, unopened package. Additionally, the patient states his skin was cleaned with an antiseptic solution prior to insertion. Within 3 days, he developed generalized weakness, malaise with localized swelling, erythema, and warmth over the left groin area. His primary care physician performed an incision and drainage and prescribed ciprofloxacin. The patient continued to experience worsening fatigue, difficulty ambulating, ongoing purulent drainage, and consequently presented to the hospital for further evaluation. The patient has an allergy to penicillin but no history of diabetes. He quit smoking 40 years ago and has occasional alcohol intake. Surgical history includes bilateral knee replacement 15 years ago for osteoarthritis and right inguinal hernia repair and appendectomy 60 years ago.

On physical examination the patient had a temperature of 96.8F, pulse of 88 beats per minute, blood pressure of 97/63 mm Hg, and an oxygen saturation of 98% on room air. There was extensive swelling, erythema, and induration of the left anterior and proximal inguinal area, with a 2‐cm malodorous ulcer over the midline thigh. No crepitation or mass was palpable. Range of motion at the hip on the affected limb was limited due to pain. Distal pulses on the lower extremity were present and equal bilaterally. Laboratory examination revealed white blood cell (WBC) = 16.4 with 41% bands. Blood cultures were sent and intravenous vancomycin, ciprofloxacin, clindamycin, and metronidazole were started. A computed tomography (CT)‐scan of the left lower extremity was performed and revealed skin thickening and reticulation of the subcutaneous tissues edema extending from the left groin to the left buttock. Several foci of gas were present within the soft tissues with the largest in the lateral aspect of the buttocks of gas in the soft tissues (Figure 1). The Laboratory Risk Indicator for Necrotizing Fasciitis, the patient scored a 3 out of a possible 13 points. The diagnosis of necrotizing fasciitis was made based on clinical findings and radiographic imaging.

Figure 1

Assessment

Patient became significantly hypotensive which required vasopressor support. He underwent surgical exploration of the left inguinal area. During surgery, tender crepitation of the antero‐lateral aspect of the thigh was noted. Extensive debridement with fasciotomy was performed. Tissue was sent for histopathological analysis and gram‐stain. A negative‐pressure wound dressing was placed over the defect. Post‐operatively, patient required intubation and continued vasopressor support. On post‐operative day 3, patient was extubated. Wound culture report revealed gram negative rods and Enterococcus faecalis which was sensitive to the patients' current antibiotic regimen. Clindamycin was discontinued. The patient was discharged to a subacute rehabilitation facility and returned for a split thickness skin graft 2 months after initial presentation.

Necrotizing fasciitis is a deep‐seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat. Presenting symptoms include pain, erythema, or bullae formation at the site of infection. Systemic symptoms such as fever, malaise, and myalgias may also be present at the time of presentation. Two types of necrotizing fasciitis are noted to occur. Type 1 is a mixed infection with a predominance of anaerobes1 and carries a 21% mortality.2 It is common post‐operatively and in patients with diabetes. In type 2 necrotizing fasciitis, Group‐A streptococcus was the most common cause of monomicrobial necrotizing fasciitis2 and mortality can be as high as 30%.3 Risk factors for the development of fasciitis include immunosuppression, diabetes, surgery, or penetrating injuries. Gas on soft tissue x‐rays, CT scan, or magnetic resonance imaging (MRI) is a highly specific but insensitive finding and is common in type I necrotizing fasciitis.

The patient in this case likely developed type I necrotizing fasciitis due to the presence of gas on CT scan and polymicrobial culture findings.

Diagnosis

A PubMed search of necrotizing fasciitis and acupuncture reveals only one case report, in which a diabetic patient underwent an unsterile acupuncture consultation.4 To our knowledge, we are the first to describe necrotizing fasciitis occurring in a nondiabetic patient who underwent a sterile acupuncture technique.

Given the lack of an explainable causal relationship regarding the pathogenesis of necrotizing fasciitis in our patient, it appears to be due to the acupuncture needle placement. The patient had no other history of abscesses, trauma and other portals of entry. The patient's presentation, temporal relation of the site of acupuncture, and the development of infection prompted a high index of suspicion as acupuncture as the main etiology.

Management

Treatment of necrotizing fasciitis includes early and aggressive surgical debridement. Multiple antibiotic regimens may be necessary due to the polymicrobial nature of the infection. In our patient, ciprofloxacin was initiated for broadened gram negative coverage, vancomycin for community acquired methicillin‐resistant Staphylococcus aureus (MRSA) and metronidazole for anaerobic coverage. Clindamycin was initiated due to concerns of toxin production, but was discontinued as the patient's condition improved.

Although complications of acupuncture may be rare, there exists the potential to cause life threatening complications. Necrotizing fasciitis has been observed as an adverse effect of acupuncture in a single diabetic patient,4 but can develop in nondiabetic individuals, such as in our patient.

Hospitalists frequently diagnose and treat lower extremity deep venous thrombosis (DVT). Patients presenting with acute DVT or chronic venous stasis of the left leg can have an underlying anatomic anomaly known as iliac vein compression syndrome (ICS), May‐Thurner syndrome, or Cockett syndrome in Europe. In this condition, the right iliac artery overlies the left iliac vein, causing extrinsic compression of the vein (Figure 1). 1 This compression and accompanying intraluminal changes predisposes patients to left‐sided lower extremity DVT.2 Failure to recognize and treat this anomaly in patients with acute thrombosis can result in serious vascular sequelae and chronic left leg symptoms.3 A high clinical suspicion should be maintained in young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. The following report is a case of ICS in a young male recognized and treated early by aggressive diagnostic and therapeutic interventions.

Figure 1

Case Report

A 19‐year‐old man presented to the ER with sudden onset of left lower extremity swelling and pain 5 days after a fall. He had no known risk factors for DVT. On physical examination his left leg was dusky, swollen, and tender from his groin to his ankle, with good arterial pulses. Duplex ultra‐sonogram of the leg showed a clot in the femoral vein extending up the popliteal vein. Following a venogram, he underwent mechanical thrombectomy and regional thrombolysis. A repeat venogram showed an irregular narrowing of the left iliac vein and a tubular filling defect at the junction of the inferior vena cava and common iliac veins, suggestive of external compression from the right common iliac artery. The patient underwent successful angioplasty and stenting of the common iliac vein. He was treated with intravenous heparin, warfarin and clopidogrel. His hypercoagulable work‐up was inconclusive.

Discussion

In 1956, May and Thurner 1 brought clinical attention to ICS. They hypothesized that an abnormal compression of the left iliac vein by an overriding right iliac arterypresent in 22% of a series of 430 cadaversled to an intraluminal filling defect in the vein. The chronic extrinsic compression and pulsing force from the overlying artery results in endothelial irritation and formation of venous spurs (fibrous vascular lesions) in the intimal layer of the vein.1 Following the principles of Virchow's triad, this endothelial injury propagates the formation of a thrombus. Subsequent studies by Kim et al.4 suggest that there are 3 stages involved in the pathogenesis of thrombosis in ICS: asymptomatic vein compression, venous spur formation, and finally DVT formation.4, 5 It is estimated that 1 to 3 out of 1000 individuals with this malformation develop DVT each year.5, 6

Patients with ICS may present to the emergency or ambulatory setting in either an acute or chronic phase. The acute phase is the actual episode of thrombosis. Symptoms include left leg pain and swelling up to the groin. In rare cases, pulmonary emboli may be the initial presentation. A lifelong chronic phase can follow if undiagnosed, resulting in pain and swelling of the entire left leg, venous claudication, recurrent thrombosis, pigmentation changes, and ulceration. 3

The typical ICS patient is a woman between 18 and 30 years old, 3 possibly due to the developmental changes in the pelvic structures in preparation for child‐bearing.2 Many patients also present after pregnancy; increased lordosis during pregnancy may put additional strain on the anatomic lesion.3 Nevertheless, Steinberg and Jacocks7 reported that out of 127 patients, 38 (30%) were male. Thus, it is critical not to overlook ICS as a possible cause of thrombosis in male patients.

The urgency in diagnosing this anatomic variation lies in the distinct need for more aggressive treatment than that required for a typical DVT. While Doppler ultrasound is typically the first diagnostic test performed in this patient population, it is not specific. For patients with physical exam findings highly suspicious of ICS, venography and magnetic resonance venography are superior modalities to make a definitive diagnosis of the syndrome. 8 In ICS, these studies will reveal left common iliac vein narrowing with intraluminal changes suggestive of spur formation.2

Due to the mechanical nature of ICS pathology, anticoagulation therapy alone is ineffective. ICS prevents recanalization in 70% to 80% of patients and up to 40% will have continued clot propagation. 5, 7 More aggressive treatment using endovascular techniques such as the combination of thrombectomy, angioplasty, and intraluminal stenting have proven to be the most efficacious treatment modality for ICS.9 A study by AbuRahma et al.10 demonstrated that one year following this aggressive combination, patency rate was 83% (vs. 24% following thrombectomy alone).

Conclusion

The anatomic anomaly present in ICS was identified by CT in as many as two‐thirds of an asymptomatic patient population studied by Kibbe et al. 12 Although a common structural anomaly, it is important to note that only 1 to 3 out of 1000 individuals with this malformation develop DVT annually. ICS should be included in the differential diagnosis of all young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. If the mechanical compression is not diagnosed and treated, the syndrome can develop into a life‐long chronic phase with multiple complications.2 It is therefore critical that aggressive diagnostic and therapeutic interventions be implemented immediately upon suspicion of ICS.

Hospitalists frequently diagnose and treat lower extremity deep venous thrombosis (DVT). Patients presenting with acute DVT or chronic venous stasis of the left leg can have an underlying anatomic anomaly known as iliac vein compression syndrome (ICS), May‐Thurner syndrome, or Cockett syndrome in Europe. In this condition, the right iliac artery overlies the left iliac vein, causing extrinsic compression of the vein (Figure 1). 1 This compression and accompanying intraluminal changes predisposes patients to left‐sided lower extremity DVT.2 Failure to recognize and treat this anomaly in patients with acute thrombosis can result in serious vascular sequelae and chronic left leg symptoms.3 A high clinical suspicion should be maintained in young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. The following report is a case of ICS in a young male recognized and treated early by aggressive diagnostic and therapeutic interventions.

Figure 1

Case Report

A 19‐year‐old man presented to the ER with sudden onset of left lower extremity swelling and pain 5 days after a fall. He had no known risk factors for DVT. On physical examination his left leg was dusky, swollen, and tender from his groin to his ankle, with good arterial pulses. Duplex ultra‐sonogram of the leg showed a clot in the femoral vein extending up the popliteal vein. Following a venogram, he underwent mechanical thrombectomy and regional thrombolysis. A repeat venogram showed an irregular narrowing of the left iliac vein and a tubular filling defect at the junction of the inferior vena cava and common iliac veins, suggestive of external compression from the right common iliac artery. The patient underwent successful angioplasty and stenting of the common iliac vein. He was treated with intravenous heparin, warfarin and clopidogrel. His hypercoagulable work‐up was inconclusive.

Discussion

In 1956, May and Thurner 1 brought clinical attention to ICS. They hypothesized that an abnormal compression of the left iliac vein by an overriding right iliac arterypresent in 22% of a series of 430 cadaversled to an intraluminal filling defect in the vein. The chronic extrinsic compression and pulsing force from the overlying artery results in endothelial irritation and formation of venous spurs (fibrous vascular lesions) in the intimal layer of the vein.1 Following the principles of Virchow's triad, this endothelial injury propagates the formation of a thrombus. Subsequent studies by Kim et al.4 suggest that there are 3 stages involved in the pathogenesis of thrombosis in ICS: asymptomatic vein compression, venous spur formation, and finally DVT formation.4, 5 It is estimated that 1 to 3 out of 1000 individuals with this malformation develop DVT each year.5, 6

Patients with ICS may present to the emergency or ambulatory setting in either an acute or chronic phase. The acute phase is the actual episode of thrombosis. Symptoms include left leg pain and swelling up to the groin. In rare cases, pulmonary emboli may be the initial presentation. A lifelong chronic phase can follow if undiagnosed, resulting in pain and swelling of the entire left leg, venous claudication, recurrent thrombosis, pigmentation changes, and ulceration. 3

The typical ICS patient is a woman between 18 and 30 years old, 3 possibly due to the developmental changes in the pelvic structures in preparation for child‐bearing.2 Many patients also present after pregnancy; increased lordosis during pregnancy may put additional strain on the anatomic lesion.3 Nevertheless, Steinberg and Jacocks7 reported that out of 127 patients, 38 (30%) were male. Thus, it is critical not to overlook ICS as a possible cause of thrombosis in male patients.

The urgency in diagnosing this anatomic variation lies in the distinct need for more aggressive treatment than that required for a typical DVT. While Doppler ultrasound is typically the first diagnostic test performed in this patient population, it is not specific. For patients with physical exam findings highly suspicious of ICS, venography and magnetic resonance venography are superior modalities to make a definitive diagnosis of the syndrome. 8 In ICS, these studies will reveal left common iliac vein narrowing with intraluminal changes suggestive of spur formation.2

Due to the mechanical nature of ICS pathology, anticoagulation therapy alone is ineffective. ICS prevents recanalization in 70% to 80% of patients and up to 40% will have continued clot propagation. 5, 7 More aggressive treatment using endovascular techniques such as the combination of thrombectomy, angioplasty, and intraluminal stenting have proven to be the most efficacious treatment modality for ICS.9 A study by AbuRahma et al.10 demonstrated that one year following this aggressive combination, patency rate was 83% (vs. 24% following thrombectomy alone).

Conclusion

The anatomic anomaly present in ICS was identified by CT in as many as two‐thirds of an asymptomatic patient population studied by Kibbe et al. 12 Although a common structural anomaly, it is important to note that only 1 to 3 out of 1000 individuals with this malformation develop DVT annually. ICS should be included in the differential diagnosis of all young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. If the mechanical compression is not diagnosed and treated, the syndrome can develop into a life‐long chronic phase with multiple complications.2 It is therefore critical that aggressive diagnostic and therapeutic interventions be implemented immediately upon suspicion of ICS.

Hospitalists frequently diagnose and treat lower extremity deep venous thrombosis (DVT). Patients presenting with acute DVT or chronic venous stasis of the left leg can have an underlying anatomic anomaly known as iliac vein compression syndrome (ICS), May‐Thurner syndrome, or Cockett syndrome in Europe. In this condition, the right iliac artery overlies the left iliac vein, causing extrinsic compression of the vein (Figure 1). 1 This compression and accompanying intraluminal changes predisposes patients to left‐sided lower extremity DVT.2 Failure to recognize and treat this anomaly in patients with acute thrombosis can result in serious vascular sequelae and chronic left leg symptoms.3 A high clinical suspicion should be maintained in young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. The following report is a case of ICS in a young male recognized and treated early by aggressive diagnostic and therapeutic interventions.

Figure 1

Case Report

A 19‐year‐old man presented to the ER with sudden onset of left lower extremity swelling and pain 5 days after a fall. He had no known risk factors for DVT. On physical examination his left leg was dusky, swollen, and tender from his groin to his ankle, with good arterial pulses. Duplex ultra‐sonogram of the leg showed a clot in the femoral vein extending up the popliteal vein. Following a venogram, he underwent mechanical thrombectomy and regional thrombolysis. A repeat venogram showed an irregular narrowing of the left iliac vein and a tubular filling defect at the junction of the inferior vena cava and common iliac veins, suggestive of external compression from the right common iliac artery. The patient underwent successful angioplasty and stenting of the common iliac vein. He was treated with intravenous heparin, warfarin and clopidogrel. His hypercoagulable work‐up was inconclusive.

Discussion

In 1956, May and Thurner 1 brought clinical attention to ICS. They hypothesized that an abnormal compression of the left iliac vein by an overriding right iliac arterypresent in 22% of a series of 430 cadaversled to an intraluminal filling defect in the vein. The chronic extrinsic compression and pulsing force from the overlying artery results in endothelial irritation and formation of venous spurs (fibrous vascular lesions) in the intimal layer of the vein.1 Following the principles of Virchow's triad, this endothelial injury propagates the formation of a thrombus. Subsequent studies by Kim et al.4 suggest that there are 3 stages involved in the pathogenesis of thrombosis in ICS: asymptomatic vein compression, venous spur formation, and finally DVT formation.4, 5 It is estimated that 1 to 3 out of 1000 individuals with this malformation develop DVT each year.5, 6

Patients with ICS may present to the emergency or ambulatory setting in either an acute or chronic phase. The acute phase is the actual episode of thrombosis. Symptoms include left leg pain and swelling up to the groin. In rare cases, pulmonary emboli may be the initial presentation. A lifelong chronic phase can follow if undiagnosed, resulting in pain and swelling of the entire left leg, venous claudication, recurrent thrombosis, pigmentation changes, and ulceration. 3

The typical ICS patient is a woman between 18 and 30 years old, 3 possibly due to the developmental changes in the pelvic structures in preparation for child‐bearing.2 Many patients also present after pregnancy; increased lordosis during pregnancy may put additional strain on the anatomic lesion.3 Nevertheless, Steinberg and Jacocks7 reported that out of 127 patients, 38 (30%) were male. Thus, it is critical not to overlook ICS as a possible cause of thrombosis in male patients.

The urgency in diagnosing this anatomic variation lies in the distinct need for more aggressive treatment than that required for a typical DVT. While Doppler ultrasound is typically the first diagnostic test performed in this patient population, it is not specific. For patients with physical exam findings highly suspicious of ICS, venography and magnetic resonance venography are superior modalities to make a definitive diagnosis of the syndrome. 8 In ICS, these studies will reveal left common iliac vein narrowing with intraluminal changes suggestive of spur formation.2

Due to the mechanical nature of ICS pathology, anticoagulation therapy alone is ineffective. ICS prevents recanalization in 70% to 80% of patients and up to 40% will have continued clot propagation. 5, 7 More aggressive treatment using endovascular techniques such as the combination of thrombectomy, angioplasty, and intraluminal stenting have proven to be the most efficacious treatment modality for ICS.9 A study by AbuRahma et al.10 demonstrated that one year following this aggressive combination, patency rate was 83% (vs. 24% following thrombectomy alone).

Conclusion

The anatomic anomaly present in ICS was identified by CT in as many as two‐thirds of an asymptomatic patient population studied by Kibbe et al. 12 Although a common structural anomaly, it is important to note that only 1 to 3 out of 1000 individuals with this malformation develop DVT annually. ICS should be included in the differential diagnosis of all young individuals presenting with proximal left leg DVT with or without hypercoagulable risk factors. If the mechanical compression is not diagnosed and treated, the syndrome can develop into a life‐long chronic phase with multiple complications.2 It is therefore critical that aggressive diagnostic and therapeutic interventions be implemented immediately upon suspicion of ICS.

Recurrent bacterial meningitis (RBM), particularly when caused by Streptococcus pneumoniae, warrants an aggressive and thorough evaluation to exclude transdural communication. We present an unusual case of RBM as a late manifestation of a traumatic head injury sustained 10 years prior and describe presentation, etiology, diagnosis, and treatment options for RBM.

Case Report

A middle‐aged woman with type 2 diabetes mellitus, hypertension, and a prior history of S. pneumoniae meningitis 1 year earlier, presented to an outside hospital with complaints of fever, headache, and change in mental status. Materials for basic laboratory tests and blood cultures were drawn in the Emergency Department; these showed diabetic ketoacidosis. Computed tomography (CT) scan of the head was negative and a lumbar puncture (LP) was attempted, but was unsuccessful. The patient was started on intravenous insulin drip, vancomycin, and ceftriaxone and was transported to our facility via Life‐Flight. She also developed acute respiratory failure requiring mechanical ventilation.

After arrival, the patient had a normal repeat CT scan of her head and a successful LP. Cerebrospinal fluid (CSF) revealed 9064 white blood cells (WBCs)/mm³ with 77% neutrophils and 9% lymphocytes, protein concentration of 275 mg/dL, and glucose of 93 mg/dL. CSF culture and Gram stain were negative, while 1 blood culture drawn at the outside hospital grew penicillin‐resistant S. pneumoniae (MIC 2 g/mL). WBC count was 9660/mm³ with 45% band forms. Bacterial meningitis was confirmed and the patient was continued on intravenous antibiotics and insulin drip. Additional laboratory studies revealed normal complement levels and a negative human immunodeficiency virus (HIV) 1 and HIV 2 antibody screen. The patient was extubated in 48 hours. and was treated with a total of 2 weeks of ceftriaxone and vancomycin for penicillin‐resistant S. pneumoniae meningitis.

The patient had an uneventful full recovery and was discharged from the hospital with neurosurgery follow‐up. The neurosurgeon ordered a CT scan of the facial bones, which revealed an irregular calcification in the right frontal sinus adjacent to the cribriform plate and thinning of the posterior wall of the sinus. Upon requestioning at a subsequent neurosurgical appointment, the patient recalled being an unrestrained passenger and striking her head against the windshield in a motor vehicle accident (MVA) approximately 10 years ago. Ever since the MVA, she noticed intermittent postnasal discharge while recumbent. However, she never sought a medical opinion and denied complaints of anterior rhinorrhea.

A CT cisternography confirmed the presence of CSF leakage with contrast accumulation via a defect in the right paramedian cribriform plate. Contrast opacification was seen in the fovea ethmoidalis extending into the right frontal sinus (Figure 1). The patient subsequently underwent transnasal endoscopic CSF leak repair (Figure 2). The postoperative cisternogram did not reveal the transdural communication. However a follow‐up cisternogram performed 3 months later demonstrated a recurrent CSF leak.

Figure 1

Figure 2

The patient was rehospitalized with grand‐mal seizures and a third episode of S. pneumoniae meningitis, this time with a penicillin‐sensitive strain. She was treated with a 2‐week course of ceftriaxone and also received heptavalent pneumococcal vaccine to supplement the 23‐valent pneumococcal vaccine. Two weeks after the hospital discharge, the patient underwent successful bifrontal transcranial repair. Currently, she has been disease‐free for 3 months and is followed closely by neurosurgery as an outpatient.

Discussion

After immune deficiency is ruled out, it is essential to evaluate for transdural communication between the subarachnoid space and the base of the skull resulting in a CSF leak as a cause for RBM. Meningitis secondary to a CSF leak is most commonly caused by S. pneumoniae, followed by Neisseria meningitidis and Haemophilus influenzae.1 Complement and immunoglobulin subclass defects may also predispose to RBM.2, 3

A recent case series by Adriani et al.4 suggested that as many as 77% of patients with RBM have an identifiable risk factor such as a remote head injury or CSF leakage. CSF rhinorrhea is most often secondary to trauma, occurring in approximately 1% to 3% of all blunt head injuries.2 Accidental falls, MVAs, altercations, and gunshot wounds are also commonly responsible.3 Nontraumatic CSF leaks are very rare but may be secondary to spontaneous, congenital, or iatrogenic etiologies.1, 3 Spontaneous CSF leaks could also occur due to violent sneezing or coughing.1, 3 Congenital defects include weakened preformed pathways, failure of germ layer closures, and bone imperfections.1, 3 Infrequently, CSF leak can be a complication of intracranial, otologic, nasal, or paranasal sinus surgeries.1, 3 Other rarer etiologies include intracranial tumors and hydrocephalus.1, 3

Bacterial meningitis due to traumatic CSF leak can present within 24 hours to as long as several decades after the development of the leak.2, 3 Along with the classic symptoms and signs of meningitis, including fever, headache, neck stiffness, change in sensorium, seizures, and vomiting, patients may also present with CSF rhinorrhea, CSF otorrhea, hearing impairment, or cranial injury residua.3, 5 It is important to note that CSF rhinorrhea and otorrhea are not always present in cases of chronic, posttraumatic CSF leaks.

The visualization of a fracture or bony dehiscence is very difficult but critical for identification and surgical repair. Frontal and ethmoid sinuses and cribriform plate are common fracture sites.1, 3, 5 CSF leakage may be from the anterior, middle, or posterior compartments, eventually ending in the nasal cavity.1, 3, 5 Various imaging modalities, including contrast cisternogram, high‐resolution CT, fluorescein nasal endoscopy, and magnetic resonance imaging (MRI) have been advocated for diagnosing the source of CSF leak with variable sensitivity and specificity.6 High‐resolution CT helps in identifying surgical anatomy and bony defects whereas contrast cisternography is confirmatory when the CSF leak is active.1, 6 Protein electrophoresis demonstrating 2 electrophoretically separate transferrin bands confirms CSF.7

In patients with persistent CSF rhinorrhea, there is a 19% overall risk of meningitis with an annual incidence of 0.3 meningitis episodes per year.8 The risk of meningitis is the greatest in the first year following the onset of a CSF leak.8 Generally, patients with posttraumatic CSF leak lasting more than 7 to 10 days need surgical repair to decrease their risk of bacterial meningitis.1, 3, 5 Endoscopic surgical correction with a success rate of 90% is an effective treatment for CSF leak and involves placement of a temporary lumbar drain in addition to endonasal duraplasty performed with the aid of microscope and/or nasoscope.9 Complicated anterior cranial base fractures are not as amenable to endoscopic repair and may require a combined intracranial extradural and intradural approach or a transcranial approach.10

Information on prophylactic antibiotics and vaccination is still evolving. Currently available evidence from randomized control trials does not support prophylactic antibiotic use in patients with basilar skull fracture with or without the evidence of CSF leakage.11 A meta‐analysis of 4 randomized controlled trials of patients with acute basilar skull fracture showed no significant difference between the antibiotic prophylaxis groups and control groups with respect to reduction of the frequency of meningitis, the need for surgical correction, meningitis‐related mortality, and all‐cause mortality.11 Direct invasion of the meninges by nasopharyngeal bacteria bypassing the circulating serum antibodies may limit the potential effectiveness of vaccination in preventing RBM.12 However, vaccination is generally recommended in patients with complement or immunoglobulin deficiency or after splenectomy.4

Recurrent bacterial meningitis (RBM), particularly when caused by Streptococcus pneumoniae, warrants an aggressive and thorough evaluation to exclude transdural communication. We present an unusual case of RBM as a late manifestation of a traumatic head injury sustained 10 years prior and describe presentation, etiology, diagnosis, and treatment options for RBM.

Case Report

A middle‐aged woman with type 2 diabetes mellitus, hypertension, and a prior history of S. pneumoniae meningitis 1 year earlier, presented to an outside hospital with complaints of fever, headache, and change in mental status. Materials for basic laboratory tests and blood cultures were drawn in the Emergency Department; these showed diabetic ketoacidosis. Computed tomography (CT) scan of the head was negative and a lumbar puncture (LP) was attempted, but was unsuccessful. The patient was started on intravenous insulin drip, vancomycin, and ceftriaxone and was transported to our facility via Life‐Flight. She also developed acute respiratory failure requiring mechanical ventilation.

After arrival, the patient had a normal repeat CT scan of her head and a successful LP. Cerebrospinal fluid (CSF) revealed 9064 white blood cells (WBCs)/mm³ with 77% neutrophils and 9% lymphocytes, protein concentration of 275 mg/dL, and glucose of 93 mg/dL. CSF culture and Gram stain were negative, while 1 blood culture drawn at the outside hospital grew penicillin‐resistant S. pneumoniae (MIC 2 g/mL). WBC count was 9660/mm³ with 45% band forms. Bacterial meningitis was confirmed and the patient was continued on intravenous antibiotics and insulin drip. Additional laboratory studies revealed normal complement levels and a negative human immunodeficiency virus (HIV) 1 and HIV 2 antibody screen. The patient was extubated in 48 hours. and was treated with a total of 2 weeks of ceftriaxone and vancomycin for penicillin‐resistant S. pneumoniae meningitis.

The patient had an uneventful full recovery and was discharged from the hospital with neurosurgery follow‐up. The neurosurgeon ordered a CT scan of the facial bones, which revealed an irregular calcification in the right frontal sinus adjacent to the cribriform plate and thinning of the posterior wall of the sinus. Upon requestioning at a subsequent neurosurgical appointment, the patient recalled being an unrestrained passenger and striking her head against the windshield in a motor vehicle accident (MVA) approximately 10 years ago. Ever since the MVA, she noticed intermittent postnasal discharge while recumbent. However, she never sought a medical opinion and denied complaints of anterior rhinorrhea.

A CT cisternography confirmed the presence of CSF leakage with contrast accumulation via a defect in the right paramedian cribriform plate. Contrast opacification was seen in the fovea ethmoidalis extending into the right frontal sinus (Figure 1). The patient subsequently underwent transnasal endoscopic CSF leak repair (Figure 2). The postoperative cisternogram did not reveal the transdural communication. However a follow‐up cisternogram performed 3 months later demonstrated a recurrent CSF leak.

Figure 1

Figure 2

The patient was rehospitalized with grand‐mal seizures and a third episode of S. pneumoniae meningitis, this time with a penicillin‐sensitive strain. She was treated with a 2‐week course of ceftriaxone and also received heptavalent pneumococcal vaccine to supplement the 23‐valent pneumococcal vaccine. Two weeks after the hospital discharge, the patient underwent successful bifrontal transcranial repair. Currently, she has been disease‐free for 3 months and is followed closely by neurosurgery as an outpatient.

Discussion

After immune deficiency is ruled out, it is essential to evaluate for transdural communication between the subarachnoid space and the base of the skull resulting in a CSF leak as a cause for RBM. Meningitis secondary to a CSF leak is most commonly caused by S. pneumoniae, followed by Neisseria meningitidis and Haemophilus influenzae.1 Complement and immunoglobulin subclass defects may also predispose to RBM.2, 3

A recent case series by Adriani et al.4 suggested that as many as 77% of patients with RBM have an identifiable risk factor such as a remote head injury or CSF leakage. CSF rhinorrhea is most often secondary to trauma, occurring in approximately 1% to 3% of all blunt head injuries.2 Accidental falls, MVAs, altercations, and gunshot wounds are also commonly responsible.3 Nontraumatic CSF leaks are very rare but may be secondary to spontaneous, congenital, or iatrogenic etiologies.1, 3 Spontaneous CSF leaks could also occur due to violent sneezing or coughing.1, 3 Congenital defects include weakened preformed pathways, failure of germ layer closures, and bone imperfections.1, 3 Infrequently, CSF leak can be a complication of intracranial, otologic, nasal, or paranasal sinus surgeries.1, 3 Other rarer etiologies include intracranial tumors and hydrocephalus.1, 3

Bacterial meningitis due to traumatic CSF leak can present within 24 hours to as long as several decades after the development of the leak.2, 3 Along with the classic symptoms and signs of meningitis, including fever, headache, neck stiffness, change in sensorium, seizures, and vomiting, patients may also present with CSF rhinorrhea, CSF otorrhea, hearing impairment, or cranial injury residua.3, 5 It is important to note that CSF rhinorrhea and otorrhea are not always present in cases of chronic, posttraumatic CSF leaks.

The visualization of a fracture or bony dehiscence is very difficult but critical for identification and surgical repair. Frontal and ethmoid sinuses and cribriform plate are common fracture sites.1, 3, 5 CSF leakage may be from the anterior, middle, or posterior compartments, eventually ending in the nasal cavity.1, 3, 5 Various imaging modalities, including contrast cisternogram, high‐resolution CT, fluorescein nasal endoscopy, and magnetic resonance imaging (MRI) have been advocated for diagnosing the source of CSF leak with variable sensitivity and specificity.6 High‐resolution CT helps in identifying surgical anatomy and bony defects whereas contrast cisternography is confirmatory when the CSF leak is active.1, 6 Protein electrophoresis demonstrating 2 electrophoretically separate transferrin bands confirms CSF.7

In patients with persistent CSF rhinorrhea, there is a 19% overall risk of meningitis with an annual incidence of 0.3 meningitis episodes per year.8 The risk of meningitis is the greatest in the first year following the onset of a CSF leak.8 Generally, patients with posttraumatic CSF leak lasting more than 7 to 10 days need surgical repair to decrease their risk of bacterial meningitis.1, 3, 5 Endoscopic surgical correction with a success rate of 90% is an effective treatment for CSF leak and involves placement of a temporary lumbar drain in addition to endonasal duraplasty performed with the aid of microscope and/or nasoscope.9 Complicated anterior cranial base fractures are not as amenable to endoscopic repair and may require a combined intracranial extradural and intradural approach or a transcranial approach.10

Information on prophylactic antibiotics and vaccination is still evolving. Currently available evidence from randomized control trials does not support prophylactic antibiotic use in patients with basilar skull fracture with or without the evidence of CSF leakage.11 A meta‐analysis of 4 randomized controlled trials of patients with acute basilar skull fracture showed no significant difference between the antibiotic prophylaxis groups and control groups with respect to reduction of the frequency of meningitis, the need for surgical correction, meningitis‐related mortality, and all‐cause mortality.11 Direct invasion of the meninges by nasopharyngeal bacteria bypassing the circulating serum antibodies may limit the potential effectiveness of vaccination in preventing RBM.12 However, vaccination is generally recommended in patients with complement or immunoglobulin deficiency or after splenectomy.4

Recurrent bacterial meningitis (RBM), particularly when caused by Streptococcus pneumoniae, warrants an aggressive and thorough evaluation to exclude transdural communication. We present an unusual case of RBM as a late manifestation of a traumatic head injury sustained 10 years prior and describe presentation, etiology, diagnosis, and treatment options for RBM.

Case Report

A middle‐aged woman with type 2 diabetes mellitus, hypertension, and a prior history of S. pneumoniae meningitis 1 year earlier, presented to an outside hospital with complaints of fever, headache, and change in mental status. Materials for basic laboratory tests and blood cultures were drawn in the Emergency Department; these showed diabetic ketoacidosis. Computed tomography (CT) scan of the head was negative and a lumbar puncture (LP) was attempted, but was unsuccessful. The patient was started on intravenous insulin drip, vancomycin, and ceftriaxone and was transported to our facility via Life‐Flight. She also developed acute respiratory failure requiring mechanical ventilation.

After arrival, the patient had a normal repeat CT scan of her head and a successful LP. Cerebrospinal fluid (CSF) revealed 9064 white blood cells (WBCs)/mm³ with 77% neutrophils and 9% lymphocytes, protein concentration of 275 mg/dL, and glucose of 93 mg/dL. CSF culture and Gram stain were negative, while 1 blood culture drawn at the outside hospital grew penicillin‐resistant S. pneumoniae (MIC 2 g/mL). WBC count was 9660/mm³ with 45% band forms. Bacterial meningitis was confirmed and the patient was continued on intravenous antibiotics and insulin drip. Additional laboratory studies revealed normal complement levels and a negative human immunodeficiency virus (HIV) 1 and HIV 2 antibody screen. The patient was extubated in 48 hours. and was treated with a total of 2 weeks of ceftriaxone and vancomycin for penicillin‐resistant S. pneumoniae meningitis.

The patient had an uneventful full recovery and was discharged from the hospital with neurosurgery follow‐up. The neurosurgeon ordered a CT scan of the facial bones, which revealed an irregular calcification in the right frontal sinus adjacent to the cribriform plate and thinning of the posterior wall of the sinus. Upon requestioning at a subsequent neurosurgical appointment, the patient recalled being an unrestrained passenger and striking her head against the windshield in a motor vehicle accident (MVA) approximately 10 years ago. Ever since the MVA, she noticed intermittent postnasal discharge while recumbent. However, she never sought a medical opinion and denied complaints of anterior rhinorrhea.

A CT cisternography confirmed the presence of CSF leakage with contrast accumulation via a defect in the right paramedian cribriform plate. Contrast opacification was seen in the fovea ethmoidalis extending into the right frontal sinus (Figure 1). The patient subsequently underwent transnasal endoscopic CSF leak repair (Figure 2). The postoperative cisternogram did not reveal the transdural communication. However a follow‐up cisternogram performed 3 months later demonstrated a recurrent CSF leak.

Figure 1

Figure 2

The patient was rehospitalized with grand‐mal seizures and a third episode of S. pneumoniae meningitis, this time with a penicillin‐sensitive strain. She was treated with a 2‐week course of ceftriaxone and also received heptavalent pneumococcal vaccine to supplement the 23‐valent pneumococcal vaccine. Two weeks after the hospital discharge, the patient underwent successful bifrontal transcranial repair. Currently, she has been disease‐free for 3 months and is followed closely by neurosurgery as an outpatient.

Discussion

After immune deficiency is ruled out, it is essential to evaluate for transdural communication between the subarachnoid space and the base of the skull resulting in a CSF leak as a cause for RBM. Meningitis secondary to a CSF leak is most commonly caused by S. pneumoniae, followed by Neisseria meningitidis and Haemophilus influenzae.1 Complement and immunoglobulin subclass defects may also predispose to RBM.2, 3

A recent case series by Adriani et al.4 suggested that as many as 77% of patients with RBM have an identifiable risk factor such as a remote head injury or CSF leakage. CSF rhinorrhea is most often secondary to trauma, occurring in approximately 1% to 3% of all blunt head injuries.2 Accidental falls, MVAs, altercations, and gunshot wounds are also commonly responsible.3 Nontraumatic CSF leaks are very rare but may be secondary to spontaneous, congenital, or iatrogenic etiologies.1, 3 Spontaneous CSF leaks could also occur due to violent sneezing or coughing.1, 3 Congenital defects include weakened preformed pathways, failure of germ layer closures, and bone imperfections.1, 3 Infrequently, CSF leak can be a complication of intracranial, otologic, nasal, or paranasal sinus surgeries.1, 3 Other rarer etiologies include intracranial tumors and hydrocephalus.1, 3

Bacterial meningitis due to traumatic CSF leak can present within 24 hours to as long as several decades after the development of the leak.2, 3 Along with the classic symptoms and signs of meningitis, including fever, headache, neck stiffness, change in sensorium, seizures, and vomiting, patients may also present with CSF rhinorrhea, CSF otorrhea, hearing impairment, or cranial injury residua.3, 5 It is important to note that CSF rhinorrhea and otorrhea are not always present in cases of chronic, posttraumatic CSF leaks.

The visualization of a fracture or bony dehiscence is very difficult but critical for identification and surgical repair. Frontal and ethmoid sinuses and cribriform plate are common fracture sites.1, 3, 5 CSF leakage may be from the anterior, middle, or posterior compartments, eventually ending in the nasal cavity.1, 3, 5 Various imaging modalities, including contrast cisternogram, high‐resolution CT, fluorescein nasal endoscopy, and magnetic resonance imaging (MRI) have been advocated for diagnosing the source of CSF leak with variable sensitivity and specificity.6 High‐resolution CT helps in identifying surgical anatomy and bony defects whereas contrast cisternography is confirmatory when the CSF leak is active.1, 6 Protein electrophoresis demonstrating 2 electrophoretically separate transferrin bands confirms CSF.7

In patients with persistent CSF rhinorrhea, there is a 19% overall risk of meningitis with an annual incidence of 0.3 meningitis episodes per year.8 The risk of meningitis is the greatest in the first year following the onset of a CSF leak.8 Generally, patients with posttraumatic CSF leak lasting more than 7 to 10 days need surgical repair to decrease their risk of bacterial meningitis.1, 3, 5 Endoscopic surgical correction with a success rate of 90% is an effective treatment for CSF leak and involves placement of a temporary lumbar drain in addition to endonasal duraplasty performed with the aid of microscope and/or nasoscope.9 Complicated anterior cranial base fractures are not as amenable to endoscopic repair and may require a combined intracranial extradural and intradural approach or a transcranial approach.10

Information on prophylactic antibiotics and vaccination is still evolving. Currently available evidence from randomized control trials does not support prophylactic antibiotic use in patients with basilar skull fracture with or without the evidence of CSF leakage.11 A meta‐analysis of 4 randomized controlled trials of patients with acute basilar skull fracture showed no significant difference between the antibiotic prophylaxis groups and control groups with respect to reduction of the frequency of meningitis, the need for surgical correction, meningitis‐related mortality, and all‐cause mortality.11 Direct invasion of the meninges by nasopharyngeal bacteria bypassing the circulating serum antibodies may limit the potential effectiveness of vaccination in preventing RBM.12 However, vaccination is generally recommended in patients with complement or immunoglobulin deficiency or after splenectomy.4

A previously healthy 25‐year‐old Guatemalan man presented to the emergency department with 1 day of fever, nausea, vomiting, and right lower quadrant abdominal pain. A computed tomography (CT) scan revealed acute appendicitis. The patient underwent an uncomplicated laparoscopic appendectomy and was discharged in stable condition after 48 hours.

Five days after the operation he returned to the emergency department with abdominal pain, nausea, vomiting, and lightheadedness. He was tachycardic, and his hemoglobin was 9.5 g/dL (normal, 13.3‐17.7 g/dL), decreased from 14.4 g/dL prior to his appendectomy. A CT scan showed intraperitoneal blood with active extravasation of contrast at the site of the appendectomy.

Additional laboratory testing revealed an activated partial thromboplastin time (aPTT) of 52 seconds (normal, 37 seconds) and protime (also prothrombin time [PT]) of 14 seconds (normal, 14.1 seconds). The platelet count was 449,000/L (normal, 150‐400,000/L) and the fibrinogen level was 337 mg/dL (normal, 170‐440 mg/dL). Crystalloid and packed red blood cells were administered. Since further laboratory evaluation of the prolonged aPTT was not immediately available, the patient was empirically treated with fresh frozen plasma (FFP), cryoprecipitate, and Factor VIII/von Willebrand factor concentrate. At laparotomy, bleeding was observed at the previous operative site, and 2 L of intraperitoneal blood was evacuated.

The next morning, Factor VIII and Factor IX (FIX) activities and the ristocetin cofactor study performed on specimens obtained immediately prior to the second operation were normal, but the FIX activity was 5% of normal. The diagnosis of FXI deficiency was made and 2 to 3 units of FFP (the amount necessary to maintain the patient's measured FXI activity near 20% of normal) were transfused daily. Nine days of FFP infusions were required to achieve complete wound hemostasis. The patient had no further bleeding episodes after discharge.

Upon further interviewing, the patient revealed that 2 months prior he sustained a small laceration on his arm that bled for a long time and that his brother had experienced prolonged bleeding after a dental extraction.

Commentary

Routine performance of preprocedural laboratory testing, and complete reliance on the results as a means of excluding a propensity to bleeding, may not only lead to excessive testing and delayed procedures, but also provides false reassurance because normal routine laboratory studies cannot be used to exclude some bleeding disorders (Table 1).

Most studies evaluating routine laboratory testing of hemostatic variables prior to invasive procedures come from patients undergoing elective general surgery. A 1988 study concluded that there is no benefit in the routine preoperative use of the PT, aPTT, platelet count, and bleeding time in the absence of clinical evidence of a hemostatic defect, as assessed by a patient questionnaire and a thorough physical examination.¹ A subsequent European, prospective, multicenter study confirmed that abnormalities of preoperative laboratory screening in the absence of a history of bleeding or clinical abnormality were not associated with worse surgical morbidity or mortality, compared to patients with normal screening laboratory studies.² A recent systematic review has also confirmed the poor positive predictive value of screening tests when used in isolation, and recommended a history‐based and physical exam‐based approach.³ Questionnaires have been shown to be particularly important tools for eliciting clinically significant bleeding disorders that may require revision of the surgical plan.^1,4

FXI is a serine protease whose activity is crucial for robust fibrin clot formation and inhibition of fibrinolysis at sites of vascular injury.⁵ FXI deficiency is an autosomal recessive disorder with an incidence of 1 per 1,000,000 in the general population, with a significantly higher incidence in the Ashkenazi Jewish population. While the risk of spontaneous hemorrhage is typically low, life‐threatening bleeding may occur after surgery or trauma. The severity of the measured FXI level deficiency does not always correlate with risk of bleeding. Periprocedural prophylaxis and treatment of bleeding aim to replace FXI to the low‐normal range by administering FXI concentrate, (not available in the United States) or FFP. Antifibrinolytic agents such as tranexamic acid or ϵ‐aminocaproic acid may be used adjunctively in cases of mucosal bleeding.⁵

In this case, preoperative screening, either using a questionnaire or careful history‐taking, would have identified the patient's personal and family history of bleeding and prompted appropriate preoperative coagulation testing, which could have exposed the hemostatic defect, allowing for modification of the perioperative medical plan.

In summary, preoperative bleeding evaluations should be performed routinely and should begin with a careful history (use of a questionnaire may be considered) and physical examination. Excessive bleeding after prior surgery, trauma, dental extractions, parturition, or circumcision; bleeding tendency in family members; current use of medications that may increase bleeding risk (such as anticoagulants or aspirin); and physical signs associated with bleeding should be assessed. If clinical details fail to expose a potential bleeding disorder, it is safe and cost‐effective¹ to proceed with surgery without performing additional laboratory testing. In contrast, any abnormality on the clinical assessment should trigger preoperative laboratory analysis of basic hemostatic parameters, which may prompt further testing or hematology consultation.

A previously healthy 25‐year‐old Guatemalan man presented to the emergency department with 1 day of fever, nausea, vomiting, and right lower quadrant abdominal pain. A computed tomography (CT) scan revealed acute appendicitis. The patient underwent an uncomplicated laparoscopic appendectomy and was discharged in stable condition after 48 hours.

Five days after the operation he returned to the emergency department with abdominal pain, nausea, vomiting, and lightheadedness. He was tachycardic, and his hemoglobin was 9.5 g/dL (normal, 13.3‐17.7 g/dL), decreased from 14.4 g/dL prior to his appendectomy. A CT scan showed intraperitoneal blood with active extravasation of contrast at the site of the appendectomy.

Additional laboratory testing revealed an activated partial thromboplastin time (aPTT) of 52 seconds (normal, 37 seconds) and protime (also prothrombin time [PT]) of 14 seconds (normal, 14.1 seconds). The platelet count was 449,000/L (normal, 150‐400,000/L) and the fibrinogen level was 337 mg/dL (normal, 170‐440 mg/dL). Crystalloid and packed red blood cells were administered. Since further laboratory evaluation of the prolonged aPTT was not immediately available, the patient was empirically treated with fresh frozen plasma (FFP), cryoprecipitate, and Factor VIII/von Willebrand factor concentrate. At laparotomy, bleeding was observed at the previous operative site, and 2 L of intraperitoneal blood was evacuated.

The next morning, Factor VIII and Factor IX (FIX) activities and the ristocetin cofactor study performed on specimens obtained immediately prior to the second operation were normal, but the FIX activity was 5% of normal. The diagnosis of FXI deficiency was made and 2 to 3 units of FFP (the amount necessary to maintain the patient's measured FXI activity near 20% of normal) were transfused daily. Nine days of FFP infusions were required to achieve complete wound hemostasis. The patient had no further bleeding episodes after discharge.

Upon further interviewing, the patient revealed that 2 months prior he sustained a small laceration on his arm that bled for a long time and that his brother had experienced prolonged bleeding after a dental extraction.

Commentary

Routine performance of preprocedural laboratory testing, and complete reliance on the results as a means of excluding a propensity to bleeding, may not only lead to excessive testing and delayed procedures, but also provides false reassurance because normal routine laboratory studies cannot be used to exclude some bleeding disorders (Table 1).

Most studies evaluating routine laboratory testing of hemostatic variables prior to invasive procedures come from patients undergoing elective general surgery. A 1988 study concluded that there is no benefit in the routine preoperative use of the PT, aPTT, platelet count, and bleeding time in the absence of clinical evidence of a hemostatic defect, as assessed by a patient questionnaire and a thorough physical examination.¹ A subsequent European, prospective, multicenter study confirmed that abnormalities of preoperative laboratory screening in the absence of a history of bleeding or clinical abnormality were not associated with worse surgical morbidity or mortality, compared to patients with normal screening laboratory studies.² A recent systematic review has also confirmed the poor positive predictive value of screening tests when used in isolation, and recommended a history‐based and physical exam‐based approach.³ Questionnaires have been shown to be particularly important tools for eliciting clinically significant bleeding disorders that may require revision of the surgical plan.^1,4

FXI is a serine protease whose activity is crucial for robust fibrin clot formation and inhibition of fibrinolysis at sites of vascular injury.⁵ FXI deficiency is an autosomal recessive disorder with an incidence of 1 per 1,000,000 in the general population, with a significantly higher incidence in the Ashkenazi Jewish population. While the risk of spontaneous hemorrhage is typically low, life‐threatening bleeding may occur after surgery or trauma. The severity of the measured FXI level deficiency does not always correlate with risk of bleeding. Periprocedural prophylaxis and treatment of bleeding aim to replace FXI to the low‐normal range by administering FXI concentrate, (not available in the United States) or FFP. Antifibrinolytic agents such as tranexamic acid or ϵ‐aminocaproic acid may be used adjunctively in cases of mucosal bleeding.⁵

In this case, preoperative screening, either using a questionnaire or careful history‐taking, would have identified the patient's personal and family history of bleeding and prompted appropriate preoperative coagulation testing, which could have exposed the hemostatic defect, allowing for modification of the perioperative medical plan.

In summary, preoperative bleeding evaluations should be performed routinely and should begin with a careful history (use of a questionnaire may be considered) and physical examination. Excessive bleeding after prior surgery, trauma, dental extractions, parturition, or circumcision; bleeding tendency in family members; current use of medications that may increase bleeding risk (such as anticoagulants or aspirin); and physical signs associated with bleeding should be assessed. If clinical details fail to expose a potential bleeding disorder, it is safe and cost‐effective¹ to proceed with surgery without performing additional laboratory testing. In contrast, any abnormality on the clinical assessment should trigger preoperative laboratory analysis of basic hemostatic parameters, which may prompt further testing or hematology consultation.

A previously healthy 25‐year‐old Guatemalan man presented to the emergency department with 1 day of fever, nausea, vomiting, and right lower quadrant abdominal pain. A computed tomography (CT) scan revealed acute appendicitis. The patient underwent an uncomplicated laparoscopic appendectomy and was discharged in stable condition after 48 hours.

Five days after the operation he returned to the emergency department with abdominal pain, nausea, vomiting, and lightheadedness. He was tachycardic, and his hemoglobin was 9.5 g/dL (normal, 13.3‐17.7 g/dL), decreased from 14.4 g/dL prior to his appendectomy. A CT scan showed intraperitoneal blood with active extravasation of contrast at the site of the appendectomy.

Additional laboratory testing revealed an activated partial thromboplastin time (aPTT) of 52 seconds (normal, 37 seconds) and protime (also prothrombin time [PT]) of 14 seconds (normal, 14.1 seconds). The platelet count was 449,000/L (normal, 150‐400,000/L) and the fibrinogen level was 337 mg/dL (normal, 170‐440 mg/dL). Crystalloid and packed red blood cells were administered. Since further laboratory evaluation of the prolonged aPTT was not immediately available, the patient was empirically treated with fresh frozen plasma (FFP), cryoprecipitate, and Factor VIII/von Willebrand factor concentrate. At laparotomy, bleeding was observed at the previous operative site, and 2 L of intraperitoneal blood was evacuated.

The next morning, Factor VIII and Factor IX (FIX) activities and the ristocetin cofactor study performed on specimens obtained immediately prior to the second operation were normal, but the FIX activity was 5% of normal. The diagnosis of FXI deficiency was made and 2 to 3 units of FFP (the amount necessary to maintain the patient's measured FXI activity near 20% of normal) were transfused daily. Nine days of FFP infusions were required to achieve complete wound hemostasis. The patient had no further bleeding episodes after discharge.

Upon further interviewing, the patient revealed that 2 months prior he sustained a small laceration on his arm that bled for a long time and that his brother had experienced prolonged bleeding after a dental extraction.

Commentary

Routine performance of preprocedural laboratory testing, and complete reliance on the results as a means of excluding a propensity to bleeding, may not only lead to excessive testing and delayed procedures, but also provides false reassurance because normal routine laboratory studies cannot be used to exclude some bleeding disorders (Table 1).

Most studies evaluating routine laboratory testing of hemostatic variables prior to invasive procedures come from patients undergoing elective general surgery. A 1988 study concluded that there is no benefit in the routine preoperative use of the PT, aPTT, platelet count, and bleeding time in the absence of clinical evidence of a hemostatic defect, as assessed by a patient questionnaire and a thorough physical examination.¹ A subsequent European, prospective, multicenter study confirmed that abnormalities of preoperative laboratory screening in the absence of a history of bleeding or clinical abnormality were not associated with worse surgical morbidity or mortality, compared to patients with normal screening laboratory studies.² A recent systematic review has also confirmed the poor positive predictive value of screening tests when used in isolation, and recommended a history‐based and physical exam‐based approach.³ Questionnaires have been shown to be particularly important tools for eliciting clinically significant bleeding disorders that may require revision of the surgical plan.^1,4

FXI is a serine protease whose activity is crucial for robust fibrin clot formation and inhibition of fibrinolysis at sites of vascular injury.⁵ FXI deficiency is an autosomal recessive disorder with an incidence of 1 per 1,000,000 in the general population, with a significantly higher incidence in the Ashkenazi Jewish population. While the risk of spontaneous hemorrhage is typically low, life‐threatening bleeding may occur after surgery or trauma. The severity of the measured FXI level deficiency does not always correlate with risk of bleeding. Periprocedural prophylaxis and treatment of bleeding aim to replace FXI to the low‐normal range by administering FXI concentrate, (not available in the United States) or FFP. Antifibrinolytic agents such as tranexamic acid or ϵ‐aminocaproic acid may be used adjunctively in cases of mucosal bleeding.⁵

In this case, preoperative screening, either using a questionnaire or careful history‐taking, would have identified the patient's personal and family history of bleeding and prompted appropriate preoperative coagulation testing, which could have exposed the hemostatic defect, allowing for modification of the perioperative medical plan.

In summary, preoperative bleeding evaluations should be performed routinely and should begin with a careful history (use of a questionnaire may be considered) and physical examination. Excessive bleeding after prior surgery, trauma, dental extractions, parturition, or circumcision; bleeding tendency in family members; current use of medications that may increase bleeding risk (such as anticoagulants or aspirin); and physical signs associated with bleeding should be assessed. If clinical details fail to expose a potential bleeding disorder, it is safe and cost‐effective¹ to proceed with surgery without performing additional laboratory testing. In contrast, any abnormality on the clinical assessment should trigger preoperative laboratory analysis of basic hemostatic parameters, which may prompt further testing or hematology consultation.

A 56‐year‐old male presented to the emergency department with a 2‐week history of increasing abdominal girth, nausea, vomiting, and lower extremity edema. His girlfriend had also noted a yellow tinge to his skin and eyes. His past medical history was significant for bipolar disorder, alcohol‐related seizures, and pneumonia. He had no allergies and denied medications prior to admission. Family history was negative for liver disease and social history was notable for ongoing tobacco use and alcohol dependence. He was afebrile with stable vital signs. Physical examination demonstrated an alert gentleman whose answers to questions required occasional factual correction by his partner. His abdomen was distended and nontender with prominent vasculature and shifting dullness. Lower extremity edema was symmetric and bilateral, rated as 2+. Scattered spider angiomata and a fine bilateral hand tremor without asterixis were also noted. Initial laboratory data demonstrated a white blood cell count of 13,900/L, hematocrit 37%, and platelet count 176,000/L. His sodium was 130 mg/dL, blood urea nitrogen (BUN) 1 mg/dL, and creatinine 0.7 mg/dL. International normalized ratio (INR) was 1.8, aspartate aminotransferase (AST) was 117 U/L, alanine aminotransferase (ALT) 33 U/L, alkaline phosphatase 191 U/L, total bilirubin 9.2 mg/dL, total protein 7.0 g/dL, and albumin 1.9 g/dL. Abdominal ultrasound revealed a diffusely hyperechoic liver with a large amount of ascites.

The patient was admitted with the diagnoses of presumed alcoholic hepatitis and end‐stage liver disease. Model for End‐Stage Liver Disease (MELD) score was 21 and discriminant function 16.8. Paracentesis demonstrated a serum‐ascites albumin gradient of >1.1 and no evidence of spontaneous bacterial peritonitis. Diuresis was initiated. He was placed on unfractionated heparin at a dose of 5000 units every 8 hours for deep venous thrombosis (DVT) prophylaxis. By hospital day 3, the patient's laboratory values had improved, yet his stay was prolonged by alcohol withdrawal requiring benzodiazepines, altered mental status presumed secondary to hepatic encephalopathy, acute renal failure, aspiration pneumonia, and persistent unexplained leukocytosis. He required medical restraints during this time given confusion and propensity to ambulate without assistance, yet sustained no falls or other known trauma in care delivered during this time.

Between days 14 and 17, the patient's hematocrit fell from 36% to 30%; vital signs remained stable. He underwent an uncomplicated, ultrasound‐guided therapeutic paracentesis, which yielded 1.4 L of straw‐colored fluid on the afternoon of day 17; the procedure was attempted only on the right side. On the morning of day 18, the patient's blood pressure dropped to 78/55 mmHg with a pulse of 123 beats per minute; he became pale and unresponsive. Physical examination was notable for somnolence and a tender, warm left flank mass, contralateral to his paracentesis site. No flank or periumbilical ecchymoses were identified. Complete blood count demonstrated a white blood count (WBC) of 22,970/L, hematocrit 16%, and platelet count 104,000/L. INR was 2.0, unchanged from the last check on day 10. Partial thromboplastin time was 41 seconds and fibrinogen was 293 mg/dL (normal 150‐400 mg/dL). Peripheral blood smear was negative for red cell fragments. Blood chemistries revealed a sodium of 134 mg/dL, bicarbonate 20 mEq/L, anion gap 7, BUN 24 mg/dL, and creatinine 1.6 mg/dL (up from 1.0 mg/dL the previous day). His venous lactate level was 4.6 mmol/L and arterial blood gas sampling on room air demonstrated a pH of 7.35, partial pressure of carbon dioxide (pCO₂) 29 mmHg, partial pressure of oxygen (pCO₂) 54 mmHg, and bicarbonate 15 mEq/L. A femoral introducer was placed for volume resuscitation and the patient was urgently transfused with packed red blood cells (PRBCs) and fresh‐frozen plasma (FFP) to correct his coagulopathy. Computed tomography of the abdomen revealed a large left retroperitoneal hematoma measuring 15 15 22 cm³ (Figure 1). Despite transfusion, his hematocrit continued to fall. Urgent angiography was performed, upon which he was found to have active bleeding from the left L3‐L5 lumbar arteries. These were successfully embolized. He required PRBCs and FFP transfusion only once following this procedure. Given a transient decrease in his urine output, his bladder pressures were followed closely for evidence of abdominal compartment syndrome, which did not develop. He was transferred from the intensive care unit (ICU) to the floor on day 20, where his physical exam and hematocrit remained stable and his delirium slowly cleared. He was ultimately discharged to a skilled nursing facility on day 33.

Figure 1

Discussion

Spontaneous retroperitoneal hematoma is a well‐recognized entity that may present with the classic triad of abdominal or groin pain, palpable abdominal or flank mass, and shock or lower extremity motor or sensory changes due to femoral nerve compression.1 Although classically described as skin findings associated with retroperitoneal hemorrhage, Cullen and Grey‐Turner signs are relatively late findings that may not develop in all patients.

Retroperitoneal hemorrhage is well‐recognized as a result of iatrogenic anticoagulation,1 but has been reported less commonly as a result of coagulopathy related to cirrhosis. Di Bisceglie and Richart2 describe 2 patients with MELD scores of 29 and 25, respectively, who developed spontaneous retroperitoneal and rectus muscle hemorrhage. Both had evidence of associated disseminated intravascular coagulation (DIC) and died. Even less common is spontaneous lumbar artery rupture, occurring rarely in the absence of trauma or instrumentation. One reported bleed developed in the context of systemic anticoagulation for a mechanical valve.3 Halak et al.4 relate a case in which the only known risk factor was chronic renal disease. Hama et al.5 describe a patient with a history of alcoholic liver cirrhosis and INR of 2.3 whose lumbar artery rupture was successfully managed with transcatheter arterial embolization.

It is difficult to ascertain the effect of prophylactic anticoagulation in development of this particular hemorrhage. Retroperitoneal bleeding is a very rare complication of pharmacologic prophylaxis for DVT reported with both low‐molecular weight and unfractionated heparins.6 There may be additive risk of prophylaxis in a cirrhotic patient with baseline elevated INR and thrombocytopenia, particularly in the context of renal failure.

Options in the management of spontaneous retroperitoneal hematoma include transarterial embolization, percutaneous decompression, and open surgery. Nonoperative management of these bleeds when possible may be preferable in cirrhotic patients, as their baseline liver disease renders them higher‐risk candidates for surgery. There are no randomized trials comparing these approaches.1

In summary, we report the case of a 56‐year‐old man with end‐stage liver disease and associated coagulopathy without evidence of DIC who survived to discharge with intravascular management of a spontaneous retroperitoneal hemorrhage from the lumbar arteries. To our knowledge, this is the second reported case of spontaneous retroperitoneal hemorrhage in a cirrhotic in which the lumbar arteries were implicated and the first in which multiple arteries were found to be bleeding simultaneously. Any hospitalized patient who develops abdominal pain, flank pain, or hemodynamic instability in the context of coagulopathy, regardless of cause, warrants evaluation for retroperitoneal bleed. Appropriate early management includes immediate resuscitation, intensive monitoring, urgent imaging, and surgical and interventional radiology consultation in order to prevent a fatal outcome.

A 56‐year‐old male presented to the emergency department with a 2‐week history of increasing abdominal girth, nausea, vomiting, and lower extremity edema. His girlfriend had also noted a yellow tinge to his skin and eyes. His past medical history was significant for bipolar disorder, alcohol‐related seizures, and pneumonia. He had no allergies and denied medications prior to admission. Family history was negative for liver disease and social history was notable for ongoing tobacco use and alcohol dependence. He was afebrile with stable vital signs. Physical examination demonstrated an alert gentleman whose answers to questions required occasional factual correction by his partner. His abdomen was distended and nontender with prominent vasculature and shifting dullness. Lower extremity edema was symmetric and bilateral, rated as 2+. Scattered spider angiomata and a fine bilateral hand tremor without asterixis were also noted. Initial laboratory data demonstrated a white blood cell count of 13,900/L, hematocrit 37%, and platelet count 176,000/L. His sodium was 130 mg/dL, blood urea nitrogen (BUN) 1 mg/dL, and creatinine 0.7 mg/dL. International normalized ratio (INR) was 1.8, aspartate aminotransferase (AST) was 117 U/L, alanine aminotransferase (ALT) 33 U/L, alkaline phosphatase 191 U/L, total bilirubin 9.2 mg/dL, total protein 7.0 g/dL, and albumin 1.9 g/dL. Abdominal ultrasound revealed a diffusely hyperechoic liver with a large amount of ascites.

The patient was admitted with the diagnoses of presumed alcoholic hepatitis and end‐stage liver disease. Model for End‐Stage Liver Disease (MELD) score was 21 and discriminant function 16.8. Paracentesis demonstrated a serum‐ascites albumin gradient of >1.1 and no evidence of spontaneous bacterial peritonitis. Diuresis was initiated. He was placed on unfractionated heparin at a dose of 5000 units every 8 hours for deep venous thrombosis (DVT) prophylaxis. By hospital day 3, the patient's laboratory values had improved, yet his stay was prolonged by alcohol withdrawal requiring benzodiazepines, altered mental status presumed secondary to hepatic encephalopathy, acute renal failure, aspiration pneumonia, and persistent unexplained leukocytosis. He required medical restraints during this time given confusion and propensity to ambulate without assistance, yet sustained no falls or other known trauma in care delivered during this time.

Between days 14 and 17, the patient's hematocrit fell from 36% to 30%; vital signs remained stable. He underwent an uncomplicated, ultrasound‐guided therapeutic paracentesis, which yielded 1.4 L of straw‐colored fluid on the afternoon of day 17; the procedure was attempted only on the right side. On the morning of day 18, the patient's blood pressure dropped to 78/55 mmHg with a pulse of 123 beats per minute; he became pale and unresponsive. Physical examination was notable for somnolence and a tender, warm left flank mass, contralateral to his paracentesis site. No flank or periumbilical ecchymoses were identified. Complete blood count demonstrated a white blood count (WBC) of 22,970/L, hematocrit 16%, and platelet count 104,000/L. INR was 2.0, unchanged from the last check on day 10. Partial thromboplastin time was 41 seconds and fibrinogen was 293 mg/dL (normal 150‐400 mg/dL). Peripheral blood smear was negative for red cell fragments. Blood chemistries revealed a sodium of 134 mg/dL, bicarbonate 20 mEq/L, anion gap 7, BUN 24 mg/dL, and creatinine 1.6 mg/dL (up from 1.0 mg/dL the previous day). His venous lactate level was 4.6 mmol/L and arterial blood gas sampling on room air demonstrated a pH of 7.35, partial pressure of carbon dioxide (pCO₂) 29 mmHg, partial pressure of oxygen (pCO₂) 54 mmHg, and bicarbonate 15 mEq/L. A femoral introducer was placed for volume resuscitation and the patient was urgently transfused with packed red blood cells (PRBCs) and fresh‐frozen plasma (FFP) to correct his coagulopathy. Computed tomography of the abdomen revealed a large left retroperitoneal hematoma measuring 15 15 22 cm³ (Figure 1). Despite transfusion, his hematocrit continued to fall. Urgent angiography was performed, upon which he was found to have active bleeding from the left L3‐L5 lumbar arteries. These were successfully embolized. He required PRBCs and FFP transfusion only once following this procedure. Given a transient decrease in his urine output, his bladder pressures were followed closely for evidence of abdominal compartment syndrome, which did not develop. He was transferred from the intensive care unit (ICU) to the floor on day 20, where his physical exam and hematocrit remained stable and his delirium slowly cleared. He was ultimately discharged to a skilled nursing facility on day 33.

Figure 1

Discussion

Spontaneous retroperitoneal hematoma is a well‐recognized entity that may present with the classic triad of abdominal or groin pain, palpable abdominal or flank mass, and shock or lower extremity motor or sensory changes due to femoral nerve compression.1 Although classically described as skin findings associated with retroperitoneal hemorrhage, Cullen and Grey‐Turner signs are relatively late findings that may not develop in all patients.

Retroperitoneal hemorrhage is well‐recognized as a result of iatrogenic anticoagulation,1 but has been reported less commonly as a result of coagulopathy related to cirrhosis. Di Bisceglie and Richart2 describe 2 patients with MELD scores of 29 and 25, respectively, who developed spontaneous retroperitoneal and rectus muscle hemorrhage. Both had evidence of associated disseminated intravascular coagulation (DIC) and died. Even less common is spontaneous lumbar artery rupture, occurring rarely in the absence of trauma or instrumentation. One reported bleed developed in the context of systemic anticoagulation for a mechanical valve.3 Halak et al.4 relate a case in which the only known risk factor was chronic renal disease. Hama et al.5 describe a patient with a history of alcoholic liver cirrhosis and INR of 2.3 whose lumbar artery rupture was successfully managed with transcatheter arterial embolization.

It is difficult to ascertain the effect of prophylactic anticoagulation in development of this particular hemorrhage. Retroperitoneal bleeding is a very rare complication of pharmacologic prophylaxis for DVT reported with both low‐molecular weight and unfractionated heparins.6 There may be additive risk of prophylaxis in a cirrhotic patient with baseline elevated INR and thrombocytopenia, particularly in the context of renal failure.

Options in the management of spontaneous retroperitoneal hematoma include transarterial embolization, percutaneous decompression, and open surgery. Nonoperative management of these bleeds when possible may be preferable in cirrhotic patients, as their baseline liver disease renders them higher‐risk candidates for surgery. There are no randomized trials comparing these approaches.1

In summary, we report the case of a 56‐year‐old man with end‐stage liver disease and associated coagulopathy without evidence of DIC who survived to discharge with intravascular management of a spontaneous retroperitoneal hemorrhage from the lumbar arteries. To our knowledge, this is the second reported case of spontaneous retroperitoneal hemorrhage in a cirrhotic in which the lumbar arteries were implicated and the first in which multiple arteries were found to be bleeding simultaneously. Any hospitalized patient who develops abdominal pain, flank pain, or hemodynamic instability in the context of coagulopathy, regardless of cause, warrants evaluation for retroperitoneal bleed. Appropriate early management includes immediate resuscitation, intensive monitoring, urgent imaging, and surgical and interventional radiology consultation in order to prevent a fatal outcome.

A 56‐year‐old male presented to the emergency department with a 2‐week history of increasing abdominal girth, nausea, vomiting, and lower extremity edema. His girlfriend had also noted a yellow tinge to his skin and eyes. His past medical history was significant for bipolar disorder, alcohol‐related seizures, and pneumonia. He had no allergies and denied medications prior to admission. Family history was negative for liver disease and social history was notable for ongoing tobacco use and alcohol dependence. He was afebrile with stable vital signs. Physical examination demonstrated an alert gentleman whose answers to questions required occasional factual correction by his partner. His abdomen was distended and nontender with prominent vasculature and shifting dullness. Lower extremity edema was symmetric and bilateral, rated as 2+. Scattered spider angiomata and a fine bilateral hand tremor without asterixis were also noted. Initial laboratory data demonstrated a white blood cell count of 13,900/L, hematocrit 37%, and platelet count 176,000/L. His sodium was 130 mg/dL, blood urea nitrogen (BUN) 1 mg/dL, and creatinine 0.7 mg/dL. International normalized ratio (INR) was 1.8, aspartate aminotransferase (AST) was 117 U/L, alanine aminotransferase (ALT) 33 U/L, alkaline phosphatase 191 U/L, total bilirubin 9.2 mg/dL, total protein 7.0 g/dL, and albumin 1.9 g/dL. Abdominal ultrasound revealed a diffusely hyperechoic liver with a large amount of ascites.

The patient was admitted with the diagnoses of presumed alcoholic hepatitis and end‐stage liver disease. Model for End‐Stage Liver Disease (MELD) score was 21 and discriminant function 16.8. Paracentesis demonstrated a serum‐ascites albumin gradient of >1.1 and no evidence of spontaneous bacterial peritonitis. Diuresis was initiated. He was placed on unfractionated heparin at a dose of 5000 units every 8 hours for deep venous thrombosis (DVT) prophylaxis. By hospital day 3, the patient's laboratory values had improved, yet his stay was prolonged by alcohol withdrawal requiring benzodiazepines, altered mental status presumed secondary to hepatic encephalopathy, acute renal failure, aspiration pneumonia, and persistent unexplained leukocytosis. He required medical restraints during this time given confusion and propensity to ambulate without assistance, yet sustained no falls or other known trauma in care delivered during this time.

Between days 14 and 17, the patient's hematocrit fell from 36% to 30%; vital signs remained stable. He underwent an uncomplicated, ultrasound‐guided therapeutic paracentesis, which yielded 1.4 L of straw‐colored fluid on the afternoon of day 17; the procedure was attempted only on the right side. On the morning of day 18, the patient's blood pressure dropped to 78/55 mmHg with a pulse of 123 beats per minute; he became pale and unresponsive. Physical examination was notable for somnolence and a tender, warm left flank mass, contralateral to his paracentesis site. No flank or periumbilical ecchymoses were identified. Complete blood count demonstrated a white blood count (WBC) of 22,970/L, hematocrit 16%, and platelet count 104,000/L. INR was 2.0, unchanged from the last check on day 10. Partial thromboplastin time was 41 seconds and fibrinogen was 293 mg/dL (normal 150‐400 mg/dL). Peripheral blood smear was negative for red cell fragments. Blood chemistries revealed a sodium of 134 mg/dL, bicarbonate 20 mEq/L, anion gap 7, BUN 24 mg/dL, and creatinine 1.6 mg/dL (up from 1.0 mg/dL the previous day). His venous lactate level was 4.6 mmol/L and arterial blood gas sampling on room air demonstrated a pH of 7.35, partial pressure of carbon dioxide (pCO₂) 29 mmHg, partial pressure of oxygen (pCO₂) 54 mmHg, and bicarbonate 15 mEq/L. A femoral introducer was placed for volume resuscitation and the patient was urgently transfused with packed red blood cells (PRBCs) and fresh‐frozen plasma (FFP) to correct his coagulopathy. Computed tomography of the abdomen revealed a large left retroperitoneal hematoma measuring 15 15 22 cm³ (Figure 1). Despite transfusion, his hematocrit continued to fall. Urgent angiography was performed, upon which he was found to have active bleeding from the left L3‐L5 lumbar arteries. These were successfully embolized. He required PRBCs and FFP transfusion only once following this procedure. Given a transient decrease in his urine output, his bladder pressures were followed closely for evidence of abdominal compartment syndrome, which did not develop. He was transferred from the intensive care unit (ICU) to the floor on day 20, where his physical exam and hematocrit remained stable and his delirium slowly cleared. He was ultimately discharged to a skilled nursing facility on day 33.

Figure 1

Discussion

Spontaneous retroperitoneal hematoma is a well‐recognized entity that may present with the classic triad of abdominal or groin pain, palpable abdominal or flank mass, and shock or lower extremity motor or sensory changes due to femoral nerve compression.1 Although classically described as skin findings associated with retroperitoneal hemorrhage, Cullen and Grey‐Turner signs are relatively late findings that may not develop in all patients.

Retroperitoneal hemorrhage is well‐recognized as a result of iatrogenic anticoagulation,1 but has been reported less commonly as a result of coagulopathy related to cirrhosis. Di Bisceglie and Richart2 describe 2 patients with MELD scores of 29 and 25, respectively, who developed spontaneous retroperitoneal and rectus muscle hemorrhage. Both had evidence of associated disseminated intravascular coagulation (DIC) and died. Even less common is spontaneous lumbar artery rupture, occurring rarely in the absence of trauma or instrumentation. One reported bleed developed in the context of systemic anticoagulation for a mechanical valve.3 Halak et al.4 relate a case in which the only known risk factor was chronic renal disease. Hama et al.5 describe a patient with a history of alcoholic liver cirrhosis and INR of 2.3 whose lumbar artery rupture was successfully managed with transcatheter arterial embolization.

It is difficult to ascertain the effect of prophylactic anticoagulation in development of this particular hemorrhage. Retroperitoneal bleeding is a very rare complication of pharmacologic prophylaxis for DVT reported with both low‐molecular weight and unfractionated heparins.6 There may be additive risk of prophylaxis in a cirrhotic patient with baseline elevated INR and thrombocytopenia, particularly in the context of renal failure.

Options in the management of spontaneous retroperitoneal hematoma include transarterial embolization, percutaneous decompression, and open surgery. Nonoperative management of these bleeds when possible may be preferable in cirrhotic patients, as their baseline liver disease renders them higher‐risk candidates for surgery. There are no randomized trials comparing these approaches.1

In summary, we report the case of a 56‐year‐old man with end‐stage liver disease and associated coagulopathy without evidence of DIC who survived to discharge with intravascular management of a spontaneous retroperitoneal hemorrhage from the lumbar arteries. To our knowledge, this is the second reported case of spontaneous retroperitoneal hemorrhage in a cirrhotic in which the lumbar arteries were implicated and the first in which multiple arteries were found to be bleeding simultaneously. Any hospitalized patient who develops abdominal pain, flank pain, or hemodynamic instability in the context of coagulopathy, regardless of cause, warrants evaluation for retroperitoneal bleed. Appropriate early management includes immediate resuscitation, intensive monitoring, urgent imaging, and surgical and interventional radiology consultation in order to prevent a fatal outcome.

A 51‐year‐old African American woman with medical history of essential hypertension and chronic obstructive pulmonary disease (COPD) presented to the hospital with chest pain and shortness of breath. The chest pain was retrosternal and radiated to the back. It lasted for about an hour and resolved without any intervention. After some time, she again felt discomfort in the chest, which was a constant and dull ache.

She had similar episodes of chest pain 1 week prior, although less severe in intensity, for which she went to an outside hospital before coming to our hospital. Acute coronary syndrome was ruled out with serial cardiac enzymes measurements. An exercise stress test was also performed at that time, which failed to show any stress‐induced ischemia.

Her medications included lisinopril for hypertension and aspirin, which had been started 1 week prior to admission. She gave a 10‐pack‐year history of smoking tobacco. Family history was significant for hypertension in her father and coronary artery disease in her mother at the age of 58 years. A review of systems was negative for fever, cough, orthopnea, wheezing, palpitations, nausea, vomiting, recent surgery, or any significant trauma.

Assessment

The patient's physical examination was only remarkable for a blood pressure (BP) of 181/100 mm Hg. She did not have Marfanoid features, hyperflexible joints, or easy bruisability. Laboratory tests, including complete blood count, comprehensive metabolic panel, and cardiac enzymes, were within normal limits. A contrast‐enhanced computed tomography (CT) of the chest showed a linear hypodense area in the left lateral aspect of the main pulmonary trunk, which suggested an intimal dissection of the main pulmonary artery. Magnetic resonance angiography/emmaging (MRA/MRI) confirmed dissection of the main pulmonary artery extending into the proximal left pulmonary artery and associated with a 12 8 mm² aneurysm (Figures 1 and 2). The entry site of dissection was located in the main pulmonary artery just after its origin and the exit site was located in the left pulmonary artery 5 mm distal to the bifurcation of main pulmonary artery. The pulmonary artery diameter at the dissection was 27 mm.

Figure 1

Figure 2

Diagnosis

To investigate possible etiologies, a transthoracic echocardiogram with Doppler was done to look for pulmonary hypertension. The echocardiogram showed normal pulmonary artery pressure with normal right ventricular systolic pressure. There was no evidence of pericardial effusion or structural cardiac abnormality on echocardiogram. Further investigations including work up for connective tissue diseases and infectious etiologies (Table 1) were normal.

According to Shilkin et al.,1 Helmbrecht first reported pulmonary artery dissection (PAD) in 1842. PAD is very rare and is usually diagnosed at autopsy. There are 71 other cases of PAD reported in the English literature, of which 16 cases are in living patients.217 Unlike aortic dissection, which is fairly common, the reentry circuit for PAD is formed by the rupture of the free wall of the pulmonary artery leading to hemopericardium, cardiac tamponade, and sudden death.2, 8, 9 There is wide variation in age of incidence, ranging from 26 to 85 years of age, with a slightly higher prevalence in females (male‐to‐female ratio 1:1.2).1, 2 The main pulmonary artery is usually involved, with or without involvement of its branches. Isolated left and right pulmonary artery involvement is seen in 6% and 4% of cases, respectively.2

Pulmonary hypertension, either primary or secondary (collagen vascular diseases, COPD, congenital heart diseases, etc.), is the most common underlying etiology. Other less common, but well‐described etiologies include: Marfan's syndrome, instrumentation of pulmonary artery, tuberculosis, syphilis, pregnancy, idiopathic cystic medial necrosis, and amyloidosis.2, 8

As noted earlier, underlying pulmonary hypertension is usually a major risk factor for PAD. More than 75% of the patients have underlying acute or chronic pulmonary hypertension.2 Our patient had COPD without pulmonary hypertension. Despite extensive investigation, no underlying cause of her pulmonary dissection was identified. The differential diagnosis includes cryptogenic cystic medionecrosis; however, because the patient refused surgery the diagnosis remains unknown. As in our case, idiopathic PAD is extremely rare, and only 4 other cases have been described in the literature.2 Underlying etiologies should always be ruled out to identify correctable causes such as congenital abnormalities of the heart leading to pulmonary hypertension.

Chest pain is a very common presenting complaint in the emergency department. Although rare, PAD should be suspected in a patient with retrosternal chest pain when other common causes of chest pain are excluded. Some of the more suggestive findings are the presence of a new diastolic murmur, a wide mediastinum on chest x‐ray, and CT scan of chest showing an intimal flap.2, 8 CT scan of the chest is an acceptable imaging modality to diagnose PAD.18 According to Neimatallah et al.,18 there are only 5 cases in the literature reported with detailed CT scans demonstrating PAD. If the diagnosis remains uncertain, it should be confirmed by MRI/MRA.16 Transthoracic echocardiography can be used for diagnosis and follow‐up of conservatively managed patients with PAD.3, 8, 19 The echocardiographic findings suggestive of PAD include direct or indirect evidence of pulmonary artery hypertension, with a large main pulmonary artery and an intimal flap across the pulmonary trunk.

Management

No consensus strategy is available for the management of PAD because of the rarity of this condition. In general, operative repair is the treatment of choice for PAD.2, 8, 9, 11 There are 16 cases diagnosed in living patients, out of which 6 were managed medically, 8 were managed surgically, and management was not discussed in 2 of the case reports (Table 2). In these case reports, medically managed patients were treated with oxygen, vasodilators (nitrates, angiotensin‐converting enzyme [ACE] inhibitors, dihydropyridine calcium channel blockers, sildenafil), diuretics and beta‐blockers. These patients did well on follow‐up, ranging from 3 weeks to 4 years, except for 1 who died on day 4 in the intensive care unit (ICU).

Conservative management may be tried in patients who are hemodynamically stable and do not have pericardial effusion.2, 9 The aim of conservative management is to decrease right ventricular preload and afterload. Preload reduction can be dangerous in patients with PAD and should be done in the intensive care setting as this can lead to profound hypotension. Nitrates for preload reduction should be used cautiously in patients taking sildenafil or similar agents for erectile dysfunction or pulmonary artery hypertension because of significant risk of cardiovascular collapse. The American Heart Association and American College of Cardiology both recommend that there should be a time gap of at least 24 hours between the last dose of sildenafil and the first dose of nitrates. Conservatively managed patients should be followed with interval CT scans2, 9, 18 or echocardiography.3, 19 In addition, the underlying etiology should always be investigated to predict prognosis and recommend future management strategies.

The patient was offered surgical repair but she declined. She was managed conservatively with nitrates and beta‐blockers and was pain free within 24 hours. Her BP was brought down to a systolic BP range of 130140 mm Hg. A repeat CT scan of the chest at 1‐month follow up was unchanged. The patient was doing well at 6‐month follow‐up.

Conclusions

PAD is an extremely rare cause of chest pain and a rare antemortem diagnosis. It is usually associated with underlying pulmonary hypertension. This case describes a patient with PAD in the absence of pulmonary hypertension. The patient was managed with conservative medical therapy and did well at 6‐month follow‐up. There are a total of 6 other case reports of patients with PAD managed conservatively, out of which 5 patients did well at follow‐up and 1 patient died. More case reports and longer follow‐up are needed to assess the effectiveness of conservative medical therapy in patients with PAD. To our knowledge, this is the first case report of idiopathic PAD diagnosed in a living patient and managed conservatively. This case also highlights better prognosis for patients with PAD without underlying pulmonary hypertension.

A 51‐year‐old African American woman with medical history of essential hypertension and chronic obstructive pulmonary disease (COPD) presented to the hospital with chest pain and shortness of breath. The chest pain was retrosternal and radiated to the back. It lasted for about an hour and resolved without any intervention. After some time, she again felt discomfort in the chest, which was a constant and dull ache.

She had similar episodes of chest pain 1 week prior, although less severe in intensity, for which she went to an outside hospital before coming to our hospital. Acute coronary syndrome was ruled out with serial cardiac enzymes measurements. An exercise stress test was also performed at that time, which failed to show any stress‐induced ischemia.

Her medications included lisinopril for hypertension and aspirin, which had been started 1 week prior to admission. She gave a 10‐pack‐year history of smoking tobacco. Family history was significant for hypertension in her father and coronary artery disease in her mother at the age of 58 years. A review of systems was negative for fever, cough, orthopnea, wheezing, palpitations, nausea, vomiting, recent surgery, or any significant trauma.

Assessment

The patient's physical examination was only remarkable for a blood pressure (BP) of 181/100 mm Hg. She did not have Marfanoid features, hyperflexible joints, or easy bruisability. Laboratory tests, including complete blood count, comprehensive metabolic panel, and cardiac enzymes, were within normal limits. A contrast‐enhanced computed tomography (CT) of the chest showed a linear hypodense area in the left lateral aspect of the main pulmonary trunk, which suggested an intimal dissection of the main pulmonary artery. Magnetic resonance angiography/emmaging (MRA/MRI) confirmed dissection of the main pulmonary artery extending into the proximal left pulmonary artery and associated with a 12 8 mm² aneurysm (Figures 1 and 2). The entry site of dissection was located in the main pulmonary artery just after its origin and the exit site was located in the left pulmonary artery 5 mm distal to the bifurcation of main pulmonary artery. The pulmonary artery diameter at the dissection was 27 mm.

Figure 1

Figure 2

Diagnosis

To investigate possible etiologies, a transthoracic echocardiogram with Doppler was done to look for pulmonary hypertension. The echocardiogram showed normal pulmonary artery pressure with normal right ventricular systolic pressure. There was no evidence of pericardial effusion or structural cardiac abnormality on echocardiogram. Further investigations including work up for connective tissue diseases and infectious etiologies (Table 1) were normal.

According to Shilkin et al.,1 Helmbrecht first reported pulmonary artery dissection (PAD) in 1842. PAD is very rare and is usually diagnosed at autopsy. There are 71 other cases of PAD reported in the English literature, of which 16 cases are in living patients.217 Unlike aortic dissection, which is fairly common, the reentry circuit for PAD is formed by the rupture of the free wall of the pulmonary artery leading to hemopericardium, cardiac tamponade, and sudden death.2, 8, 9 There is wide variation in age of incidence, ranging from 26 to 85 years of age, with a slightly higher prevalence in females (male‐to‐female ratio 1:1.2).1, 2 The main pulmonary artery is usually involved, with or without involvement of its branches. Isolated left and right pulmonary artery involvement is seen in 6% and 4% of cases, respectively.2

Pulmonary hypertension, either primary or secondary (collagen vascular diseases, COPD, congenital heart diseases, etc.), is the most common underlying etiology. Other less common, but well‐described etiologies include: Marfan's syndrome, instrumentation of pulmonary artery, tuberculosis, syphilis, pregnancy, idiopathic cystic medial necrosis, and amyloidosis.2, 8

As noted earlier, underlying pulmonary hypertension is usually a major risk factor for PAD. More than 75% of the patients have underlying acute or chronic pulmonary hypertension.2 Our patient had COPD without pulmonary hypertension. Despite extensive investigation, no underlying cause of her pulmonary dissection was identified. The differential diagnosis includes cryptogenic cystic medionecrosis; however, because the patient refused surgery the diagnosis remains unknown. As in our case, idiopathic PAD is extremely rare, and only 4 other cases have been described in the literature.2 Underlying etiologies should always be ruled out to identify correctable causes such as congenital abnormalities of the heart leading to pulmonary hypertension.

Chest pain is a very common presenting complaint in the emergency department. Although rare, PAD should be suspected in a patient with retrosternal chest pain when other common causes of chest pain are excluded. Some of the more suggestive findings are the presence of a new diastolic murmur, a wide mediastinum on chest x‐ray, and CT scan of chest showing an intimal flap.2, 8 CT scan of the chest is an acceptable imaging modality to diagnose PAD.18 According to Neimatallah et al.,18 there are only 5 cases in the literature reported with detailed CT scans demonstrating PAD. If the diagnosis remains uncertain, it should be confirmed by MRI/MRA.16 Transthoracic echocardiography can be used for diagnosis and follow‐up of conservatively managed patients with PAD.3, 8, 19 The echocardiographic findings suggestive of PAD include direct or indirect evidence of pulmonary artery hypertension, with a large main pulmonary artery and an intimal flap across the pulmonary trunk.

Management

No consensus strategy is available for the management of PAD because of the rarity of this condition. In general, operative repair is the treatment of choice for PAD.2, 8, 9, 11 There are 16 cases diagnosed in living patients, out of which 6 were managed medically, 8 were managed surgically, and management was not discussed in 2 of the case reports (Table 2). In these case reports, medically managed patients were treated with oxygen, vasodilators (nitrates, angiotensin‐converting enzyme [ACE] inhibitors, dihydropyridine calcium channel blockers, sildenafil), diuretics and beta‐blockers. These patients did well on follow‐up, ranging from 3 weeks to 4 years, except for 1 who died on day 4 in the intensive care unit (ICU).

Conservative management may be tried in patients who are hemodynamically stable and do not have pericardial effusion.2, 9 The aim of conservative management is to decrease right ventricular preload and afterload. Preload reduction can be dangerous in patients with PAD and should be done in the intensive care setting as this can lead to profound hypotension. Nitrates for preload reduction should be used cautiously in patients taking sildenafil or similar agents for erectile dysfunction or pulmonary artery hypertension because of significant risk of cardiovascular collapse. The American Heart Association and American College of Cardiology both recommend that there should be a time gap of at least 24 hours between the last dose of sildenafil and the first dose of nitrates. Conservatively managed patients should be followed with interval CT scans2, 9, 18 or echocardiography.3, 19 In addition, the underlying etiology should always be investigated to predict prognosis and recommend future management strategies.

The patient was offered surgical repair but she declined. She was managed conservatively with nitrates and beta‐blockers and was pain free within 24 hours. Her BP was brought down to a systolic BP range of 130140 mm Hg. A repeat CT scan of the chest at 1‐month follow up was unchanged. The patient was doing well at 6‐month follow‐up.

Conclusions

PAD is an extremely rare cause of chest pain and a rare antemortem diagnosis. It is usually associated with underlying pulmonary hypertension. This case describes a patient with PAD in the absence of pulmonary hypertension. The patient was managed with conservative medical therapy and did well at 6‐month follow‐up. There are a total of 6 other case reports of patients with PAD managed conservatively, out of which 5 patients did well at follow‐up and 1 patient died. More case reports and longer follow‐up are needed to assess the effectiveness of conservative medical therapy in patients with PAD. To our knowledge, this is the first case report of idiopathic PAD diagnosed in a living patient and managed conservatively. This case also highlights better prognosis for patients with PAD without underlying pulmonary hypertension.

A 51‐year‐old African American woman with medical history of essential hypertension and chronic obstructive pulmonary disease (COPD) presented to the hospital with chest pain and shortness of breath. The chest pain was retrosternal and radiated to the back. It lasted for about an hour and resolved without any intervention. After some time, she again felt discomfort in the chest, which was a constant and dull ache.

She had similar episodes of chest pain 1 week prior, although less severe in intensity, for which she went to an outside hospital before coming to our hospital. Acute coronary syndrome was ruled out with serial cardiac enzymes measurements. An exercise stress test was also performed at that time, which failed to show any stress‐induced ischemia.

Her medications included lisinopril for hypertension and aspirin, which had been started 1 week prior to admission. She gave a 10‐pack‐year history of smoking tobacco. Family history was significant for hypertension in her father and coronary artery disease in her mother at the age of 58 years. A review of systems was negative for fever, cough, orthopnea, wheezing, palpitations, nausea, vomiting, recent surgery, or any significant trauma.

Assessment

The patient's physical examination was only remarkable for a blood pressure (BP) of 181/100 mm Hg. She did not have Marfanoid features, hyperflexible joints, or easy bruisability. Laboratory tests, including complete blood count, comprehensive metabolic panel, and cardiac enzymes, were within normal limits. A contrast‐enhanced computed tomography (CT) of the chest showed a linear hypodense area in the left lateral aspect of the main pulmonary trunk, which suggested an intimal dissection of the main pulmonary artery. Magnetic resonance angiography/emmaging (MRA/MRI) confirmed dissection of the main pulmonary artery extending into the proximal left pulmonary artery and associated with a 12 8 mm² aneurysm (Figures 1 and 2). The entry site of dissection was located in the main pulmonary artery just after its origin and the exit site was located in the left pulmonary artery 5 mm distal to the bifurcation of main pulmonary artery. The pulmonary artery diameter at the dissection was 27 mm.

Figure 1

Figure 2

Diagnosis

To investigate possible etiologies, a transthoracic echocardiogram with Doppler was done to look for pulmonary hypertension. The echocardiogram showed normal pulmonary artery pressure with normal right ventricular systolic pressure. There was no evidence of pericardial effusion or structural cardiac abnormality on echocardiogram. Further investigations including work up for connective tissue diseases and infectious etiologies (Table 1) were normal.

According to Shilkin et al.,1 Helmbrecht first reported pulmonary artery dissection (PAD) in 1842. PAD is very rare and is usually diagnosed at autopsy. There are 71 other cases of PAD reported in the English literature, of which 16 cases are in living patients.217 Unlike aortic dissection, which is fairly common, the reentry circuit for PAD is formed by the rupture of the free wall of the pulmonary artery leading to hemopericardium, cardiac tamponade, and sudden death.2, 8, 9 There is wide variation in age of incidence, ranging from 26 to 85 years of age, with a slightly higher prevalence in females (male‐to‐female ratio 1:1.2).1, 2 The main pulmonary artery is usually involved, with or without involvement of its branches. Isolated left and right pulmonary artery involvement is seen in 6% and 4% of cases, respectively.2

Pulmonary hypertension, either primary or secondary (collagen vascular diseases, COPD, congenital heart diseases, etc.), is the most common underlying etiology. Other less common, but well‐described etiologies include: Marfan's syndrome, instrumentation of pulmonary artery, tuberculosis, syphilis, pregnancy, idiopathic cystic medial necrosis, and amyloidosis.2, 8

As noted earlier, underlying pulmonary hypertension is usually a major risk factor for PAD. More than 75% of the patients have underlying acute or chronic pulmonary hypertension.2 Our patient had COPD without pulmonary hypertension. Despite extensive investigation, no underlying cause of her pulmonary dissection was identified. The differential diagnosis includes cryptogenic cystic medionecrosis; however, because the patient refused surgery the diagnosis remains unknown. As in our case, idiopathic PAD is extremely rare, and only 4 other cases have been described in the literature.2 Underlying etiologies should always be ruled out to identify correctable causes such as congenital abnormalities of the heart leading to pulmonary hypertension.

Chest pain is a very common presenting complaint in the emergency department. Although rare, PAD should be suspected in a patient with retrosternal chest pain when other common causes of chest pain are excluded. Some of the more suggestive findings are the presence of a new diastolic murmur, a wide mediastinum on chest x‐ray, and CT scan of chest showing an intimal flap.2, 8 CT scan of the chest is an acceptable imaging modality to diagnose PAD.18 According to Neimatallah et al.,18 there are only 5 cases in the literature reported with detailed CT scans demonstrating PAD. If the diagnosis remains uncertain, it should be confirmed by MRI/MRA.16 Transthoracic echocardiography can be used for diagnosis and follow‐up of conservatively managed patients with PAD.3, 8, 19 The echocardiographic findings suggestive of PAD include direct or indirect evidence of pulmonary artery hypertension, with a large main pulmonary artery and an intimal flap across the pulmonary trunk.

Management

No consensus strategy is available for the management of PAD because of the rarity of this condition. In general, operative repair is the treatment of choice for PAD.2, 8, 9, 11 There are 16 cases diagnosed in living patients, out of which 6 were managed medically, 8 were managed surgically, and management was not discussed in 2 of the case reports (Table 2). In these case reports, medically managed patients were treated with oxygen, vasodilators (nitrates, angiotensin‐converting enzyme [ACE] inhibitors, dihydropyridine calcium channel blockers, sildenafil), diuretics and beta‐blockers. These patients did well on follow‐up, ranging from 3 weeks to 4 years, except for 1 who died on day 4 in the intensive care unit (ICU).

Conservative management may be tried in patients who are hemodynamically stable and do not have pericardial effusion.2, 9 The aim of conservative management is to decrease right ventricular preload and afterload. Preload reduction can be dangerous in patients with PAD and should be done in the intensive care setting as this can lead to profound hypotension. Nitrates for preload reduction should be used cautiously in patients taking sildenafil or similar agents for erectile dysfunction or pulmonary artery hypertension because of significant risk of cardiovascular collapse. The American Heart Association and American College of Cardiology both recommend that there should be a time gap of at least 24 hours between the last dose of sildenafil and the first dose of nitrates. Conservatively managed patients should be followed with interval CT scans2, 9, 18 or echocardiography.3, 19 In addition, the underlying etiology should always be investigated to predict prognosis and recommend future management strategies.

The patient was offered surgical repair but she declined. She was managed conservatively with nitrates and beta‐blockers and was pain free within 24 hours. Her BP was brought down to a systolic BP range of 130140 mm Hg. A repeat CT scan of the chest at 1‐month follow up was unchanged. The patient was doing well at 6‐month follow‐up.

Conclusions

PAD is an extremely rare cause of chest pain and a rare antemortem diagnosis. It is usually associated with underlying pulmonary hypertension. This case describes a patient with PAD in the absence of pulmonary hypertension. The patient was managed with conservative medical therapy and did well at 6‐month follow‐up. There are a total of 6 other case reports of patients with PAD managed conservatively, out of which 5 patients did well at follow‐up and 1 patient died. More case reports and longer follow‐up are needed to assess the effectiveness of conservative medical therapy in patients with PAD. To our knowledge, this is the first case report of idiopathic PAD diagnosed in a living patient and managed conservatively. This case also highlights better prognosis for patients with PAD without underlying pulmonary hypertension.