The Clinical Picture

A 26-year-old woman presents with the sudden onset of left chest pain and dyspnea while at rest. She has never smoked. Two months ago, she developed a right-sided pneumothorax, which was treated with a tube thoracostomy. At that time, she received a diagnosis of tuberous sclerosis complex.

She has no other medical problems, has no history of trauma, and has tested negative for human immunodeficiency virus (HIV).

On physical examination, her breath sounds in the left hemithorax are decreased. She also has many nodular lesions on her face (Figure 1), a hypopigmented lesion on her right thigh (Figure 2), and a fleshy plaque on her lower back (Figure 3).

Radiography (Figure 4) and computed tomography (CT) of the chest (Figure 5) reveal a left-sided pneumothorax, a small right-sided pneumothorax, and diffuse, bilateral, thin-walled cysts in the lung.

Q: Which is the most likely diagnosis?

• Pulmonary Langerhans cell histiocytosis
• Cystic fibrosis
• Pneumocystis jirovecii pneumonia
• Alpha-1 antitrypsin deficiency
• Tuberous sclerosis complex with lymphangioleiomyomatosis

A: The correct diagnosis is tuberous sclerosis complex with lymphangioleiomyomatosis. The lymphangioleiomyomatosis was suggested by the CT findings, by the recurrence of pneumothorax, and, later, by biopsy results. Lymphangioleiomyomatosis occurs in about 30% of women with the tuberous sclerosis complex.1 However, 10% to 15% of women with lymphangioleiomyomatosis do not have tuberous sclerosis complex, 2 in which case the condition is called sporadic lymphangioleiomyomatosis.

Tuberous sclerosis complex can involve the nerves (seizures, brain tumors), the lungs (lymphangioleiomyomatosis, causing pneumothorax or chylothorax), and the skin; skin lesions include facial angiofibromas (Figure 1), ash-leaf spot (Figure 2), and shagreen patch (Figure 3). It is also associated with abdominal involvement (lymphangiomyomas, renal angiomyolipomas).³

Lymphangioleiomyomatosis usually presents as spontaneous pneumothorax in women of childbearing age. After initial stabilization of pneumothorax with simple aspiration or thoracostomy, the patient should undergo ipsilateral chemical or surgical pleurodesis, as the risk of recurrent pneumothorax is greater than 70%.⁴ Single or bilateral lung transplantation has been accepted as therapy for end-stage pulmonary lymphangioleiomyomatosis, characterized by recurrent pneumothoraces and chylous pleural fluid collections causing respiratory failure (marked dyspnea, hypoxemia, and reductions in forced expiratory volume in the first second of expiration and in diffusing capacity for carbon monoxide. Recurrence of lymphangioleiomyomatosis in the allograft lung is rare.⁵ Hormone therapies such as intramuscular progesterone, oral progestins, or gonadotropin-releasing hormone agonists have been used for lymphangioleiomyomatosis (not pneumothorax), but they are no longer recommended.

Pulmonary Langerhans cell histiocytosis, cystic fibrosis, Pneumocystis jirovecii pneumonia, and alpha-1 antitrypsin deficiency have all been associated with spontaneous pneumothorax.

Pulmonary Langerhans cell histiocytosis can affect multiple systems, including lung, skin, bone, and the pituitary gland. More than 90% of patients have a history of smoking.⁶ Chest radiography reveals a reticulonodular pattern with involvement of the middle and upper lobes. Later, the nodules tend to cavitate and form contiguous cysts that may mimic lymphangioleiomyomatosis on a high-resolution chest CT.

Cystic fibrosis is most often diagnosed before the age of 3.⁷ In adults, it can present as sinus and pulmonary disease (chronic cough with sputum production, chronic sinusitis with nasal polyposis, radiographic evidence of bronchiectasis and, less commonly, pneumothorax); as a gastrointestinal tract and nutritional abnormality (pancreatic insufficiency, distal intestinal obstruction, focal biliary cirrhosis); and as male infertility.

Pneumocystis jiroveciipneumonia occurs mainly in patients on chronic immunosuppressive drugs or with immune deficiency due to HIV infection. Typical radiographic features are bilateral perihilar interstitial infiltrates that become increasingly homogeneous and diffuse as the disease progresses. Less common findings include solitary or multiple nodules, upper-lobe infiltrates in patients receiving aerosolized pentamidine (NebuPent), pneumatoceles, and pneumothorax.⁸

Alpha-1 antitrypsin is an inhibitor of neutrophil elastase. Deficiency is associated with severe, early-onset panacinar emphysema with a basilar predominance, with chronic liver disease including cirrhosis, and less commonly with panniculitis and vasculitis associated with antineutrophil cytoplasmic antibody.⁹ Coalescence of panacinar emphysema leads to the formation of bullae and is important in the development of spontaneous pneumothorax.¹⁰

The patient underwent bilateral talc pleurodesis. Lung biopsy at the same time confirmed lymphangioleiomyomatosis. One month later, the right pneumothorax recurred, and she underwent pleurodesis in the right hemithorax with tetracycline. Six months after the second pleurodesis, she was asymptomatic.

A 26-year-old woman presents with the sudden onset of left chest pain and dyspnea while at rest. She has never smoked. Two months ago, she developed a right-sided pneumothorax, which was treated with a tube thoracostomy. At that time, she received a diagnosis of tuberous sclerosis complex.

She has no other medical problems, has no history of trauma, and has tested negative for human immunodeficiency virus (HIV).

On physical examination, her breath sounds in the left hemithorax are decreased. She also has many nodular lesions on her face (Figure 1), a hypopigmented lesion on her right thigh (Figure 2), and a fleshy plaque on her lower back (Figure 3).

Radiography (Figure 4) and computed tomography (CT) of the chest (Figure 5) reveal a left-sided pneumothorax, a small right-sided pneumothorax, and diffuse, bilateral, thin-walled cysts in the lung.

Q: Which is the most likely diagnosis?

• Pulmonary Langerhans cell histiocytosis
• Cystic fibrosis
• Pneumocystis jirovecii pneumonia
• Alpha-1 antitrypsin deficiency
• Tuberous sclerosis complex with lymphangioleiomyomatosis

A: The correct diagnosis is tuberous sclerosis complex with lymphangioleiomyomatosis. The lymphangioleiomyomatosis was suggested by the CT findings, by the recurrence of pneumothorax, and, later, by biopsy results. Lymphangioleiomyomatosis occurs in about 30% of women with the tuberous sclerosis complex.1 However, 10% to 15% of women with lymphangioleiomyomatosis do not have tuberous sclerosis complex, 2 in which case the condition is called sporadic lymphangioleiomyomatosis.

Tuberous sclerosis complex can involve the nerves (seizures, brain tumors), the lungs (lymphangioleiomyomatosis, causing pneumothorax or chylothorax), and the skin; skin lesions include facial angiofibromas (Figure 1), ash-leaf spot (Figure 2), and shagreen patch (Figure 3). It is also associated with abdominal involvement (lymphangiomyomas, renal angiomyolipomas).³

Lymphangioleiomyomatosis usually presents as spontaneous pneumothorax in women of childbearing age. After initial stabilization of pneumothorax with simple aspiration or thoracostomy, the patient should undergo ipsilateral chemical or surgical pleurodesis, as the risk of recurrent pneumothorax is greater than 70%.⁴ Single or bilateral lung transplantation has been accepted as therapy for end-stage pulmonary lymphangioleiomyomatosis, characterized by recurrent pneumothoraces and chylous pleural fluid collections causing respiratory failure (marked dyspnea, hypoxemia, and reductions in forced expiratory volume in the first second of expiration and in diffusing capacity for carbon monoxide. Recurrence of lymphangioleiomyomatosis in the allograft lung is rare.⁵ Hormone therapies such as intramuscular progesterone, oral progestins, or gonadotropin-releasing hormone agonists have been used for lymphangioleiomyomatosis (not pneumothorax), but they are no longer recommended.

Pulmonary Langerhans cell histiocytosis, cystic fibrosis, Pneumocystis jirovecii pneumonia, and alpha-1 antitrypsin deficiency have all been associated with spontaneous pneumothorax.

Pulmonary Langerhans cell histiocytosis can affect multiple systems, including lung, skin, bone, and the pituitary gland. More than 90% of patients have a history of smoking.⁶ Chest radiography reveals a reticulonodular pattern with involvement of the middle and upper lobes. Later, the nodules tend to cavitate and form contiguous cysts that may mimic lymphangioleiomyomatosis on a high-resolution chest CT.

Cystic fibrosis is most often diagnosed before the age of 3.⁷ In adults, it can present as sinus and pulmonary disease (chronic cough with sputum production, chronic sinusitis with nasal polyposis, radiographic evidence of bronchiectasis and, less commonly, pneumothorax); as a gastrointestinal tract and nutritional abnormality (pancreatic insufficiency, distal intestinal obstruction, focal biliary cirrhosis); and as male infertility.

Pneumocystis jiroveciipneumonia occurs mainly in patients on chronic immunosuppressive drugs or with immune deficiency due to HIV infection. Typical radiographic features are bilateral perihilar interstitial infiltrates that become increasingly homogeneous and diffuse as the disease progresses. Less common findings include solitary or multiple nodules, upper-lobe infiltrates in patients receiving aerosolized pentamidine (NebuPent), pneumatoceles, and pneumothorax.⁸

Alpha-1 antitrypsin is an inhibitor of neutrophil elastase. Deficiency is associated with severe, early-onset panacinar emphysema with a basilar predominance, with chronic liver disease including cirrhosis, and less commonly with panniculitis and vasculitis associated with antineutrophil cytoplasmic antibody.⁹ Coalescence of panacinar emphysema leads to the formation of bullae and is important in the development of spontaneous pneumothorax.¹⁰

The patient underwent bilateral talc pleurodesis. Lung biopsy at the same time confirmed lymphangioleiomyomatosis. One month later, the right pneumothorax recurred, and she underwent pleurodesis in the right hemithorax with tetracycline. Six months after the second pleurodesis, she was asymptomatic.

A 26-year-old woman presents with the sudden onset of left chest pain and dyspnea while at rest. She has never smoked. Two months ago, she developed a right-sided pneumothorax, which was treated with a tube thoracostomy. At that time, she received a diagnosis of tuberous sclerosis complex.

She has no other medical problems, has no history of trauma, and has tested negative for human immunodeficiency virus (HIV).

On physical examination, her breath sounds in the left hemithorax are decreased. She also has many nodular lesions on her face (Figure 1), a hypopigmented lesion on her right thigh (Figure 2), and a fleshy plaque on her lower back (Figure 3).

Radiography (Figure 4) and computed tomography (CT) of the chest (Figure 5) reveal a left-sided pneumothorax, a small right-sided pneumothorax, and diffuse, bilateral, thin-walled cysts in the lung.

Q: Which is the most likely diagnosis?

• Pulmonary Langerhans cell histiocytosis
• Cystic fibrosis
• Pneumocystis jirovecii pneumonia
• Alpha-1 antitrypsin deficiency
• Tuberous sclerosis complex with lymphangioleiomyomatosis

A: The correct diagnosis is tuberous sclerosis complex with lymphangioleiomyomatosis. The lymphangioleiomyomatosis was suggested by the CT findings, by the recurrence of pneumothorax, and, later, by biopsy results. Lymphangioleiomyomatosis occurs in about 30% of women with the tuberous sclerosis complex.1 However, 10% to 15% of women with lymphangioleiomyomatosis do not have tuberous sclerosis complex, 2 in which case the condition is called sporadic lymphangioleiomyomatosis.

Tuberous sclerosis complex can involve the nerves (seizures, brain tumors), the lungs (lymphangioleiomyomatosis, causing pneumothorax or chylothorax), and the skin; skin lesions include facial angiofibromas (Figure 1), ash-leaf spot (Figure 2), and shagreen patch (Figure 3). It is also associated with abdominal involvement (lymphangiomyomas, renal angiomyolipomas).³

Lymphangioleiomyomatosis usually presents as spontaneous pneumothorax in women of childbearing age. After initial stabilization of pneumothorax with simple aspiration or thoracostomy, the patient should undergo ipsilateral chemical or surgical pleurodesis, as the risk of recurrent pneumothorax is greater than 70%.⁴ Single or bilateral lung transplantation has been accepted as therapy for end-stage pulmonary lymphangioleiomyomatosis, characterized by recurrent pneumothoraces and chylous pleural fluid collections causing respiratory failure (marked dyspnea, hypoxemia, and reductions in forced expiratory volume in the first second of expiration and in diffusing capacity for carbon monoxide. Recurrence of lymphangioleiomyomatosis in the allograft lung is rare.⁵ Hormone therapies such as intramuscular progesterone, oral progestins, or gonadotropin-releasing hormone agonists have been used for lymphangioleiomyomatosis (not pneumothorax), but they are no longer recommended.

Pulmonary Langerhans cell histiocytosis, cystic fibrosis, Pneumocystis jirovecii pneumonia, and alpha-1 antitrypsin deficiency have all been associated with spontaneous pneumothorax.

Pulmonary Langerhans cell histiocytosis can affect multiple systems, including lung, skin, bone, and the pituitary gland. More than 90% of patients have a history of smoking.⁶ Chest radiography reveals a reticulonodular pattern with involvement of the middle and upper lobes. Later, the nodules tend to cavitate and form contiguous cysts that may mimic lymphangioleiomyomatosis on a high-resolution chest CT.

Cystic fibrosis is most often diagnosed before the age of 3.⁷ In adults, it can present as sinus and pulmonary disease (chronic cough with sputum production, chronic sinusitis with nasal polyposis, radiographic evidence of bronchiectasis and, less commonly, pneumothorax); as a gastrointestinal tract and nutritional abnormality (pancreatic insufficiency, distal intestinal obstruction, focal biliary cirrhosis); and as male infertility.

Pneumocystis jiroveciipneumonia occurs mainly in patients on chronic immunosuppressive drugs or with immune deficiency due to HIV infection. Typical radiographic features are bilateral perihilar interstitial infiltrates that become increasingly homogeneous and diffuse as the disease progresses. Less common findings include solitary or multiple nodules, upper-lobe infiltrates in patients receiving aerosolized pentamidine (NebuPent), pneumatoceles, and pneumothorax.⁸

Alpha-1 antitrypsin is an inhibitor of neutrophil elastase. Deficiency is associated with severe, early-onset panacinar emphysema with a basilar predominance, with chronic liver disease including cirrhosis, and less commonly with panniculitis and vasculitis associated with antineutrophil cytoplasmic antibody.⁹ Coalescence of panacinar emphysema leads to the formation of bullae and is important in the development of spontaneous pneumothorax.¹⁰

The patient underwent bilateral talc pleurodesis. Lung biopsy at the same time confirmed lymphangioleiomyomatosis. One month later, the right pneumothorax recurred, and she underwent pleurodesis in the right hemithorax with tetracycline. Six months after the second pleurodesis, she was asymptomatic.

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Angiography showed 99% stenosis of the first diagonal branch of the left anterior descending (LAD) artery (Figure 1). No evidence of underlying atherosclerotic disease was seen, suggesting that the obstruction was due to embolism rather than to in situ thrombosis occurring after plaque rupture. The thrombus was aspirated from the vessel. Stenting was not needed, as there was no residual stenosis (Figure 2).

Transesophageal echocardiography, done to find the source of the embolus, showed a small, mobile echo-density on the anterior mitral valve leaflet, with no apparent thrombus or patent foramen ovale.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Angiography showed 99% stenosis of the first diagonal branch of the left anterior descending (LAD) artery (Figure 1). No evidence of underlying atherosclerotic disease was seen, suggesting that the obstruction was due to embolism rather than to in situ thrombosis occurring after plaque rupture. The thrombus was aspirated from the vessel. Stenting was not needed, as there was no residual stenosis (Figure 2).

Transesophageal echocardiography, done to find the source of the embolus, showed a small, mobile echo-density on the anterior mitral valve leaflet, with no apparent thrombus or patent foramen ovale.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Angiography showed 99% stenosis of the first diagonal branch of the left anterior descending (LAD) artery (Figure 1). No evidence of underlying atherosclerotic disease was seen, suggesting that the obstruction was due to embolism rather than to in situ thrombosis occurring after plaque rupture. The thrombus was aspirated from the vessel. Stenting was not needed, as there was no residual stenosis (Figure 2).

Transesophageal echocardiography, done to find the source of the embolus, showed a small, mobile echo-density on the anterior mitral valve leaflet, with no apparent thrombus or patent foramen ovale.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The physical examination is normal. Chest radiography reveals a 1-cm-wide bony bridge between the third and the fourth ribs, anteriorly and on the right (Figure 1), but no signs of trauma, rib fracture, or callus formation. Computed tomography to evaluate the hemoptysis shows no evidence of trauma or fracture.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The physical examination is normal. Chest radiography reveals a 1-cm-wide bony bridge between the third and the fourth ribs, anteriorly and on the right (Figure 1), but no signs of trauma, rib fracture, or callus formation. Computed tomography to evaluate the hemoptysis shows no evidence of trauma or fracture.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The physical examination is normal. Chest radiography reveals a 1-cm-wide bony bridge between the third and the fourth ribs, anteriorly and on the right (Figure 1), but no signs of trauma, rib fracture, or callus formation. Computed tomography to evaluate the hemoptysis shows no evidence of trauma or fracture.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

A 78-year-old man with hyperuricemia treated with allopurinol (Zyloprim) presented with asymptomatic nodules on both hands (Figure 1), with progressive growth for 2 years.

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

A 78-year-old man with hyperuricemia treated with allopurinol (Zyloprim) presented with asymptomatic nodules on both hands (Figure 1), with progressive growth for 2 years.

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

A 78-year-old man with hyperuricemia treated with allopurinol (Zyloprim) presented with asymptomatic nodules on both hands (Figure 1), with progressive growth for 2 years.

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

A healthy 47-year-old woman presents with a 3-day history of widespread asymptomatic lesions in the extremities, fever, arthralgias, and mild abdominal pain. A physical examination reveals a symmetric rash in the lower legs with erythematous purple papules. These papules do not blanch when pressure is applied and so are clinically compatible with palpable purpura (Figure 1). Skin biopsy shows leukocytoclastic vasculitis with immunoglobulin A (IgA) deposits in the vascular wall.

Q: Which is the most likely diagnosis?

• Idiopathic thrombocytopenic purpura
• Vitamin C deficiency (scurvy)
• Kaposi sarcoma not related to human immunodeficiency virus (HIV) infection
• Henoch-Schönlein purpura
• Polyarteritis nodosa

A: The correct answer is Henoch-Schönlein purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disease caused by specific antibodies against platelet-membrane glycoproteins. It is characterized by thrombocytopenia not explainable by contact with toxic substances or by other causes. Along with nonpalpable purpura, other common signs are epistaxis, gingival bleeding, menorrhagia, and retinal hemorrhage.

Scurvy is an uncommon deficiency of ascorbic acid (vitamin C). The elderly and alcoholics are at higher risk, as they do not take in enough vitamin C in the diet. Patients usually show perifollicular hemorrhages of the skin and mucous membranes, typically petechial hemorrhage or ecchymosis of the gums around the upper incisors. Other cutaneous signs are follicular hyperkeratosis on the forearms, small corkscrew hairs, and sicca syndrome, which is more common in adults.

Non-HIV Kaposi sarcoma usually affects elderly patients, with pink, red, or brown papules or nodules on the legs and, less commonly, on the head and neck. Histopathologic examination shows newly formed irregular blood vessels with an inflammatory infiltrate of plasma cells and lymphocytes; immunohistochemical human herpes virus staining is usually positive.

Polyarteritis nodosa is a systemic vasculitis that affects medium or small arteries with necrotizing inflammation; renal glomeruli and arterioles, capillaries, and venules are unaffected. Skin manifestations include palpable purpura, livedo reticularis, ulcers, and distal gangrene. The condition also usually affects the kidneys, the heart, and the musculoskeletal and nervous systems.

 

A SYSTEMIC VASCULITIS

Henoch-Schönlein purpura is a systemic vasculitis affecting the skin, gastrointestinal tract, kidneys, and joints. Palpable purpura and joint pain are the most common and consistent presenting symptoms. The kidneys are affected in about one-third of children and in 60% of adults, and this is the major factor determining the long-term outcome.¹

In our patient, laboratory testing that included a complete blood cell count, biochemical testing (including IgA levels), urinary sediment, and coagulation studies showed no abnormalities except elevations of the erythrocyte sedimentation rate and the concentration of C-reactive protein (an acute-phase reactant). These can be normal in some patients. Renal involvement was also not present.

DIAGNOSIS

The diagnosis relies on clinical manifestations. Because Henoch-Schönlein purpura is less common in adults, biopsy plays a more important role in establishing the diagnosis in this age group, and it does this by demonstrating leukocytoclastic vasculitis with a predominance of IgA deposition under immunofluorescence. Recent studies in children showed that an elevated IgA concentration along with reduced IgM levels was associated with a higher rate of severe complications.² However, depending on the age of the biopsied lesion, IgA may not be detected.

TREATMENT DIRECTED AT SYMPTOMS

Our patient received oral corticosteroids 0.5 mg/kg per day for 20 days, and the lesions resolved by 4 weeks.

Management of Henoch-Schönlein purpura is mainly directed at the symptoms, with oral hydration and nonsteroidal anti-inflammatory drugs. For severe cases, a short course of corticosteroids (0.5–1 mg/kg) may be used.

Although no controlled clinical trial has proven that Henoch-Schönlein purpura responds to corticosteroids, colchicine, or other drugs, corticosteroids are used most often, especially in patients with renal disease. Patients with severe renal insufficiency, abdominal pain, joint involvement, or bleeding should be hospitalized. Plasmapheresis³ has been used in severe cases.

HENOCH-SCHÖNLEIN PURPURA AND MALIGNANCY

During a follow-up evaluation 1 month later, our patient was diagnosed with adenocarcinoma of the breast. This highlights the value of a workup for cancer in adults with cutaneous vasculitis.

Cutaneous vasculitis can represent a paraneoplastic syndrome associated with a malignant tumor. The pathophysiology of this association is unclear, but one proposed mechanism is the exaggerated production of antibodies that react against tumor neoantigens, leading to the formation of immune complexes, or that occasionally recognize endothelial cells because of similarities with tumor antigens. Another theory is that abnormally high levels of inflammatory cytokines are produced by neoplastic cells or in response to decreased immune complex clearance.

Yet another theory is that hyperviscosity of the blood, seen in some cancers, increases the contact time for deposition of immune complexes and causes endothelial damage. Drugs used to treat cancer have also been reported to produce Henoch-Schönlein purpura.⁴

Although hematologic malignancy is three to five times more common than solid tumors in patients with small-vessel vasculitis, the disease has been associated with solid tumors of the liver, skin, colon, and breast in adults over age 40.⁵ An evaluation for neoplasm is therefore reasonable in adults with Henoch-Schönlein purpura, as is an evaluation for tumor recurrence or metastasis if the patient has been previously treated for a malignant tumor.

A healthy 47-year-old woman presents with a 3-day history of widespread asymptomatic lesions in the extremities, fever, arthralgias, and mild abdominal pain. A physical examination reveals a symmetric rash in the lower legs with erythematous purple papules. These papules do not blanch when pressure is applied and so are clinically compatible with palpable purpura (Figure 1). Skin biopsy shows leukocytoclastic vasculitis with immunoglobulin A (IgA) deposits in the vascular wall.

Q: Which is the most likely diagnosis?

• Idiopathic thrombocytopenic purpura
• Vitamin C deficiency (scurvy)
• Kaposi sarcoma not related to human immunodeficiency virus (HIV) infection
• Henoch-Schönlein purpura
• Polyarteritis nodosa

A: The correct answer is Henoch-Schönlein purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disease caused by specific antibodies against platelet-membrane glycoproteins. It is characterized by thrombocytopenia not explainable by contact with toxic substances or by other causes. Along with nonpalpable purpura, other common signs are epistaxis, gingival bleeding, menorrhagia, and retinal hemorrhage.

Scurvy is an uncommon deficiency of ascorbic acid (vitamin C). The elderly and alcoholics are at higher risk, as they do not take in enough vitamin C in the diet. Patients usually show perifollicular hemorrhages of the skin and mucous membranes, typically petechial hemorrhage or ecchymosis of the gums around the upper incisors. Other cutaneous signs are follicular hyperkeratosis on the forearms, small corkscrew hairs, and sicca syndrome, which is more common in adults.

Non-HIV Kaposi sarcoma usually affects elderly patients, with pink, red, or brown papules or nodules on the legs and, less commonly, on the head and neck. Histopathologic examination shows newly formed irregular blood vessels with an inflammatory infiltrate of plasma cells and lymphocytes; immunohistochemical human herpes virus staining is usually positive.

Polyarteritis nodosa is a systemic vasculitis that affects medium or small arteries with necrotizing inflammation; renal glomeruli and arterioles, capillaries, and venules are unaffected. Skin manifestations include palpable purpura, livedo reticularis, ulcers, and distal gangrene. The condition also usually affects the kidneys, the heart, and the musculoskeletal and nervous systems.

 

A SYSTEMIC VASCULITIS

Henoch-Schönlein purpura is a systemic vasculitis affecting the skin, gastrointestinal tract, kidneys, and joints. Palpable purpura and joint pain are the most common and consistent presenting symptoms. The kidneys are affected in about one-third of children and in 60% of adults, and this is the major factor determining the long-term outcome.¹

In our patient, laboratory testing that included a complete blood cell count, biochemical testing (including IgA levels), urinary sediment, and coagulation studies showed no abnormalities except elevations of the erythrocyte sedimentation rate and the concentration of C-reactive protein (an acute-phase reactant). These can be normal in some patients. Renal involvement was also not present.

DIAGNOSIS

The diagnosis relies on clinical manifestations. Because Henoch-Schönlein purpura is less common in adults, biopsy plays a more important role in establishing the diagnosis in this age group, and it does this by demonstrating leukocytoclastic vasculitis with a predominance of IgA deposition under immunofluorescence. Recent studies in children showed that an elevated IgA concentration along with reduced IgM levels was associated with a higher rate of severe complications.² However, depending on the age of the biopsied lesion, IgA may not be detected.

TREATMENT DIRECTED AT SYMPTOMS

Our patient received oral corticosteroids 0.5 mg/kg per day for 20 days, and the lesions resolved by 4 weeks.

Management of Henoch-Schönlein purpura is mainly directed at the symptoms, with oral hydration and nonsteroidal anti-inflammatory drugs. For severe cases, a short course of corticosteroids (0.5–1 mg/kg) may be used.

Although no controlled clinical trial has proven that Henoch-Schönlein purpura responds to corticosteroids, colchicine, or other drugs, corticosteroids are used most often, especially in patients with renal disease. Patients with severe renal insufficiency, abdominal pain, joint involvement, or bleeding should be hospitalized. Plasmapheresis³ has been used in severe cases.

HENOCH-SCHÖNLEIN PURPURA AND MALIGNANCY

During a follow-up evaluation 1 month later, our patient was diagnosed with adenocarcinoma of the breast. This highlights the value of a workup for cancer in adults with cutaneous vasculitis.

Cutaneous vasculitis can represent a paraneoplastic syndrome associated with a malignant tumor. The pathophysiology of this association is unclear, but one proposed mechanism is the exaggerated production of antibodies that react against tumor neoantigens, leading to the formation of immune complexes, or that occasionally recognize endothelial cells because of similarities with tumor antigens. Another theory is that abnormally high levels of inflammatory cytokines are produced by neoplastic cells or in response to decreased immune complex clearance.

Yet another theory is that hyperviscosity of the blood, seen in some cancers, increases the contact time for deposition of immune complexes and causes endothelial damage. Drugs used to treat cancer have also been reported to produce Henoch-Schönlein purpura.⁴

Although hematologic malignancy is three to five times more common than solid tumors in patients with small-vessel vasculitis, the disease has been associated with solid tumors of the liver, skin, colon, and breast in adults over age 40.⁵ An evaluation for neoplasm is therefore reasonable in adults with Henoch-Schönlein purpura, as is an evaluation for tumor recurrence or metastasis if the patient has been previously treated for a malignant tumor.

A healthy 47-year-old woman presents with a 3-day history of widespread asymptomatic lesions in the extremities, fever, arthralgias, and mild abdominal pain. A physical examination reveals a symmetric rash in the lower legs with erythematous purple papules. These papules do not blanch when pressure is applied and so are clinically compatible with palpable purpura (Figure 1). Skin biopsy shows leukocytoclastic vasculitis with immunoglobulin A (IgA) deposits in the vascular wall.

Q: Which is the most likely diagnosis?

• Idiopathic thrombocytopenic purpura
• Vitamin C deficiency (scurvy)
• Kaposi sarcoma not related to human immunodeficiency virus (HIV) infection
• Henoch-Schönlein purpura
• Polyarteritis nodosa

A: The correct answer is Henoch-Schönlein purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disease caused by specific antibodies against platelet-membrane glycoproteins. It is characterized by thrombocytopenia not explainable by contact with toxic substances or by other causes. Along with nonpalpable purpura, other common signs are epistaxis, gingival bleeding, menorrhagia, and retinal hemorrhage.

Scurvy is an uncommon deficiency of ascorbic acid (vitamin C). The elderly and alcoholics are at higher risk, as they do not take in enough vitamin C in the diet. Patients usually show perifollicular hemorrhages of the skin and mucous membranes, typically petechial hemorrhage or ecchymosis of the gums around the upper incisors. Other cutaneous signs are follicular hyperkeratosis on the forearms, small corkscrew hairs, and sicca syndrome, which is more common in adults.

Non-HIV Kaposi sarcoma usually affects elderly patients, with pink, red, or brown papules or nodules on the legs and, less commonly, on the head and neck. Histopathologic examination shows newly formed irregular blood vessels with an inflammatory infiltrate of plasma cells and lymphocytes; immunohistochemical human herpes virus staining is usually positive.

Polyarteritis nodosa is a systemic vasculitis that affects medium or small arteries with necrotizing inflammation; renal glomeruli and arterioles, capillaries, and venules are unaffected. Skin manifestations include palpable purpura, livedo reticularis, ulcers, and distal gangrene. The condition also usually affects the kidneys, the heart, and the musculoskeletal and nervous systems.

 

A SYSTEMIC VASCULITIS

Henoch-Schönlein purpura is a systemic vasculitis affecting the skin, gastrointestinal tract, kidneys, and joints. Palpable purpura and joint pain are the most common and consistent presenting symptoms. The kidneys are affected in about one-third of children and in 60% of adults, and this is the major factor determining the long-term outcome.¹

In our patient, laboratory testing that included a complete blood cell count, biochemical testing (including IgA levels), urinary sediment, and coagulation studies showed no abnormalities except elevations of the erythrocyte sedimentation rate and the concentration of C-reactive protein (an acute-phase reactant). These can be normal in some patients. Renal involvement was also not present.

DIAGNOSIS

The diagnosis relies on clinical manifestations. Because Henoch-Schönlein purpura is less common in adults, biopsy plays a more important role in establishing the diagnosis in this age group, and it does this by demonstrating leukocytoclastic vasculitis with a predominance of IgA deposition under immunofluorescence. Recent studies in children showed that an elevated IgA concentration along with reduced IgM levels was associated with a higher rate of severe complications.² However, depending on the age of the biopsied lesion, IgA may not be detected.

TREATMENT DIRECTED AT SYMPTOMS

Our patient received oral corticosteroids 0.5 mg/kg per day for 20 days, and the lesions resolved by 4 weeks.

Management of Henoch-Schönlein purpura is mainly directed at the symptoms, with oral hydration and nonsteroidal anti-inflammatory drugs. For severe cases, a short course of corticosteroids (0.5–1 mg/kg) may be used.

Although no controlled clinical trial has proven that Henoch-Schönlein purpura responds to corticosteroids, colchicine, or other drugs, corticosteroids are used most often, especially in patients with renal disease. Patients with severe renal insufficiency, abdominal pain, joint involvement, or bleeding should be hospitalized. Plasmapheresis³ has been used in severe cases.

HENOCH-SCHÖNLEIN PURPURA AND MALIGNANCY

During a follow-up evaluation 1 month later, our patient was diagnosed with adenocarcinoma of the breast. This highlights the value of a workup for cancer in adults with cutaneous vasculitis.

Cutaneous vasculitis can represent a paraneoplastic syndrome associated with a malignant tumor. The pathophysiology of this association is unclear, but one proposed mechanism is the exaggerated production of antibodies that react against tumor neoantigens, leading to the formation of immune complexes, or that occasionally recognize endothelial cells because of similarities with tumor antigens. Another theory is that abnormally high levels of inflammatory cytokines are produced by neoplastic cells or in response to decreased immune complex clearance.

Yet another theory is that hyperviscosity of the blood, seen in some cancers, increases the contact time for deposition of immune complexes and causes endothelial damage. Drugs used to treat cancer have also been reported to produce Henoch-Schönlein purpura.⁴

Although hematologic malignancy is three to five times more common than solid tumors in patients with small-vessel vasculitis, the disease has been associated with solid tumors of the liver, skin, colon, and breast in adults over age 40.⁵ An evaluation for neoplasm is therefore reasonable in adults with Henoch-Schönlein purpura, as is an evaluation for tumor recurrence or metastasis if the patient has been previously treated for a malignant tumor.