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Large Subcutaneous Masses
The Diagnosis: Madelung Disease (Benign Symmetric Lipomatosis)
A 56-year-old man presented for evaluation of massive subcutaneous nodules the bilateral upper arms, shoulders, chest, abdomen, and lateral aspect of the proximal thighs (Figures 1 and 2) that developed over the last 12 to 18 months and continued to enlarge. In addition, he was beginning to develop symptoms of neuropathy of the bilateral hands. The patient had a long-standing history of alcohol abuse. Biopsies performed by the patient’s primary care physician revealed benign adipose tissue. He was referred to the dermatology clinic and subsequently diagnosed with Madelung disease.
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Madelung disease, also known as benign symmetric lipomatosis and Launois-Bensaude syndrome, is characterized by multiple large masses of nonencapsulated adipose tissue. These masses are symmetric and most prominent on the head, neck, trunk, and proximal extremities. Classically, a pseudoathletic appearance is described. Madelung disease most frequently affects men aged 30 to 60 years. In more than 90% of cases, it is associated with alcoholism.
In general, the masses of adipose tissue are asymptomatic. However, airway compression and dysphagia requiring surgical intervention has been reported in the otolaryngology literature.1 In addition, neuropathy develops in 84% of cases.2 Nerve biopsies from patients with Madelung disease have revealed a pattern of axonopathy that is distinct from alcohol-induced neuropathy.3 This neuropathy can involve sensory and motor nerves, with the most prominent findings being muscle weakness, tendon areflexia, interosseous muscle atrophy, vibratory sensation loss, and hypoesthesia. Furthermore, dysfunction of the autonomic nervous system can lead to segmental hyperhidrosis, gustatory sweating, and abnormal autonomic cardiovascular reflexes.2 Many patients who develop neuropathy will eventually become incapacitated.
The etiology of Madelung disease is not fully understood. There are several theories on the pathogenesis of this disease, most describing metabolic disturbances induced by alcohol. Specifically, studies have revealed chronic alcohol use causes numerous deletions in mitochondrial DNA.4,5 The mitochondrial DNA damage may explain both the resistance of the lipomatous masses to lipolysis and the nerve-related changes. Comparisons between human immunodeficiency virus/highly active antiretroviral therapy–associated lipodystrophy and Madelung disease lend credence to the metabolic disturbance theory and may help clarify the specific mechanisms involved.6
There have been no cases of spontaneous resolution, even in patients who stop consuming alcohol. For this reason, most patients are referred to a surgeon. Many surgeons prefer open excision for debulking large lipomatous masses, but this technique typically requires general anesthesia. For those in whom this treatment is not an appropriate option, liposuction can be considered with tumescent anesthesia.7 A combination of these surgical modalities also is an option.
Madelung disease is a distinctive disorder typically affecting chronic alcoholics. Recognition of this clinical entity is important, as severe neuropathy and airway compromise may ensue. Although surgical excision is an attractive option for cosmesis and airway compromise, the associated neuropathy can be extremely difficult to treat and can be quite debilitating.
1. Palacios E, Neitzschman HR, Nguyen J. Madelung disease: multiple symmetric lipomatosis. Ear Nose Throat J. 2014;93:94-96.
2. Enzi G, Angelini C, Negrin P, et al. Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis. Medicine (Baltimore). 1985;64:388-393.
3. Pollock M, Nicholson GI, Nukada H, et al. Neuropathy in multiple symmetric lipomatosis. Madelung’s disease. Brain. 1988;111:1157-1171.
4. Klopstock T, Naumann M, Schalke B, et al. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology. 1994;44:862-866.
5. Mansouri A, Fromenty B, Berson A, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96-102.
6. Urso R, Gentile M. Are ‘buffalo hump’ syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? AIDS. 2001;15:290-291.
7. Grassegger A, Häussler R, Schmalzl F. Tumescent liposuction in a patient with Launois-Bensaude syndrome and severe hepatopathy. Dermatol Surg. 2007;33:982-985.
The Diagnosis: Madelung Disease (Benign Symmetric Lipomatosis)
A 56-year-old man presented for evaluation of massive subcutaneous nodules the bilateral upper arms, shoulders, chest, abdomen, and lateral aspect of the proximal thighs (Figures 1 and 2) that developed over the last 12 to 18 months and continued to enlarge. In addition, he was beginning to develop symptoms of neuropathy of the bilateral hands. The patient had a long-standing history of alcohol abuse. Biopsies performed by the patient’s primary care physician revealed benign adipose tissue. He was referred to the dermatology clinic and subsequently diagnosed with Madelung disease.
|
|
Madelung disease, also known as benign symmetric lipomatosis and Launois-Bensaude syndrome, is characterized by multiple large masses of nonencapsulated adipose tissue. These masses are symmetric and most prominent on the head, neck, trunk, and proximal extremities. Classically, a pseudoathletic appearance is described. Madelung disease most frequently affects men aged 30 to 60 years. In more than 90% of cases, it is associated with alcoholism.
In general, the masses of adipose tissue are asymptomatic. However, airway compression and dysphagia requiring surgical intervention has been reported in the otolaryngology literature.1 In addition, neuropathy develops in 84% of cases.2 Nerve biopsies from patients with Madelung disease have revealed a pattern of axonopathy that is distinct from alcohol-induced neuropathy.3 This neuropathy can involve sensory and motor nerves, with the most prominent findings being muscle weakness, tendon areflexia, interosseous muscle atrophy, vibratory sensation loss, and hypoesthesia. Furthermore, dysfunction of the autonomic nervous system can lead to segmental hyperhidrosis, gustatory sweating, and abnormal autonomic cardiovascular reflexes.2 Many patients who develop neuropathy will eventually become incapacitated.
The etiology of Madelung disease is not fully understood. There are several theories on the pathogenesis of this disease, most describing metabolic disturbances induced by alcohol. Specifically, studies have revealed chronic alcohol use causes numerous deletions in mitochondrial DNA.4,5 The mitochondrial DNA damage may explain both the resistance of the lipomatous masses to lipolysis and the nerve-related changes. Comparisons between human immunodeficiency virus/highly active antiretroviral therapy–associated lipodystrophy and Madelung disease lend credence to the metabolic disturbance theory and may help clarify the specific mechanisms involved.6
There have been no cases of spontaneous resolution, even in patients who stop consuming alcohol. For this reason, most patients are referred to a surgeon. Many surgeons prefer open excision for debulking large lipomatous masses, but this technique typically requires general anesthesia. For those in whom this treatment is not an appropriate option, liposuction can be considered with tumescent anesthesia.7 A combination of these surgical modalities also is an option.
Madelung disease is a distinctive disorder typically affecting chronic alcoholics. Recognition of this clinical entity is important, as severe neuropathy and airway compromise may ensue. Although surgical excision is an attractive option for cosmesis and airway compromise, the associated neuropathy can be extremely difficult to treat and can be quite debilitating.
The Diagnosis: Madelung Disease (Benign Symmetric Lipomatosis)
A 56-year-old man presented for evaluation of massive subcutaneous nodules the bilateral upper arms, shoulders, chest, abdomen, and lateral aspect of the proximal thighs (Figures 1 and 2) that developed over the last 12 to 18 months and continued to enlarge. In addition, he was beginning to develop symptoms of neuropathy of the bilateral hands. The patient had a long-standing history of alcohol abuse. Biopsies performed by the patient’s primary care physician revealed benign adipose tissue. He was referred to the dermatology clinic and subsequently diagnosed with Madelung disease.
|
|
Madelung disease, also known as benign symmetric lipomatosis and Launois-Bensaude syndrome, is characterized by multiple large masses of nonencapsulated adipose tissue. These masses are symmetric and most prominent on the head, neck, trunk, and proximal extremities. Classically, a pseudoathletic appearance is described. Madelung disease most frequently affects men aged 30 to 60 years. In more than 90% of cases, it is associated with alcoholism.
In general, the masses of adipose tissue are asymptomatic. However, airway compression and dysphagia requiring surgical intervention has been reported in the otolaryngology literature.1 In addition, neuropathy develops in 84% of cases.2 Nerve biopsies from patients with Madelung disease have revealed a pattern of axonopathy that is distinct from alcohol-induced neuropathy.3 This neuropathy can involve sensory and motor nerves, with the most prominent findings being muscle weakness, tendon areflexia, interosseous muscle atrophy, vibratory sensation loss, and hypoesthesia. Furthermore, dysfunction of the autonomic nervous system can lead to segmental hyperhidrosis, gustatory sweating, and abnormal autonomic cardiovascular reflexes.2 Many patients who develop neuropathy will eventually become incapacitated.
The etiology of Madelung disease is not fully understood. There are several theories on the pathogenesis of this disease, most describing metabolic disturbances induced by alcohol. Specifically, studies have revealed chronic alcohol use causes numerous deletions in mitochondrial DNA.4,5 The mitochondrial DNA damage may explain both the resistance of the lipomatous masses to lipolysis and the nerve-related changes. Comparisons between human immunodeficiency virus/highly active antiretroviral therapy–associated lipodystrophy and Madelung disease lend credence to the metabolic disturbance theory and may help clarify the specific mechanisms involved.6
There have been no cases of spontaneous resolution, even in patients who stop consuming alcohol. For this reason, most patients are referred to a surgeon. Many surgeons prefer open excision for debulking large lipomatous masses, but this technique typically requires general anesthesia. For those in whom this treatment is not an appropriate option, liposuction can be considered with tumescent anesthesia.7 A combination of these surgical modalities also is an option.
Madelung disease is a distinctive disorder typically affecting chronic alcoholics. Recognition of this clinical entity is important, as severe neuropathy and airway compromise may ensue. Although surgical excision is an attractive option for cosmesis and airway compromise, the associated neuropathy can be extremely difficult to treat and can be quite debilitating.
1. Palacios E, Neitzschman HR, Nguyen J. Madelung disease: multiple symmetric lipomatosis. Ear Nose Throat J. 2014;93:94-96.
2. Enzi G, Angelini C, Negrin P, et al. Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis. Medicine (Baltimore). 1985;64:388-393.
3. Pollock M, Nicholson GI, Nukada H, et al. Neuropathy in multiple symmetric lipomatosis. Madelung’s disease. Brain. 1988;111:1157-1171.
4. Klopstock T, Naumann M, Schalke B, et al. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology. 1994;44:862-866.
5. Mansouri A, Fromenty B, Berson A, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96-102.
6. Urso R, Gentile M. Are ‘buffalo hump’ syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? AIDS. 2001;15:290-291.
7. Grassegger A, Häussler R, Schmalzl F. Tumescent liposuction in a patient with Launois-Bensaude syndrome and severe hepatopathy. Dermatol Surg. 2007;33:982-985.
1. Palacios E, Neitzschman HR, Nguyen J. Madelung disease: multiple symmetric lipomatosis. Ear Nose Throat J. 2014;93:94-96.
2. Enzi G, Angelini C, Negrin P, et al. Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis. Medicine (Baltimore). 1985;64:388-393.
3. Pollock M, Nicholson GI, Nukada H, et al. Neuropathy in multiple symmetric lipomatosis. Madelung’s disease. Brain. 1988;111:1157-1171.
4. Klopstock T, Naumann M, Schalke B, et al. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology. 1994;44:862-866.
5. Mansouri A, Fromenty B, Berson A, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96-102.
6. Urso R, Gentile M. Are ‘buffalo hump’ syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? AIDS. 2001;15:290-291.
7. Grassegger A, Häussler R, Schmalzl F. Tumescent liposuction in a patient with Launois-Bensaude syndrome and severe hepatopathy. Dermatol Surg. 2007;33:982-985.
A 56-year-old man presented for evaluation of massive subcutaneous nodules on the bilateral upper arms, shoulders, chest, abdomen, and lateral aspect of the proximal thighs that developed over the last 12 to 18 months and continued to enlarge. His medical history was remarkable for alcoholism, hyperlipidemia, and hypertension.
Cutaneous Manifestations of Cocaine Use
The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy
In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).
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Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.1 Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.
Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.2 Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.3
Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)4; oral mucosal involvement also has been reported.5 Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.4 Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.6 On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.
|
Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.7 Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.8
Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).9 Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.9
Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.1 Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.10 Oral prednisone and colchicine also have been used with reported success.5
Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.
1. Aberastury MN, Silva WH, Vaccarezza MM, et al. Epilepsia partialis continua associated with levamisole. Pediatr Neurol. 2011;44:385-388.
2. Nationwide public health alert issued concerning life-threatening risk posed by cocaine laced with veterinary anti-parasite drug [press release]. Rockville, MD: Substance Abuse and Mental Health Services Administration; September 21, 2009. http://beta.samhsa.gov/newsroom/press-announcements/200909211245. Accessed October 9, 2014.
3. Lee KC, Culpepper K, Kessler M. Levamisole-induced thrombosis: literature review and pertinent laboratory findings. J Am Acad Dermatol. 2011;65:e128-e129.
4. McGrath MM, Isakova T, Rennke HG, et al. Contaminated cocaine and antineutrophil cytoplasm antibody-associated disease. Clin J Am Soc Nephrol. 2011;6:2799-2805.
5. Poon SH, Baliog CR Jr, Sams RN, et al. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leucopenia. Semin Arthritis Rheum. 2011;41:434-444.
6. Walsh NM, Green PJ, Burlingame RW, et al. Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole. J Cutan Pathol. 2010;37:1212-1219.
7. Buchanan JA, Heard K, Burbach C, et al. Prevalence of levamisole in urine toxicology screens positive for cocaine in an inner-city hospital. JAMA. 2011;305:1657-1658.
8. Trehy ML, Brown DJ, Woodruff JT, et al. Determination of levamisole in urine by gas chromatography-mass spectrometry. J Anal Toxicol. 2001;35:545-550.
9. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012;87:581-586.
10. Zhu NY, Legatt DF, Turner AR. Agranulocytosis after consumption of cocaine adulterated with levamisole. Ann Intern Med. 2009;150:287-289.
The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy
In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).
|
Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.1 Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.
Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.2 Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.3
Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)4; oral mucosal involvement also has been reported.5 Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.4 Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.6 On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.
|
Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.7 Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.8
Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).9 Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.9
Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.1 Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.10 Oral prednisone and colchicine also have been used with reported success.5
Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.
The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy
In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).
|
Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.1 Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.
Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.2 Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.3
Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)4; oral mucosal involvement also has been reported.5 Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.4 Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.6 On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.
|
Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.7 Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.8
Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).9 Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.9
Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.1 Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.10 Oral prednisone and colchicine also have been used with reported success.5
Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.
1. Aberastury MN, Silva WH, Vaccarezza MM, et al. Epilepsia partialis continua associated with levamisole. Pediatr Neurol. 2011;44:385-388.
2. Nationwide public health alert issued concerning life-threatening risk posed by cocaine laced with veterinary anti-parasite drug [press release]. Rockville, MD: Substance Abuse and Mental Health Services Administration; September 21, 2009. http://beta.samhsa.gov/newsroom/press-announcements/200909211245. Accessed October 9, 2014.
3. Lee KC, Culpepper K, Kessler M. Levamisole-induced thrombosis: literature review and pertinent laboratory findings. J Am Acad Dermatol. 2011;65:e128-e129.
4. McGrath MM, Isakova T, Rennke HG, et al. Contaminated cocaine and antineutrophil cytoplasm antibody-associated disease. Clin J Am Soc Nephrol. 2011;6:2799-2805.
5. Poon SH, Baliog CR Jr, Sams RN, et al. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leucopenia. Semin Arthritis Rheum. 2011;41:434-444.
6. Walsh NM, Green PJ, Burlingame RW, et al. Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole. J Cutan Pathol. 2010;37:1212-1219.
7. Buchanan JA, Heard K, Burbach C, et al. Prevalence of levamisole in urine toxicology screens positive for cocaine in an inner-city hospital. JAMA. 2011;305:1657-1658.
8. Trehy ML, Brown DJ, Woodruff JT, et al. Determination of levamisole in urine by gas chromatography-mass spectrometry. J Anal Toxicol. 2001;35:545-550.
9. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012;87:581-586.
10. Zhu NY, Legatt DF, Turner AR. Agranulocytosis after consumption of cocaine adulterated with levamisole. Ann Intern Med. 2009;150:287-289.
1. Aberastury MN, Silva WH, Vaccarezza MM, et al. Epilepsia partialis continua associated with levamisole. Pediatr Neurol. 2011;44:385-388.
2. Nationwide public health alert issued concerning life-threatening risk posed by cocaine laced with veterinary anti-parasite drug [press release]. Rockville, MD: Substance Abuse and Mental Health Services Administration; September 21, 2009. http://beta.samhsa.gov/newsroom/press-announcements/200909211245. Accessed October 9, 2014.
3. Lee KC, Culpepper K, Kessler M. Levamisole-induced thrombosis: literature review and pertinent laboratory findings. J Am Acad Dermatol. 2011;65:e128-e129.
4. McGrath MM, Isakova T, Rennke HG, et al. Contaminated cocaine and antineutrophil cytoplasm antibody-associated disease. Clin J Am Soc Nephrol. 2011;6:2799-2805.
5. Poon SH, Baliog CR Jr, Sams RN, et al. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leucopenia. Semin Arthritis Rheum. 2011;41:434-444.
6. Walsh NM, Green PJ, Burlingame RW, et al. Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole. J Cutan Pathol. 2010;37:1212-1219.
7. Buchanan JA, Heard K, Burbach C, et al. Prevalence of levamisole in urine toxicology screens positive for cocaine in an inner-city hospital. JAMA. 2011;305:1657-1658.
8. Trehy ML, Brown DJ, Woodruff JT, et al. Determination of levamisole in urine by gas chromatography-mass spectrometry. J Anal Toxicol. 2001;35:545-550.
9. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012;87:581-586.
10. Zhu NY, Legatt DF, Turner AR. Agranulocytosis after consumption of cocaine adulterated with levamisole. Ann Intern Med. 2009;150:287-289.
A 43-year-old woman presented to the emergency department with painful skin lesions of 1 day’s duration. Physical examination revealed tender stellate purpura and occasional bullae on the ears, arms and legs, groin, and buttocks. Laboratory results revealed neutropenia and positive lupus anticoagulant; antineutrophil cytoplasmic antibody, antinuclear antibody, and double-stranded DNA antibodies were all negative. Urine toxicology was positive for cocaine and opioids. An incisional biopsy of the left arm was performed.
Fatal Family History Worries Young Man
ANSWER
The ECG shows normal sinus rhythm and left ventricular hypertrophy (LVH). LVH is indicated by high voltages in limb leads I and III (sum of R and S waves in leads I and III ≥ 25 mm) or in precordial leads V1, V5, and/or V6 (sum of V1 and either V5 or V6 ≥ 35 mm).
Subsequent work-up, including echocardiography and genetic testing, revealed a familial LVH.
ANSWER
The ECG shows normal sinus rhythm and left ventricular hypertrophy (LVH). LVH is indicated by high voltages in limb leads I and III (sum of R and S waves in leads I and III ≥ 25 mm) or in precordial leads V1, V5, and/or V6 (sum of V1 and either V5 or V6 ≥ 35 mm).
Subsequent work-up, including echocardiography and genetic testing, revealed a familial LVH.
ANSWER
The ECG shows normal sinus rhythm and left ventricular hypertrophy (LVH). LVH is indicated by high voltages in limb leads I and III (sum of R and S waves in leads I and III ≥ 25 mm) or in precordial leads V1, V5, and/or V6 (sum of V1 and either V5 or V6 ≥ 35 mm).
Subsequent work-up, including echocardiography and genetic testing, revealed a familial LVH.
A college student, 19, presents with increasing palpitations. Six months ago, when they began, they were rare and intermittent; now they occur daily, primarily at night. He has just received an athletic scholarship and worries that the palpitations may affect his ability to play. Furthermore, his older brother died of sudden cardiac death in high school, while playing football, and the patient is afraid this may happen to him too. He is in otherwise excellent health and has never been hospitalized. He takes no medications but has smoked marijuana a couple of times. He has not used performance enhancing drugs or homeopathic medications. A careful review of his family history reveals that two uncles, a brother, and a cousin died of sudden cardiac death. Their ages at the time of death were 42, 51, 17, and 54, respectively. Review of systems is unremarkable. Vital signs include a blood pressure of 108/62 mm Hg; pulse, 60 beats/min; and respiratory rate, 14 breaths/min-1. His weight is 179 lb and his height, 78 in. The physical exam reveals a tall, thin, well-developed young male in no distress. A comprehensive examination reveals no adverse findings. There are no palpitations heard or felt. Despite the lack of unusual physical findings, the patient’s family history concerns you. You decide to order an ECG and an echocardiogram. The ECG shows a ventricular rate of 61 beats/min; PR interval, 120 ms; QRS duration, 108 ms; QT/QTc interval, 430/432 ms; P axis, –25°; R axis, –14°; and T axis, 12°. What is your interpretation of this ECG—and is further work-up indicated?
Retired Tour Guide Intends to Maintain Her Tan
ANSWER
The correct answer is poikiloderma of Civatte (choice “c”), details of which are discussed below.
Poikiloderma vasculare atrophicans (choice “a”) can be an early indication of T-cell lymphoma but would probably not be chronic or confined to sun-exposed skin.
Several forms of lupus (choice “b”) can present with poikilodermatous skin changes, but these would probably not be chronic.
Dermatoheliosis (choice “d”) is the term for the collective effects of overexposure to the sun, of which poikiloderma of Civatte is but one example.
DISCUSSION
The French dermatologist Achille Civatte (1877-1956) first described this particular pattern of sun damage in 1923—about the same time that sunbathing became fashionable among the well-off in the post-WWI era. He noted the distinct combination of telangiectasias, hyperpigmentation, and epidermal atrophy affecting the bilateral neck and lower face, combined with sharply defined sparing of the portion of the anterior neck shaded by the chin. Poikiloderma of Civatte (PC) is extremely common, especially in middle-aged women and, as one might expect, in those with a history of excessive sun exposure over a period of many years.
Though sun-caused, PC is a purely cosmetic issue and does not lead to skin cancer. While it typically causes no symptoms, it does become more obvious with time. The changes are so gradual that others typically notice them before the patient becomes aware.
Transposing these types of skin changes to other locations would make them considerably more worrisome, specifically in the context of possible incipient T-cell lymphoma—one of the very few types of skin cancer that can take years to evolve into frank cancer. But the atrophy, telangiectasias, and discoloration signaling early cutaneous T-cell lymphoma are usually seen in non–sun-exposed skin, particularly in the waistline and groin.
Poikiloderma vasculare atrophicans is only one of several manifestations termed premycotic. This refers to mycosis fungoides, one of the two most common forms of T-cell lymphoma. Serial biopsy, sometimes over the span of several years, is often used to track such changes.
Pulsed light devices and certain types of lasers have been used successfully to treat PC. Our patient, however, declined treatment, declaring her firm intention to maintain “a healthy tan” year-round.
ANSWER
The correct answer is poikiloderma of Civatte (choice “c”), details of which are discussed below.
Poikiloderma vasculare atrophicans (choice “a”) can be an early indication of T-cell lymphoma but would probably not be chronic or confined to sun-exposed skin.
Several forms of lupus (choice “b”) can present with poikilodermatous skin changes, but these would probably not be chronic.
Dermatoheliosis (choice “d”) is the term for the collective effects of overexposure to the sun, of which poikiloderma of Civatte is but one example.
DISCUSSION
The French dermatologist Achille Civatte (1877-1956) first described this particular pattern of sun damage in 1923—about the same time that sunbathing became fashionable among the well-off in the post-WWI era. He noted the distinct combination of telangiectasias, hyperpigmentation, and epidermal atrophy affecting the bilateral neck and lower face, combined with sharply defined sparing of the portion of the anterior neck shaded by the chin. Poikiloderma of Civatte (PC) is extremely common, especially in middle-aged women and, as one might expect, in those with a history of excessive sun exposure over a period of many years.
Though sun-caused, PC is a purely cosmetic issue and does not lead to skin cancer. While it typically causes no symptoms, it does become more obvious with time. The changes are so gradual that others typically notice them before the patient becomes aware.
Transposing these types of skin changes to other locations would make them considerably more worrisome, specifically in the context of possible incipient T-cell lymphoma—one of the very few types of skin cancer that can take years to evolve into frank cancer. But the atrophy, telangiectasias, and discoloration signaling early cutaneous T-cell lymphoma are usually seen in non–sun-exposed skin, particularly in the waistline and groin.
Poikiloderma vasculare atrophicans is only one of several manifestations termed premycotic. This refers to mycosis fungoides, one of the two most common forms of T-cell lymphoma. Serial biopsy, sometimes over the span of several years, is often used to track such changes.
Pulsed light devices and certain types of lasers have been used successfully to treat PC. Our patient, however, declined treatment, declaring her firm intention to maintain “a healthy tan” year-round.
ANSWER
The correct answer is poikiloderma of Civatte (choice “c”), details of which are discussed below.
Poikiloderma vasculare atrophicans (choice “a”) can be an early indication of T-cell lymphoma but would probably not be chronic or confined to sun-exposed skin.
Several forms of lupus (choice “b”) can present with poikilodermatous skin changes, but these would probably not be chronic.
Dermatoheliosis (choice “d”) is the term for the collective effects of overexposure to the sun, of which poikiloderma of Civatte is but one example.
DISCUSSION
The French dermatologist Achille Civatte (1877-1956) first described this particular pattern of sun damage in 1923—about the same time that sunbathing became fashionable among the well-off in the post-WWI era. He noted the distinct combination of telangiectasias, hyperpigmentation, and epidermal atrophy affecting the bilateral neck and lower face, combined with sharply defined sparing of the portion of the anterior neck shaded by the chin. Poikiloderma of Civatte (PC) is extremely common, especially in middle-aged women and, as one might expect, in those with a history of excessive sun exposure over a period of many years.
Though sun-caused, PC is a purely cosmetic issue and does not lead to skin cancer. While it typically causes no symptoms, it does become more obvious with time. The changes are so gradual that others typically notice them before the patient becomes aware.
Transposing these types of skin changes to other locations would make them considerably more worrisome, specifically in the context of possible incipient T-cell lymphoma—one of the very few types of skin cancer that can take years to evolve into frank cancer. But the atrophy, telangiectasias, and discoloration signaling early cutaneous T-cell lymphoma are usually seen in non–sun-exposed skin, particularly in the waistline and groin.
Poikiloderma vasculare atrophicans is only one of several manifestations termed premycotic. This refers to mycosis fungoides, one of the two most common forms of T-cell lymphoma. Serial biopsy, sometimes over the span of several years, is often used to track such changes.
Pulsed light devices and certain types of lasers have been used successfully to treat PC. Our patient, however, declined treatment, declaring her firm intention to maintain “a healthy tan” year-round.
A 60-year-old woman is seen for complaints of skin changes on her neck that have slowly become more noticeable over a period of years. Although asymptomatic, these changes have been observed by others, who brought them to the patient’s attention. The patient worked as a tour guide in Arizona for 20 years, leading groups along desert trails to view native flora and fauna. During that time, she maintained a dark tan almost year-round, tanning easily and never using sunscreen. The patient has type III skin, bluish gray eyes, and light brown hair. Dark brown–to–red mottled pigmentary changes are seen on the sides of her neck; the central portion of the anterior neck is sharply spared. On closer inspection, many fine telangiectasias are noted in these same areas, as well as on the sun-exposed areas of the face. Aside from her skin changes, the patient claims to be quite healthy, with no joint pain, fever, or malaise.
More to the Story Than a Skull Fracture
ANSWER
The radiograph shows two areas of concern: Within the apex of the right lung, there is a vague haziness that, in the setting of trauma, is suggestive of a contusion or even aspiration pneumonia. Another possibility is some sort of neoplasm. In addition, the patient has what appears to be a rounded density within the left lung, also suspicious for neoplasm. Additional work-up with contrast-enhanced CT is warranted.
Through further questioning, the patient denies any current symptoms or previous/recent diagnosis of cancer. CT of the chest confirmed the presence of masses in the right upper and left lower lobes. Subsequent biopsy was consistent with a moderate to poorly differentiated squamous cell carcinoma.
ANSWER
The radiograph shows two areas of concern: Within the apex of the right lung, there is a vague haziness that, in the setting of trauma, is suggestive of a contusion or even aspiration pneumonia. Another possibility is some sort of neoplasm. In addition, the patient has what appears to be a rounded density within the left lung, also suspicious for neoplasm. Additional work-up with contrast-enhanced CT is warranted.
Through further questioning, the patient denies any current symptoms or previous/recent diagnosis of cancer. CT of the chest confirmed the presence of masses in the right upper and left lower lobes. Subsequent biopsy was consistent with a moderate to poorly differentiated squamous cell carcinoma.
ANSWER
The radiograph shows two areas of concern: Within the apex of the right lung, there is a vague haziness that, in the setting of trauma, is suggestive of a contusion or even aspiration pneumonia. Another possibility is some sort of neoplasm. In addition, the patient has what appears to be a rounded density within the left lung, also suspicious for neoplasm. Additional work-up with contrast-enhanced CT is warranted.
Through further questioning, the patient denies any current symptoms or previous/recent diagnosis of cancer. CT of the chest confirmed the presence of masses in the right upper and left lower lobes. Subsequent biopsy was consistent with a moderate to poorly differentiated squamous cell carcinoma.
A 63-year-old man is transferred to your facility with a skull fracture secondary to a fall. He thinks he tripped and fell, hitting his head. He does not recall experiencing dizziness or syncope. He states he was momentarily dazed but does not think he lost consciousness. He is complaining of a mild headache and has reported drainage from his left ear. He denies any noteworthy medical history and takes no medications regularly. He admits to smoking one to one-and-a-half packs of cigarettes per day. Initial assessment reveals an older-appearing male who is awake, alert, oriented, and in no obvious distress. His vital signs, including O2 saturation, are normal. His pupils are equal and react briskly. He does have obvious otorrhea from his left ear. He is moving all his extremities well and appears to have no deficits. You review his imaging studies, which include a chest radiograph (shown). What is your impression?
Hairs With an Irregular Shape
The Diagnosis: Circle Hairs
The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.
Circle hairs were first described in 1963.1 These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.2 Others propose that they are vestigial remains that once had a part in preserving body heat.3 Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.2,4
It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.2 If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.
 |
 |
| Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40). |
1. Adatto R. Poils en spirale (poils enroules). Dermatologica. 1963;127:145-147.
2. Smith JB, Hogan DJ. Circle hairs are not rolled hairs. J Am Acad Dermatol. 1996;35:634-635.
3. Contreras-Ruiz J, Duran-McKinster C, Tamayo-Sanchez L, et al. Circle hairs: a clinical curiosity. J Eur Acad Dermatol Venereol. 2000;14:495-497.
4. Levit F, Scott MJ Jr. Circle hairs. J Am Acad Dermatol. 1983;8:423-425.
The Diagnosis: Circle Hairs
The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.
Circle hairs were first described in 1963.1 These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.2 Others propose that they are vestigial remains that once had a part in preserving body heat.3 Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.2,4
It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.2 If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.
|
|
| Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40). |
The Diagnosis: Circle Hairs
The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.
Circle hairs were first described in 1963.1 These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.2 Others propose that they are vestigial remains that once had a part in preserving body heat.3 Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.2,4
It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.2 If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.
|
|
| Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40). |
1. Adatto R. Poils en spirale (poils enroules). Dermatologica. 1963;127:145-147.
2. Smith JB, Hogan DJ. Circle hairs are not rolled hairs. J Am Acad Dermatol. 1996;35:634-635.
3. Contreras-Ruiz J, Duran-McKinster C, Tamayo-Sanchez L, et al. Circle hairs: a clinical curiosity. J Eur Acad Dermatol Venereol. 2000;14:495-497.
4. Levit F, Scott MJ Jr. Circle hairs. J Am Acad Dermatol. 1983;8:423-425.
1. Adatto R. Poils en spirale (poils enroules). Dermatologica. 1963;127:145-147.
2. Smith JB, Hogan DJ. Circle hairs are not rolled hairs. J Am Acad Dermatol. 1996;35:634-635.
3. Contreras-Ruiz J, Duran-McKinster C, Tamayo-Sanchez L, et al. Circle hairs: a clinical curiosity. J Eur Acad Dermatol Venereol. 2000;14:495-497.
4. Levit F, Scott MJ Jr. Circle hairs. J Am Acad Dermatol. 1983;8:423-425.
A 74-year-old man was evaluated for numerous peculiar hairs on the back that had been present for several years. He reported no other dermatologic concerns. The patient was obese and led a sedentary lifestyle, spending most of the day sitting or lying down. Physical examination revealed a hairy back with many irregularly shaped hairs.
Hypopigmented Facial Papules on the Cheeks
The Diagnosis: Tumor of the Follicular Infundibulum
Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).
  Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100). |
Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5
There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.
Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.
1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.
2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.
4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.
5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.
6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.
7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.
8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.
The Diagnosis: Tumor of the Follicular Infundibulum
Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).
Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100). |
Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5
There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.
Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.
The Diagnosis: Tumor of the Follicular Infundibulum
Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).
Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100). |
Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5
There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.
Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.
1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.
2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.
4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.
5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.
6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.
7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.
8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.
1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.
2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.
4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.
5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.
6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.
7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.
8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.
A 73-year-old woman presented with multiple mildly pruritic, hypopigmented, thin papules involving both cheeks of 5 months’ duration. The patient had no improvement with ketoconazole cream 2% and hydrocortisone cream 1% used daily for 1 month for presumed tinea versicolor. Physical examination revealed 10 ill-defined, 2- to 5-mm, round and oval, smooth hypopigmented, slightly raised papules located on the lower aspect of both cheeks.
Confusion Follows Malaise and Pain
ANSWER
The radiograph demonstrates innumerable small lytic defects throughout the calvarium. The patient’s confusion is most likely secondary to profound metabolic abnormalities. However, in the setting of lytic bone lesions, metabolic abnormalities of renal insufficiency, severe hypercalcemia, and hypomagnesemia, one must be concerned about an occult myeloma, and appropriate work-up must be done.
ANSWER
The radiograph demonstrates innumerable small lytic defects throughout the calvarium. The patient’s confusion is most likely secondary to profound metabolic abnormalities. However, in the setting of lytic bone lesions, metabolic abnormalities of renal insufficiency, severe hypercalcemia, and hypomagnesemia, one must be concerned about an occult myeloma, and appropriate work-up must be done.
ANSWER
The radiograph demonstrates innumerable small lytic defects throughout the calvarium. The patient’s confusion is most likely secondary to profound metabolic abnormalities. However, in the setting of lytic bone lesions, metabolic abnormalities of renal insufficiency, severe hypercalcemia, and hypomagnesemia, one must be concerned about an occult myeloma, and appropriate work-up must be done.
A 70-year-old woman is brought to the emergency department by her family for evaluation of acute altered mental status. According to the family, the patient has been complaining of general malaise, back pain, and severe joint pain for the past few days. Her confusion has increased in the past 24 hours. Medical history is significant for hypertension. Physical exam reveals an elderly female who appears somewhat uncomfortable. Vital signs are normal. Overall, her exam is stable. She has tenderness throughout her back and several of her joints, but no abnormal effusion or swelling is noted. While the patient is in triage, baseline labwork is ordered. The results indicate a serum creatinine of 1.83 mg/dL; serum calcium, 16.7 mg/dL; and serum magnesium, 1.4 mEq/L. Radiograph of the skull is obtained. What is your impression?
During Veggie Harvest, Chest Pain Hits
ANSWER
This ECG is representative of an acute anterior MI. This is evidenced by ST segment elevation in leads V2 through V4. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as in leads V5 and V6.
Infarction was confirmed via laboratory data. Subsequent cardiac catheterization documented occlusion of the proximal left anterior descending artery.
ANSWER
This ECG is representative of an acute anterior MI. This is evidenced by ST segment elevation in leads V2 through V4. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as in leads V5 and V6.
Infarction was confirmed via laboratory data. Subsequent cardiac catheterization documented occlusion of the proximal left anterior descending artery.
ANSWER
This ECG is representative of an acute anterior MI. This is evidenced by ST segment elevation in leads V2 through V4. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as in leads V5 and V6.
Infarction was confirmed via laboratory data. Subsequent cardiac catheterization documented occlusion of the proximal left anterior descending artery.
A 48-year-old man arrives at your facility via emergency medical service (EMS). He is alert, oriented, and cooperative but reports substernal chest pain despite receiving two nitroglycerin tablets from the paramedics. The problem started while the patient was working in his garden, harvesting tomatoes and peppers but not doing anything particularly strenuous. The abrupt onset of chest pain caused him to stand up to catch his breath; he immediately became diaphoretic. The pain rated 10 out of 10 in severity and made him feel as if he’d been stabbed in the chest. After 10 minutes of persistent pain, he called to his neighbor, who contacted 911. The EMS arrived within six minutes. The paramedics found the patient conscious, profusely diaphoretic, and in severe pain; he was clutching his chest with his right fist. IV access was obtained, oxygen started, and sublingual nitroglycerin and aspirin given. The patient declined morphine due to a previous anaphylactic reaction to it. The pain subsided significantly, and the patient was loaded for transfer. During the 17-minute trip, his chest pain increased, and a second nitroglycerin tablet was given. It provided less relief than the previous one had. Medical history is remarkable for hypertension, smoking, adult-onset diabetes, and morbid obesity. The man has a primary care provider but hasn’t been seen in six years. He admits he is noncompliant with his medications because he just doesn’t like to take drugs—in fact, he hasn’t taken any of his prescribed medications for the past two years. He has never had chest pain prior to this event. Surgical history is remarkable for a cholecystectomy and a right knee replacement. His (unfilled) prescribed medications include a b-blocker, metformin, and a calcium channel blocker. He is allergic to morphine sulfate. He smokes marijuana on a daily basis because it calms his nerves. Review of systems is remarkable for multiple ulcers on the patient’s legs. He says he doesn’t require a cane for ambulation but prefers to walk with one. He also describes himself as a “nervous worrier,” hence his use of marijuana. Physical examination reveals an alert, anxious, and apprehensive man. His weight is 342 lb and his height, 70 in. He is afebrile and diaphoretic. Vital signs include a blood pressure of 164/98 mm Hg; pulse, 80 beats/min; respiratory rate, 20 breaths/min-1; and temperature, 97.4°F. Pertinent physical findings include no evidence of jugular venous distention or thyromegaly, clear lung sounds bilaterally, a regular rate and rhythm with distant muffled heart sounds, and no extra heart sounds or murmurs. The abdomen is obese, soft, and nontender. The peripheral pulses are equal bilaterally, and there is 2+ pitting edema present to the level of the knees. Multiple shallow ulcers are present on both lower legs, and a deep ulcer is present on the inferior surface of the left foot. After the patient is attached to telemetry monitoring and blood samples are drawn for analysis, an ECG is obtained. It reveals a ventricular rate of 80 beats/min; PR interval, 162 ms; QRS duration, 106 ms; QT/QTc interval, 370/426 ms; P axis, 51°; R axis, –20°; and T axis, 70°. What is your interpretation of this ECG?
Is It Ringworm, Herpes— Or Something Else Entirely?
ANSWER
The correct answer is impetigo (choice “c”), a superficial infection usually caused by a combination of staph and strep organisms.
Psoriasis (choice “a”) would have presented with white, tenacious scaling and would not have been acute in onset.
Eczema (choice “b”) is definitely possible, but the patient’s rash has features not seen with this condition; see Discussion for details.
Fungal infection (choice “d”) is also definitely in the differential, but it is unlikely given the negative KOH, the lack of any source for such infection, and the complete lack of response to tolnaftate cream.
DISCUSSION
Impetigo has also been called impetiginized dermatitis because it almost always starts with minor breaks in the skin as a result of conditions such as eczema, acne, contact dermatitis, or insect bite. Thus provided with access to deeper portions of the epithelial surface, bacterial organisms that normally cause no problems on intact skin are able to create a minor but annoying condition we have come to call impetigo.
Mistakenly called infantigo in large parts of the United States, impetigo is quite common but nonetheless alarming. Rarely associated with morbidity, it tends to resolve in two to three weeks at most, even without treatment.
Impetigo has the reputation of being highly contagious; given enough heat and humidity, close living conditions, and lack of regular bathing and/or adequate treatment, it can spread rapidly. Those conditions existed commonly 100 years ago, when bathing was sporadic and often cursory, and multiple family members lived and slept in close quarters. In those days before the introduction of antibiotics, there were no good topical antimicrobial agents, either.
Another factor played a major role in impetigo, bolstering its fearsome reputation. The strains of strep (group A b-hemolytic strep) that caused most impetigo in those days included several so-called nephritogenic strains that could lead to a dreaded complication: acute poststreptococcal glomerulonephritis (APSGN). Also called Bright disease, it could and did lead to fatal renal failure—about which little could be done at the time.
Fortunately, such nephritogenic strains of strep are unusual now, with APSGN occurring at a rate of about 1:1,000,000 in developed countries. In those locations, most people live far different lives today, bathing and changing clothes daily and living in much less cramped quarters.
The patient’s atopy likely had an impact, for several reasons: Since staph colonization of atopic persons is quite common, it’s more likely that an infection will develop. Also, thinner skin that is easily broken, a plethora of complicating problems (eg, dry skin, eczema, contact dermatitis, and exaggerated reactions to insect bites), and a lower threshold for itching all make atopic persons more susceptible to infection.
Most likely, our patient had a touch of eczema or dry skin and scratched it. Then, as the condition progressed, she scratched it more. The peroxide she used would have been highly irritating, serving only to worsen matters.
From a diagnostic point of view, the honey-colored crust covering the lesion and the context in which it developed led to a provisional diagnosis of impetiginized dermatitis. She was treated with oral cephalexin (500 mg tid for 7 d), topical mupirocin (applied bid), and topical hydrocortisone cream 2.5% (daily application). At one week’s follow-up, the patient’s skin was almost totally clear. It’s very unlikely she’ll have any residual scarring or blemish.
Had the diagnosis been unclear, or had the patient not responded to treatment, other diagnoses would have been considered. Among them: discoid lupus, psoriasis, contact dermatitis, and Darier disease.
ANSWER
The correct answer is impetigo (choice “c”), a superficial infection usually caused by a combination of staph and strep organisms.
Psoriasis (choice “a”) would have presented with white, tenacious scaling and would not have been acute in onset.
Eczema (choice “b”) is definitely possible, but the patient’s rash has features not seen with this condition; see Discussion for details.
Fungal infection (choice “d”) is also definitely in the differential, but it is unlikely given the negative KOH, the lack of any source for such infection, and the complete lack of response to tolnaftate cream.
DISCUSSION
Impetigo has also been called impetiginized dermatitis because it almost always starts with minor breaks in the skin as a result of conditions such as eczema, acne, contact dermatitis, or insect bite. Thus provided with access to deeper portions of the epithelial surface, bacterial organisms that normally cause no problems on intact skin are able to create a minor but annoying condition we have come to call impetigo.
Mistakenly called infantigo in large parts of the United States, impetigo is quite common but nonetheless alarming. Rarely associated with morbidity, it tends to resolve in two to three weeks at most, even without treatment.
Impetigo has the reputation of being highly contagious; given enough heat and humidity, close living conditions, and lack of regular bathing and/or adequate treatment, it can spread rapidly. Those conditions existed commonly 100 years ago, when bathing was sporadic and often cursory, and multiple family members lived and slept in close quarters. In those days before the introduction of antibiotics, there were no good topical antimicrobial agents, either.
Another factor played a major role in impetigo, bolstering its fearsome reputation. The strains of strep (group A b-hemolytic strep) that caused most impetigo in those days included several so-called nephritogenic strains that could lead to a dreaded complication: acute poststreptococcal glomerulonephritis (APSGN). Also called Bright disease, it could and did lead to fatal renal failure—about which little could be done at the time.
Fortunately, such nephritogenic strains of strep are unusual now, with APSGN occurring at a rate of about 1:1,000,000 in developed countries. In those locations, most people live far different lives today, bathing and changing clothes daily and living in much less cramped quarters.
The patient’s atopy likely had an impact, for several reasons: Since staph colonization of atopic persons is quite common, it’s more likely that an infection will develop. Also, thinner skin that is easily broken, a plethora of complicating problems (eg, dry skin, eczema, contact dermatitis, and exaggerated reactions to insect bites), and a lower threshold for itching all make atopic persons more susceptible to infection.
Most likely, our patient had a touch of eczema or dry skin and scratched it. Then, as the condition progressed, she scratched it more. The peroxide she used would have been highly irritating, serving only to worsen matters.
From a diagnostic point of view, the honey-colored crust covering the lesion and the context in which it developed led to a provisional diagnosis of impetiginized dermatitis. She was treated with oral cephalexin (500 mg tid for 7 d), topical mupirocin (applied bid), and topical hydrocortisone cream 2.5% (daily application). At one week’s follow-up, the patient’s skin was almost totally clear. It’s very unlikely she’ll have any residual scarring or blemish.
Had the diagnosis been unclear, or had the patient not responded to treatment, other diagnoses would have been considered. Among them: discoid lupus, psoriasis, contact dermatitis, and Darier disease.
ANSWER
The correct answer is impetigo (choice “c”), a superficial infection usually caused by a combination of staph and strep organisms.
Psoriasis (choice “a”) would have presented with white, tenacious scaling and would not have been acute in onset.
Eczema (choice “b”) is definitely possible, but the patient’s rash has features not seen with this condition; see Discussion for details.
Fungal infection (choice “d”) is also definitely in the differential, but it is unlikely given the negative KOH, the lack of any source for such infection, and the complete lack of response to tolnaftate cream.
DISCUSSION
Impetigo has also been called impetiginized dermatitis because it almost always starts with minor breaks in the skin as a result of conditions such as eczema, acne, contact dermatitis, or insect bite. Thus provided with access to deeper portions of the epithelial surface, bacterial organisms that normally cause no problems on intact skin are able to create a minor but annoying condition we have come to call impetigo.
Mistakenly called infantigo in large parts of the United States, impetigo is quite common but nonetheless alarming. Rarely associated with morbidity, it tends to resolve in two to three weeks at most, even without treatment.
Impetigo has the reputation of being highly contagious; given enough heat and humidity, close living conditions, and lack of regular bathing and/or adequate treatment, it can spread rapidly. Those conditions existed commonly 100 years ago, when bathing was sporadic and often cursory, and multiple family members lived and slept in close quarters. In those days before the introduction of antibiotics, there were no good topical antimicrobial agents, either.
Another factor played a major role in impetigo, bolstering its fearsome reputation. The strains of strep (group A b-hemolytic strep) that caused most impetigo in those days included several so-called nephritogenic strains that could lead to a dreaded complication: acute poststreptococcal glomerulonephritis (APSGN). Also called Bright disease, it could and did lead to fatal renal failure—about which little could be done at the time.
Fortunately, such nephritogenic strains of strep are unusual now, with APSGN occurring at a rate of about 1:1,000,000 in developed countries. In those locations, most people live far different lives today, bathing and changing clothes daily and living in much less cramped quarters.
The patient’s atopy likely had an impact, for several reasons: Since staph colonization of atopic persons is quite common, it’s more likely that an infection will develop. Also, thinner skin that is easily broken, a plethora of complicating problems (eg, dry skin, eczema, contact dermatitis, and exaggerated reactions to insect bites), and a lower threshold for itching all make atopic persons more susceptible to infection.
Most likely, our patient had a touch of eczema or dry skin and scratched it. Then, as the condition progressed, she scratched it more. The peroxide she used would have been highly irritating, serving only to worsen matters.
From a diagnostic point of view, the honey-colored crust covering the lesion and the context in which it developed led to a provisional diagnosis of impetiginized dermatitis. She was treated with oral cephalexin (500 mg tid for 7 d), topical mupirocin (applied bid), and topical hydrocortisone cream 2.5% (daily application). At one week’s follow-up, the patient’s skin was almost totally clear. It’s very unlikely she’ll have any residual scarring or blemish.
Had the diagnosis been unclear, or had the patient not responded to treatment, other diagnoses would have been considered. Among them: discoid lupus, psoriasis, contact dermatitis, and Darier disease.
A 16-year-old girl is referred to dermatology by her pediatrician for evaluation of a rash on her face. She is currently taking acyclovir (dose unknown) as prescribed by her pediatrician for presumed herpetic infection. Previous treatment attempts with OTC tolnaftate cream and various OTC moisturizers have failed. The rash manifested several weeks ago with two scaly bumps on her left cheek and temple area, which the patient admits to “picking” at. Initially, the lesions itched a bit, but they became larger and more symptomatic after she applied hydrogen peroxide to them several times. She then began to scrub the lesions vigorously with antibacterial soap while continuing to apply the peroxide. Subsequently, she presented to an urgent care clinic, where she was diagnosed with “ringworm” (and advised to use tolnaftate cream), and then to her pediatrician, with the aforementioned result. Aside from seasonal allergies and periodic episodes of eczema, the patient’s health is excellent. She has no pets. Examination reveals large, annular, honey-colored crusts focally located on the left side of the patient’s face. Faint pinkness is noted peripherally around the lesions. Modest but palpable adenopathy is detected in the pretragal and submental nodal areas. Though symptomatic, the patient is in no distress. A KOH prep taken from the scaly periphery is negative for fungal elements.
