Cutis

The Diagnosis: Pseudomonas Pyoderma

A skin swab confirmed the presence of a ciprofloxacinsusceptible Pseudomonas aeruginosa strain. Our patient received oral ciprofloxacin 500 mg twice daily for 10 days with remarkable clinical improvement. The remaining skin lesion was successfully treated with more frequent diaper changes and the use of topical corticosteroids and emollients.

The topographical location, cutaneous morphology, clinical context, and sometimes the type of exudate are fundamental for the diagnosis of eruptions in intertriginous areas. Cutaneous Candida infections are common in these locations. They classically present as markedly erythematous plaques that occasionally are erosive, accompanied by satellite papules and pustules.¹ Tinea cruris is a dermatophyte infection of the groin, proximal medial thighs, perineum, and buttocks. It usually presents as an erythematous patch that spreads centrifugally with partial central clearing and a slightly elevated, scaly border. Although candidiasis was higher on the differential, it was less likely, as our patient had a concomitant exudate inconsistent with Candida infections. Also, the lack of response to antifungal agents made hypotheses of fungal infections improbable.¹

Inverse psoriasis is a variant of psoriasis identified by the development of well-demarcated, nonscaly, shiny plaques on body folds.² Psoriasis is a chronic disease with several other cutaneous manifestations, such as nail and scalp involvement, as well as erythematous scaly plaques on the extensor surfaces of the limbs. The absence of a history of psoriasis, lack of other cutaneous manifestations, and no response to topical corticosteroids made the diagnosis of inverse psoriasis unlikely in our patient.

Erythrasma is a common superficial cutaneous infection caused by Corynebacterium minutissimum, a grampositive bacillus. It typically presents as an intertriginous eruption characterized by small erythematous to brown patches or thin plaques with fine scaling and sharp borders.³ Erythrasma displays a coral red fluorescence on Wood lamp examination that can be useful in the distinction from other causes of intertrigo.¹ Although this examination had not been performed in our patient, the striking exudate made erythrasma less likely, and the culture performed on skin swab material would help to rule out this diagnosis.

Pseudomonas aeruginosa is a gram-negative strict aerobic bacillus of ubiquitous distribution with a preference for humid environments.^4,5 Pseudomonas aeruginosa infections were first reported in the 19th century by physicians who noticed a peculiar odorous condition that caused a blue-green discoloration on bandages. This coloration explains the species name aeruginosa which is derived from the Latin word for copper rust.⁴ It comes from several water-soluble pigments produced by this microorganism, the most prevalent of which are pyocyanin and pyoverdine. Pyocyanin has a greenish-blue color and is nonfluorescent, while pyoverdine is green-yellowish and fluoresces under Wood light.⁵ Other pigments, such as pyorubin and pyomelanin, can be produced by some Pseudomonas strains.⁴

Pseudomonas aeruginosa has become one of the main pathogens involved in hospital-acquired infections,⁶ especially in immunocompromised patients.^6,7 It is a frequent cause of respiratory infections in patients with cystic fibrosis, as it is present in the airways of up to 70% of these patients in adulthood.⁷ Also, due to a variety of adaptive mechanisms with the development of resistance to a range of antibiotics, P aeruginosa has become a worldwide public health problem and is involved in several life-threatening nosocomial infections.^7,8

Cutaneous P aeruginosa infections range from superficial to deep tissue involvement and can affect both immunocompromised and immunocompetent individuals.⁹ They are classified as primary when they originate directly from the skin or secondary when they occur in the context of bacteremia. Primary infections mostly are mild and often are seen in healthy individuals; they usually occur by inoculation and predominate in moist areas where skin breakdown is frequent. Secondary infections typically affect immunocompromised individuals and portend a poor prognosis.^5,9

Denominated as Pseudomonas pyoderma, the superficial skin infection by P aeruginosa is described as a condition where the epidermis has a moth-eaten appearance with macerated or eroded borders.¹⁰ A blue-greenish exudate and a grape juice odor often are present. This infection usually occurs as a complication of several skin conditions such as tinea pedis, eczema, burns, wounds, and ulcers.^5,10

We believe that our patient developed Pseudomonas pyoderma as a complication of diaper dermatitis. His extended hospital stay with the use of different antibiotic regimens for the treatment of several infectious complications may have contributed to the development of infection by P aeruginosa.¹¹ Despite its great clinical relevance, there are few studies in the literature on primary skin infections caused by P aeruginosa, and clinical descriptions with images are rare. Our patient had a nonspecific noneczematous dermatitis, and the projections on the periphery of the lesion resembled the moth-eaten appearance of the classic description of Pseudomonas pyoderma.^5,10 The presence of a greenish exudate should promptly raise suspicion for this entity. We believe that the presentation of this case can illustrate this finding and help physicians to recognize this infection.

The Diagnosis: Pseudomonas Pyoderma

A skin swab confirmed the presence of a ciprofloxacinsusceptible Pseudomonas aeruginosa strain. Our patient received oral ciprofloxacin 500 mg twice daily for 10 days with remarkable clinical improvement. The remaining skin lesion was successfully treated with more frequent diaper changes and the use of topical corticosteroids and emollients.

The topographical location, cutaneous morphology, clinical context, and sometimes the type of exudate are fundamental for the diagnosis of eruptions in intertriginous areas. Cutaneous Candida infections are common in these locations. They classically present as markedly erythematous plaques that occasionally are erosive, accompanied by satellite papules and pustules.¹ Tinea cruris is a dermatophyte infection of the groin, proximal medial thighs, perineum, and buttocks. It usually presents as an erythematous patch that spreads centrifugally with partial central clearing and a slightly elevated, scaly border. Although candidiasis was higher on the differential, it was less likely, as our patient had a concomitant exudate inconsistent with Candida infections. Also, the lack of response to antifungal agents made hypotheses of fungal infections improbable.¹

Inverse psoriasis is a variant of psoriasis identified by the development of well-demarcated, nonscaly, shiny plaques on body folds.² Psoriasis is a chronic disease with several other cutaneous manifestations, such as nail and scalp involvement, as well as erythematous scaly plaques on the extensor surfaces of the limbs. The absence of a history of psoriasis, lack of other cutaneous manifestations, and no response to topical corticosteroids made the diagnosis of inverse psoriasis unlikely in our patient.

Erythrasma is a common superficial cutaneous infection caused by Corynebacterium minutissimum, a grampositive bacillus. It typically presents as an intertriginous eruption characterized by small erythematous to brown patches or thin plaques with fine scaling and sharp borders.³ Erythrasma displays a coral red fluorescence on Wood lamp examination that can be useful in the distinction from other causes of intertrigo.¹ Although this examination had not been performed in our patient, the striking exudate made erythrasma less likely, and the culture performed on skin swab material would help to rule out this diagnosis.

Pseudomonas aeruginosa is a gram-negative strict aerobic bacillus of ubiquitous distribution with a preference for humid environments.^4,5 Pseudomonas aeruginosa infections were first reported in the 19th century by physicians who noticed a peculiar odorous condition that caused a blue-green discoloration on bandages. This coloration explains the species name aeruginosa which is derived from the Latin word for copper rust.⁴ It comes from several water-soluble pigments produced by this microorganism, the most prevalent of which are pyocyanin and pyoverdine. Pyocyanin has a greenish-blue color and is nonfluorescent, while pyoverdine is green-yellowish and fluoresces under Wood light.⁵ Other pigments, such as pyorubin and pyomelanin, can be produced by some Pseudomonas strains.⁴

Pseudomonas aeruginosa has become one of the main pathogens involved in hospital-acquired infections,⁶ especially in immunocompromised patients.^6,7 It is a frequent cause of respiratory infections in patients with cystic fibrosis, as it is present in the airways of up to 70% of these patients in adulthood.⁷ Also, due to a variety of adaptive mechanisms with the development of resistance to a range of antibiotics, P aeruginosa has become a worldwide public health problem and is involved in several life-threatening nosocomial infections.^7,8

Cutaneous P aeruginosa infections range from superficial to deep tissue involvement and can affect both immunocompromised and immunocompetent individuals.⁹ They are classified as primary when they originate directly from the skin or secondary when they occur in the context of bacteremia. Primary infections mostly are mild and often are seen in healthy individuals; they usually occur by inoculation and predominate in moist areas where skin breakdown is frequent. Secondary infections typically affect immunocompromised individuals and portend a poor prognosis.^5,9

Denominated as Pseudomonas pyoderma, the superficial skin infection by P aeruginosa is described as a condition where the epidermis has a moth-eaten appearance with macerated or eroded borders.¹⁰ A blue-greenish exudate and a grape juice odor often are present. This infection usually occurs as a complication of several skin conditions such as tinea pedis, eczema, burns, wounds, and ulcers.^5,10

We believe that our patient developed Pseudomonas pyoderma as a complication of diaper dermatitis. His extended hospital stay with the use of different antibiotic regimens for the treatment of several infectious complications may have contributed to the development of infection by P aeruginosa.¹¹ Despite its great clinical relevance, there are few studies in the literature on primary skin infections caused by P aeruginosa, and clinical descriptions with images are rare. Our patient had a nonspecific noneczematous dermatitis, and the projections on the periphery of the lesion resembled the moth-eaten appearance of the classic description of Pseudomonas pyoderma.^5,10 The presence of a greenish exudate should promptly raise suspicion for this entity. We believe that the presentation of this case can illustrate this finding and help physicians to recognize this infection.

The Diagnosis: Pseudomonas Pyoderma

A skin swab confirmed the presence of a ciprofloxacinsusceptible Pseudomonas aeruginosa strain. Our patient received oral ciprofloxacin 500 mg twice daily for 10 days with remarkable clinical improvement. The remaining skin lesion was successfully treated with more frequent diaper changes and the use of topical corticosteroids and emollients.

The topographical location, cutaneous morphology, clinical context, and sometimes the type of exudate are fundamental for the diagnosis of eruptions in intertriginous areas. Cutaneous Candida infections are common in these locations. They classically present as markedly erythematous plaques that occasionally are erosive, accompanied by satellite papules and pustules.¹ Tinea cruris is a dermatophyte infection of the groin, proximal medial thighs, perineum, and buttocks. It usually presents as an erythematous patch that spreads centrifugally with partial central clearing and a slightly elevated, scaly border. Although candidiasis was higher on the differential, it was less likely, as our patient had a concomitant exudate inconsistent with Candida infections. Also, the lack of response to antifungal agents made hypotheses of fungal infections improbable.¹

Inverse psoriasis is a variant of psoriasis identified by the development of well-demarcated, nonscaly, shiny plaques on body folds.² Psoriasis is a chronic disease with several other cutaneous manifestations, such as nail and scalp involvement, as well as erythematous scaly plaques on the extensor surfaces of the limbs. The absence of a history of psoriasis, lack of other cutaneous manifestations, and no response to topical corticosteroids made the diagnosis of inverse psoriasis unlikely in our patient.

Erythrasma is a common superficial cutaneous infection caused by Corynebacterium minutissimum, a grampositive bacillus. It typically presents as an intertriginous eruption characterized by small erythematous to brown patches or thin plaques with fine scaling and sharp borders.³ Erythrasma displays a coral red fluorescence on Wood lamp examination that can be useful in the distinction from other causes of intertrigo.¹ Although this examination had not been performed in our patient, the striking exudate made erythrasma less likely, and the culture performed on skin swab material would help to rule out this diagnosis.

Pseudomonas aeruginosa is a gram-negative strict aerobic bacillus of ubiquitous distribution with a preference for humid environments.^4,5 Pseudomonas aeruginosa infections were first reported in the 19th century by physicians who noticed a peculiar odorous condition that caused a blue-green discoloration on bandages. This coloration explains the species name aeruginosa which is derived from the Latin word for copper rust.⁴ It comes from several water-soluble pigments produced by this microorganism, the most prevalent of which are pyocyanin and pyoverdine. Pyocyanin has a greenish-blue color and is nonfluorescent, while pyoverdine is green-yellowish and fluoresces under Wood light.⁵ Other pigments, such as pyorubin and pyomelanin, can be produced by some Pseudomonas strains.⁴

Pseudomonas aeruginosa has become one of the main pathogens involved in hospital-acquired infections,⁶ especially in immunocompromised patients.^6,7 It is a frequent cause of respiratory infections in patients with cystic fibrosis, as it is present in the airways of up to 70% of these patients in adulthood.⁷ Also, due to a variety of adaptive mechanisms with the development of resistance to a range of antibiotics, P aeruginosa has become a worldwide public health problem and is involved in several life-threatening nosocomial infections.^7,8

Cutaneous P aeruginosa infections range from superficial to deep tissue involvement and can affect both immunocompromised and immunocompetent individuals.⁹ They are classified as primary when they originate directly from the skin or secondary when they occur in the context of bacteremia. Primary infections mostly are mild and often are seen in healthy individuals; they usually occur by inoculation and predominate in moist areas where skin breakdown is frequent. Secondary infections typically affect immunocompromised individuals and portend a poor prognosis.^5,9

Denominated as Pseudomonas pyoderma, the superficial skin infection by P aeruginosa is described as a condition where the epidermis has a moth-eaten appearance with macerated or eroded borders.¹⁰ A blue-greenish exudate and a grape juice odor often are present. This infection usually occurs as a complication of several skin conditions such as tinea pedis, eczema, burns, wounds, and ulcers.^5,10

We believe that our patient developed Pseudomonas pyoderma as a complication of diaper dermatitis. His extended hospital stay with the use of different antibiotic regimens for the treatment of several infectious complications may have contributed to the development of infection by P aeruginosa.¹¹ Despite its great clinical relevance, there are few studies in the literature on primary skin infections caused by P aeruginosa, and clinical descriptions with images are rare. Our patient had a nonspecific noneczematous dermatitis, and the projections on the periphery of the lesion resembled the moth-eaten appearance of the classic description of Pseudomonas pyoderma.^5,10 The presence of a greenish exudate should promptly raise suspicion for this entity. We believe that the presentation of this case can illustrate this finding and help physicians to recognize this infection.

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

To the Editor:

A 53-year-old Hispanic woman presented to our dermatology clinic for evaluation of an expanding plaque on the right cheek of 2 months’ duration. The patient stated the plaque began as a pimple, which she picked with subsequent spread laterally across the cheek. The area was intermittently tender, but she denied tingling, burning, or pruritus of the site. She had been treated with doxycycline and amoxicillin–clavulanic acid prior to presentation without improvement. She had a history of levamisole-induced vasculitis approximately 6 months prior. A review of systems was notable for diffuse joint pain. The patient denied tobacco, alcohol, or illicit drug use in the preceding 3 months and denied any changes in her medications or in health within the last year.

Physical examination revealed a well-appearing, alert, and afebrile patient with a pink, well-demarcated plaque on the right cheek (Figure 1). The borders of the plaque were indurated, and the lateral aspect of the plaque was eroded secondary to digital manipulation by the patient. She had no cervical lymphadenopathy. There were no other abnormal cutaneous findings.

There is a broad differential diagnosis for a pink expanding plaque on the face, which requires histopathologic correlation for correct diagnosis. Three broad categories in the differential are infectious (eg, bacterial, fungal), medication related (eg, fixed drug eruption), and granulomatous (eg, granuloma faciale [GF], sarcoidosis, tumid lupus, leprosy, granulomatous rosacea). A biopsy of the lesion revealed a mixed inflammatory cell dermal infiltrate with perivascular accentuation and intense vasculitis that was consistent with GF (Figure 2). Gomori methenamine-silver, periodic acid–Schiff, Fite-Faraco, acid-fast bacilli, and Gram staining were negative for organisms. Tissue cultures were negative for bacterial, mycobacterial, and fungal etiology. The patient was started on high-potency topical steroids with a 50% improvement in the appearance of the skin lesion at 1-month follow-up.

Granuloma faciale is a rare chronic inflammatory dermatosis with a predilection for the face that is difficult to diagnose and treat. The diagnosis is based on clinical and histologic findings, and it typically presents as single or multiple, well-demarcated, red-brown nodules, papules, or plaques that range from several millimeters to centimeters in diameter.^1,2 Extrafacial lesions may be seen.³ Granuloma faciale usually is asymptomatic but occasionally has associated pruritus and rarely ulceration. The prevalence and pathophysiology of GF is not well defined; however, GF more commonly is reported in middle-aged White males.¹

Histologic examination of GF reveals a mixed inflammatory cellular infiltrate in the upper dermis. A grenz zone, which is a narrow area of the papillary dermis uninvolved by the underlying pathology, may be seen.¹ Contrary to the name, granulomas are not found histologically. Rather, vascular changes or damage frequently are present and may indicate a small vessel vasculitis pathologic mechanism. Granuloma faciale also has been associated with follicular ostia accentuation and telangiectases.⁴

Many cases of GF have been misdiagnosed as sarcoidosis, lymphoma, lupus, and basal cell carcinoma.¹ In addition, GF shares many clinical and histologic features with erythema elevatum diutinum (EED). However, the defining features that suggest EED over GF is that EED has a predilection for the skin overlying the joints. Histopathologically, EED displays granulomas and fibrosis with few eosinophils.^5,6

The variable response of GF to treatments and lack of efficacy data have contributed to the complexity and uncertainty of managing GF. The current first-line therapies are topical tacrolimus,⁷ cryotherapy,⁸ or corticosteroid therapy.⁹

To the Editor:

A 53-year-old Hispanic woman presented to our dermatology clinic for evaluation of an expanding plaque on the right cheek of 2 months’ duration. The patient stated the plaque began as a pimple, which she picked with subsequent spread laterally across the cheek. The area was intermittently tender, but she denied tingling, burning, or pruritus of the site. She had been treated with doxycycline and amoxicillin–clavulanic acid prior to presentation without improvement. She had a history of levamisole-induced vasculitis approximately 6 months prior. A review of systems was notable for diffuse joint pain. The patient denied tobacco, alcohol, or illicit drug use in the preceding 3 months and denied any changes in her medications or in health within the last year.

Physical examination revealed a well-appearing, alert, and afebrile patient with a pink, well-demarcated plaque on the right cheek (Figure 1). The borders of the plaque were indurated, and the lateral aspect of the plaque was eroded secondary to digital manipulation by the patient. She had no cervical lymphadenopathy. There were no other abnormal cutaneous findings.

There is a broad differential diagnosis for a pink expanding plaque on the face, which requires histopathologic correlation for correct diagnosis. Three broad categories in the differential are infectious (eg, bacterial, fungal), medication related (eg, fixed drug eruption), and granulomatous (eg, granuloma faciale [GF], sarcoidosis, tumid lupus, leprosy, granulomatous rosacea). A biopsy of the lesion revealed a mixed inflammatory cell dermal infiltrate with perivascular accentuation and intense vasculitis that was consistent with GF (Figure 2). Gomori methenamine-silver, periodic acid–Schiff, Fite-Faraco, acid-fast bacilli, and Gram staining were negative for organisms. Tissue cultures were negative for bacterial, mycobacterial, and fungal etiology. The patient was started on high-potency topical steroids with a 50% improvement in the appearance of the skin lesion at 1-month follow-up.

Granuloma faciale is a rare chronic inflammatory dermatosis with a predilection for the face that is difficult to diagnose and treat. The diagnosis is based on clinical and histologic findings, and it typically presents as single or multiple, well-demarcated, red-brown nodules, papules, or plaques that range from several millimeters to centimeters in diameter.^1,2 Extrafacial lesions may be seen.³ Granuloma faciale usually is asymptomatic but occasionally has associated pruritus and rarely ulceration. The prevalence and pathophysiology of GF is not well defined; however, GF more commonly is reported in middle-aged White males.¹

Histologic examination of GF reveals a mixed inflammatory cellular infiltrate in the upper dermis. A grenz zone, which is a narrow area of the papillary dermis uninvolved by the underlying pathology, may be seen.¹ Contrary to the name, granulomas are not found histologically. Rather, vascular changes or damage frequently are present and may indicate a small vessel vasculitis pathologic mechanism. Granuloma faciale also has been associated with follicular ostia accentuation and telangiectases.⁴

Many cases of GF have been misdiagnosed as sarcoidosis, lymphoma, lupus, and basal cell carcinoma.¹ In addition, GF shares many clinical and histologic features with erythema elevatum diutinum (EED). However, the defining features that suggest EED over GF is that EED has a predilection for the skin overlying the joints. Histopathologically, EED displays granulomas and fibrosis with few eosinophils.^5,6

The variable response of GF to treatments and lack of efficacy data have contributed to the complexity and uncertainty of managing GF. The current first-line therapies are topical tacrolimus,⁷ cryotherapy,⁸ or corticosteroid therapy.⁹

To the Editor:

A 53-year-old Hispanic woman presented to our dermatology clinic for evaluation of an expanding plaque on the right cheek of 2 months’ duration. The patient stated the plaque began as a pimple, which she picked with subsequent spread laterally across the cheek. The area was intermittently tender, but she denied tingling, burning, or pruritus of the site. She had been treated with doxycycline and amoxicillin–clavulanic acid prior to presentation without improvement. She had a history of levamisole-induced vasculitis approximately 6 months prior. A review of systems was notable for diffuse joint pain. The patient denied tobacco, alcohol, or illicit drug use in the preceding 3 months and denied any changes in her medications or in health within the last year.

Physical examination revealed a well-appearing, alert, and afebrile patient with a pink, well-demarcated plaque on the right cheek (Figure 1). The borders of the plaque were indurated, and the lateral aspect of the plaque was eroded secondary to digital manipulation by the patient. She had no cervical lymphadenopathy. There were no other abnormal cutaneous findings.

There is a broad differential diagnosis for a pink expanding plaque on the face, which requires histopathologic correlation for correct diagnosis. Three broad categories in the differential are infectious (eg, bacterial, fungal), medication related (eg, fixed drug eruption), and granulomatous (eg, granuloma faciale [GF], sarcoidosis, tumid lupus, leprosy, granulomatous rosacea). A biopsy of the lesion revealed a mixed inflammatory cell dermal infiltrate with perivascular accentuation and intense vasculitis that was consistent with GF (Figure 2). Gomori methenamine-silver, periodic acid–Schiff, Fite-Faraco, acid-fast bacilli, and Gram staining were negative for organisms. Tissue cultures were negative for bacterial, mycobacterial, and fungal etiology. The patient was started on high-potency topical steroids with a 50% improvement in the appearance of the skin lesion at 1-month follow-up.

Granuloma faciale is a rare chronic inflammatory dermatosis with a predilection for the face that is difficult to diagnose and treat. The diagnosis is based on clinical and histologic findings, and it typically presents as single or multiple, well-demarcated, red-brown nodules, papules, or plaques that range from several millimeters to centimeters in diameter.^1,2 Extrafacial lesions may be seen.³ Granuloma faciale usually is asymptomatic but occasionally has associated pruritus and rarely ulceration. The prevalence and pathophysiology of GF is not well defined; however, GF more commonly is reported in middle-aged White males.¹

Histologic examination of GF reveals a mixed inflammatory cellular infiltrate in the upper dermis. A grenz zone, which is a narrow area of the papillary dermis uninvolved by the underlying pathology, may be seen.¹ Contrary to the name, granulomas are not found histologically. Rather, vascular changes or damage frequently are present and may indicate a small vessel vasculitis pathologic mechanism. Granuloma faciale also has been associated with follicular ostia accentuation and telangiectases.⁴

Many cases of GF have been misdiagnosed as sarcoidosis, lymphoma, lupus, and basal cell carcinoma.¹ In addition, GF shares many clinical and histologic features with erythema elevatum diutinum (EED). However, the defining features that suggest EED over GF is that EED has a predilection for the skin overlying the joints. Histopathologically, EED displays granulomas and fibrosis with few eosinophils.^5,6

The variable response of GF to treatments and lack of efficacy data have contributed to the complexity and uncertainty of managing GF. The current first-line therapies are topical tacrolimus,⁷ cryotherapy,⁸ or corticosteroid therapy.⁹

Mohs micrographic surgery (MMS) frequently is used in surgical removal of cancerous cutaneous lesions on cosmetically sensitive areas and anatomically challenging sites, including the ears. The vascular supply of the ear is complex and includes several watershed regions that are susceptible to injury during surgical resection or operative closure.

Case Reports

Patient 1—An 82-year-old woman with a 100-pack-year smoking history and no known history of diabetes mellitus or coronary artery disease presented with a superficial and micronodular basal cell carcinoma (BCC) of the left postauricular skin of approximately 18 months’ duration. Mohs micrographic surgery was performed for lesion removal. The BCC was noted to be deeply penetrating and by the second stage was to the depth of the deep subcutaneous tissue (Figure 1A [inset]). Frozen section histopathology revealed a micronodular and superficial BCC. A 2.1×2.0-cm postoperative defect including the posterior surface of the ear, postauricular sulcus, and postauricular scalp remained. To minimize the area left to heal via secondary intention, partial layered closure was performed by placing four 4-0 polyglactin sutures from the scalp side of the defect on the postauricular skin to the postauricular sulcus (Figure 1A).

The patient presented to the clinic on postoperative day (POD) 4, noting pain and redness since the evening of the surgery on the anterior surface of the ear, specifically the cavum concha. Physical examination revealed that the incision site appeared to be healing as expected, but the cavum concha demonstrated erosions and ecchymosis (Figure 1B). A fluid culture was collected, and the patient was started on doxycycline 100 mg twice daily for 10 days. The patient returned to the clinic at POD 10 with skin sloughing and a small border of dark purple discoloration, consistent with early necrosis.

At the 1-month postsurgery follow-up visit, the wound had persistent anterior sloughing and discoloration with adherent debris suggestive of vascular compromise. At the 5-month wound check, the left conchal bowl had a 1-cm through-and-through defect of the concha cavum (Figure 1B [inset]). The favored etiology was occlusion of the posterior auricular artery during the patient’s MMS and reconstruction. Once healed, options including reconstruction, prosthesis, and no treatment were discussed with the patient. The patient decided to pursue partial closure of the defect.

Patient 2—A 71-year-old man with coronary artery disease and no known smoking or diabetes mellitus history presented with a 0.7×0.6-cm cutaneous squamous cell carcinoma of the left helix (Figure 2A [inset]). Mohs micrographic surgery was completed, resulting in a 1.1×1.0-cm defect that extended to the perichondrium. Given the location and size, a linear closure was performed with a deep layer of 5-0 polyglactin sutures and a cutaneous layer of 6-0 polypropylene sutures. The final closure length was 2.1 cm (Figure 2A).

On POD 14, the patient presented for suture removal and reported the onset of brown discoloration of the ear on POD 3. Physical examination revealed the left ear appeared dusky around the mid helix with extension onto the antihelix (Figure 2B). Because one of the main concerns was necrosis, a thin layer of nitropaste ointment 2% was prescribed to be applied twice daily to the affected area, in addition to liberal application of petroleum jelly. On POD 21, the left mid helix demonstrated a well-defined area of necrosis on the helical rim extending to the antihelix, and conservative treatment was continued. Four weeks later, the left ear had a prominent eschar, which was debrided. On follow-up 6 weeks later, the area was well healed with an obvious notched defect of the helix and scaphoid fossa (Figure 2B [inset]). The favored etiology was occlusion of the middle helical arcade during the patient’s MMS and reconstruction. Reconstructive options were discussed with the patient; however, he declined any further reconstructive intervention.

Comment

Auricular Vasculature—In our patients, the auricular vascular supply was compromised during routine MMS followed by reconstruction, resulting in tissue necrosis. Given the relative frequency of these procedures and the risk for tissue necrosis, a review of the auricular vasculature with special attention to the conchal bowl and helical rim was warranted (Figure 3).

The auricle is supplied by 2 main arterial sources arising from the external carotid artery: the superficial temporal artery (STA) supplying the anterior auricle and the posterior auricular artery (PAA) supplying the posterior auricle and the concha.¹ Anastomoses between these 2 blood supplies occur through perforating arteries and vascular arcades.

As the STA courses cranially, it moves from a deep position—deep to the parotidomasseteric fascia—to the superficial temporal fascia approximately 1 cm anterior and superior to the tragus. In approximately 80% of patients, 3 perpendicular branches stem from the STA—the upper, middle, and lower anterior branches—which supply the ascending helix, tragus, and lower margin of the earlobe, respectively.² The upper anterior branch of the STA joins other branches to form 2 dominant arcades: the first with the nonperforating branches of the PAA forming the upper third of the helical arcade, and the second with the lower anterior branch of the STA forming the middle portion of the helical arcade.^3,4 In 75% of patients, the middle helical arcade was identified as a single connecting artery, whereas in the remaining 25% of patients, a robust capillary network was formed.² In patient 2, the middle helical arcade was likely disrupted during closure, resulting in the helical necrosis seen postoperatively.

The second main blood supply of the auricle is the PAA, which enters in a more superficial position after traversing superiorly from the meatal cartilage, between the mastoid process and the posterior surface of the concha. From this point, the PAA runs in the deep subcutaneous tissue in the groove formed by the conchal cartilage and the mastoid process. Near the midpoint of the postauricular groove, it passes inferior to the postauricular muscle. The PAA has multiple radial branches that anastomose with helical branches; it also sends perforating branches (there were 2–4 branches in a recent study²) through the cartilage to the anterior surface of the concha. The 2 primary perforating arteries most commonly are located at the level of the antihelix and the antitragus.⁵ These arteries transverse through a vascular foramen located approximately 11 mm from the tragus in the horizontal plane and supply blood to the conchal bowl.⁶ In patient 1, the PAA itself, or the perforating arteries that course anteriorly through the vascular foramen, was likely disrupted, resulting in the conchal defect.

Special Considerations Before Surgery—As evidenced by these cases, special attention is needed during operative planning to account for the external ear vascular arcades. Damage to the helical arcades (patient 2) or the perforating arteries within the conchal bowl (patient 1) can lead to unintended consequences such as postoperative tissue necrosis. Tissue manipulation in these areas should be approached cautiously and with the least invasive treatment and closure options available. In doing so, blood flow and tissue integrity can be maintained, resulting in improved postoperative outcomes. Further research is warranted to identify the best intervention in cases involving these watershed regions.

Mohs micrographic surgery (MMS) frequently is used in surgical removal of cancerous cutaneous lesions on cosmetically sensitive areas and anatomically challenging sites, including the ears. The vascular supply of the ear is complex and includes several watershed regions that are susceptible to injury during surgical resection or operative closure.

Case Reports

Patient 1—An 82-year-old woman with a 100-pack-year smoking history and no known history of diabetes mellitus or coronary artery disease presented with a superficial and micronodular basal cell carcinoma (BCC) of the left postauricular skin of approximately 18 months’ duration. Mohs micrographic surgery was performed for lesion removal. The BCC was noted to be deeply penetrating and by the second stage was to the depth of the deep subcutaneous tissue (Figure 1A [inset]). Frozen section histopathology revealed a micronodular and superficial BCC. A 2.1×2.0-cm postoperative defect including the posterior surface of the ear, postauricular sulcus, and postauricular scalp remained. To minimize the area left to heal via secondary intention, partial layered closure was performed by placing four 4-0 polyglactin sutures from the scalp side of the defect on the postauricular skin to the postauricular sulcus (Figure 1A).

The patient presented to the clinic on postoperative day (POD) 4, noting pain and redness since the evening of the surgery on the anterior surface of the ear, specifically the cavum concha. Physical examination revealed that the incision site appeared to be healing as expected, but the cavum concha demonstrated erosions and ecchymosis (Figure 1B). A fluid culture was collected, and the patient was started on doxycycline 100 mg twice daily for 10 days. The patient returned to the clinic at POD 10 with skin sloughing and a small border of dark purple discoloration, consistent with early necrosis.

At the 1-month postsurgery follow-up visit, the wound had persistent anterior sloughing and discoloration with adherent debris suggestive of vascular compromise. At the 5-month wound check, the left conchal bowl had a 1-cm through-and-through defect of the concha cavum (Figure 1B [inset]). The favored etiology was occlusion of the posterior auricular artery during the patient’s MMS and reconstruction. Once healed, options including reconstruction, prosthesis, and no treatment were discussed with the patient. The patient decided to pursue partial closure of the defect.

Patient 2—A 71-year-old man with coronary artery disease and no known smoking or diabetes mellitus history presented with a 0.7×0.6-cm cutaneous squamous cell carcinoma of the left helix (Figure 2A [inset]). Mohs micrographic surgery was completed, resulting in a 1.1×1.0-cm defect that extended to the perichondrium. Given the location and size, a linear closure was performed with a deep layer of 5-0 polyglactin sutures and a cutaneous layer of 6-0 polypropylene sutures. The final closure length was 2.1 cm (Figure 2A).

On POD 14, the patient presented for suture removal and reported the onset of brown discoloration of the ear on POD 3. Physical examination revealed the left ear appeared dusky around the mid helix with extension onto the antihelix (Figure 2B). Because one of the main concerns was necrosis, a thin layer of nitropaste ointment 2% was prescribed to be applied twice daily to the affected area, in addition to liberal application of petroleum jelly. On POD 21, the left mid helix demonstrated a well-defined area of necrosis on the helical rim extending to the antihelix, and conservative treatment was continued. Four weeks later, the left ear had a prominent eschar, which was debrided. On follow-up 6 weeks later, the area was well healed with an obvious notched defect of the helix and scaphoid fossa (Figure 2B [inset]). The favored etiology was occlusion of the middle helical arcade during the patient’s MMS and reconstruction. Reconstructive options were discussed with the patient; however, he declined any further reconstructive intervention.

Comment

Auricular Vasculature—In our patients, the auricular vascular supply was compromised during routine MMS followed by reconstruction, resulting in tissue necrosis. Given the relative frequency of these procedures and the risk for tissue necrosis, a review of the auricular vasculature with special attention to the conchal bowl and helical rim was warranted (Figure 3).

The auricle is supplied by 2 main arterial sources arising from the external carotid artery: the superficial temporal artery (STA) supplying the anterior auricle and the posterior auricular artery (PAA) supplying the posterior auricle and the concha.¹ Anastomoses between these 2 blood supplies occur through perforating arteries and vascular arcades.

As the STA courses cranially, it moves from a deep position—deep to the parotidomasseteric fascia—to the superficial temporal fascia approximately 1 cm anterior and superior to the tragus. In approximately 80% of patients, 3 perpendicular branches stem from the STA—the upper, middle, and lower anterior branches—which supply the ascending helix, tragus, and lower margin of the earlobe, respectively.² The upper anterior branch of the STA joins other branches to form 2 dominant arcades: the first with the nonperforating branches of the PAA forming the upper third of the helical arcade, and the second with the lower anterior branch of the STA forming the middle portion of the helical arcade.^3,4 In 75% of patients, the middle helical arcade was identified as a single connecting artery, whereas in the remaining 25% of patients, a robust capillary network was formed.² In patient 2, the middle helical arcade was likely disrupted during closure, resulting in the helical necrosis seen postoperatively.

The second main blood supply of the auricle is the PAA, which enters in a more superficial position after traversing superiorly from the meatal cartilage, between the mastoid process and the posterior surface of the concha. From this point, the PAA runs in the deep subcutaneous tissue in the groove formed by the conchal cartilage and the mastoid process. Near the midpoint of the postauricular groove, it passes inferior to the postauricular muscle. The PAA has multiple radial branches that anastomose with helical branches; it also sends perforating branches (there were 2–4 branches in a recent study²) through the cartilage to the anterior surface of the concha. The 2 primary perforating arteries most commonly are located at the level of the antihelix and the antitragus.⁵ These arteries transverse through a vascular foramen located approximately 11 mm from the tragus in the horizontal plane and supply blood to the conchal bowl.⁶ In patient 1, the PAA itself, or the perforating arteries that course anteriorly through the vascular foramen, was likely disrupted, resulting in the conchal defect.

Special Considerations Before Surgery—As evidenced by these cases, special attention is needed during operative planning to account for the external ear vascular arcades. Damage to the helical arcades (patient 2) or the perforating arteries within the conchal bowl (patient 1) can lead to unintended consequences such as postoperative tissue necrosis. Tissue manipulation in these areas should be approached cautiously and with the least invasive treatment and closure options available. In doing so, blood flow and tissue integrity can be maintained, resulting in improved postoperative outcomes. Further research is warranted to identify the best intervention in cases involving these watershed regions.

Mohs micrographic surgery (MMS) frequently is used in surgical removal of cancerous cutaneous lesions on cosmetically sensitive areas and anatomically challenging sites, including the ears. The vascular supply of the ear is complex and includes several watershed regions that are susceptible to injury during surgical resection or operative closure.

Case Reports

Patient 1—An 82-year-old woman with a 100-pack-year smoking history and no known history of diabetes mellitus or coronary artery disease presented with a superficial and micronodular basal cell carcinoma (BCC) of the left postauricular skin of approximately 18 months’ duration. Mohs micrographic surgery was performed for lesion removal. The BCC was noted to be deeply penetrating and by the second stage was to the depth of the deep subcutaneous tissue (Figure 1A [inset]). Frozen section histopathology revealed a micronodular and superficial BCC. A 2.1×2.0-cm postoperative defect including the posterior surface of the ear, postauricular sulcus, and postauricular scalp remained. To minimize the area left to heal via secondary intention, partial layered closure was performed by placing four 4-0 polyglactin sutures from the scalp side of the defect on the postauricular skin to the postauricular sulcus (Figure 1A).

The patient presented to the clinic on postoperative day (POD) 4, noting pain and redness since the evening of the surgery on the anterior surface of the ear, specifically the cavum concha. Physical examination revealed that the incision site appeared to be healing as expected, but the cavum concha demonstrated erosions and ecchymosis (Figure 1B). A fluid culture was collected, and the patient was started on doxycycline 100 mg twice daily for 10 days. The patient returned to the clinic at POD 10 with skin sloughing and a small border of dark purple discoloration, consistent with early necrosis.

At the 1-month postsurgery follow-up visit, the wound had persistent anterior sloughing and discoloration with adherent debris suggestive of vascular compromise. At the 5-month wound check, the left conchal bowl had a 1-cm through-and-through defect of the concha cavum (Figure 1B [inset]). The favored etiology was occlusion of the posterior auricular artery during the patient’s MMS and reconstruction. Once healed, options including reconstruction, prosthesis, and no treatment were discussed with the patient. The patient decided to pursue partial closure of the defect.

Patient 2—A 71-year-old man with coronary artery disease and no known smoking or diabetes mellitus history presented with a 0.7×0.6-cm cutaneous squamous cell carcinoma of the left helix (Figure 2A [inset]). Mohs micrographic surgery was completed, resulting in a 1.1×1.0-cm defect that extended to the perichondrium. Given the location and size, a linear closure was performed with a deep layer of 5-0 polyglactin sutures and a cutaneous layer of 6-0 polypropylene sutures. The final closure length was 2.1 cm (Figure 2A).

On POD 14, the patient presented for suture removal and reported the onset of brown discoloration of the ear on POD 3. Physical examination revealed the left ear appeared dusky around the mid helix with extension onto the antihelix (Figure 2B). Because one of the main concerns was necrosis, a thin layer of nitropaste ointment 2% was prescribed to be applied twice daily to the affected area, in addition to liberal application of petroleum jelly. On POD 21, the left mid helix demonstrated a well-defined area of necrosis on the helical rim extending to the antihelix, and conservative treatment was continued. Four weeks later, the left ear had a prominent eschar, which was debrided. On follow-up 6 weeks later, the area was well healed with an obvious notched defect of the helix and scaphoid fossa (Figure 2B [inset]). The favored etiology was occlusion of the middle helical arcade during the patient’s MMS and reconstruction. Reconstructive options were discussed with the patient; however, he declined any further reconstructive intervention.

Comment

Auricular Vasculature—In our patients, the auricular vascular supply was compromised during routine MMS followed by reconstruction, resulting in tissue necrosis. Given the relative frequency of these procedures and the risk for tissue necrosis, a review of the auricular vasculature with special attention to the conchal bowl and helical rim was warranted (Figure 3).

The auricle is supplied by 2 main arterial sources arising from the external carotid artery: the superficial temporal artery (STA) supplying the anterior auricle and the posterior auricular artery (PAA) supplying the posterior auricle and the concha.¹ Anastomoses between these 2 blood supplies occur through perforating arteries and vascular arcades.

As the STA courses cranially, it moves from a deep position—deep to the parotidomasseteric fascia—to the superficial temporal fascia approximately 1 cm anterior and superior to the tragus. In approximately 80% of patients, 3 perpendicular branches stem from the STA—the upper, middle, and lower anterior branches—which supply the ascending helix, tragus, and lower margin of the earlobe, respectively.² The upper anterior branch of the STA joins other branches to form 2 dominant arcades: the first with the nonperforating branches of the PAA forming the upper third of the helical arcade, and the second with the lower anterior branch of the STA forming the middle portion of the helical arcade.^3,4 In 75% of patients, the middle helical arcade was identified as a single connecting artery, whereas in the remaining 25% of patients, a robust capillary network was formed.² In patient 2, the middle helical arcade was likely disrupted during closure, resulting in the helical necrosis seen postoperatively.

The second main blood supply of the auricle is the PAA, which enters in a more superficial position after traversing superiorly from the meatal cartilage, between the mastoid process and the posterior surface of the concha. From this point, the PAA runs in the deep subcutaneous tissue in the groove formed by the conchal cartilage and the mastoid process. Near the midpoint of the postauricular groove, it passes inferior to the postauricular muscle. The PAA has multiple radial branches that anastomose with helical branches; it also sends perforating branches (there were 2–4 branches in a recent study²) through the cartilage to the anterior surface of the concha. The 2 primary perforating arteries most commonly are located at the level of the antihelix and the antitragus.⁵ These arteries transverse through a vascular foramen located approximately 11 mm from the tragus in the horizontal plane and supply blood to the conchal bowl.⁶ In patient 1, the PAA itself, or the perforating arteries that course anteriorly through the vascular foramen, was likely disrupted, resulting in the conchal defect.

Special Considerations Before Surgery—As evidenced by these cases, special attention is needed during operative planning to account for the external ear vascular arcades. Damage to the helical arcades (patient 2) or the perforating arteries within the conchal bowl (patient 1) can lead to unintended consequences such as postoperative tissue necrosis. Tissue manipulation in these areas should be approached cautiously and with the least invasive treatment and closure options available. In doing so, blood flow and tissue integrity can be maintained, resulting in improved postoperative outcomes. Further research is warranted to identify the best intervention in cases involving these watershed regions.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶ KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶ KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶ KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

The Diagnosis: Cutaneous B-cell Lymphoma

Shave biopsies of 3 lesions revealed a dense, diffuse, atypical lymphoid infiltrate occupying the entirety of the dermis and obscuring the dermoepidermal junction. The infiltrate consisted predominantly of largesized lymphoid cells with fine chromatin and conspicuous nucleoli (Figure). Immunohistochemistry was positive for CD45 and CD20, indicating B-cell lineage. Bcl-2, multiple myeloma oncogene 1, and forkhead box protein P1 also were expressed in the vast majority of lesional cells, distinguishing the lesion from other forms of cutaneous B-cell lymphomas.¹ These findings were consistent with large B-cell lymphoma with a high proliferation index, consistent with primary cutaneous diffuse large B-cell lymphoma, leg type, which often presents on the lower leg.² The patient had a negative systemic workup including bone marrow biopsy. He was started on the R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone) chemotherapy regimen.

Primary cutaneous diffuse large B-cell lymphoma, leg type, is an intermediately aggressive and rare form of B-cell lymphoma with a poor prognosis that primarily affects elderly female patients. Primary cutaneous diffuse large B-cell lymphoma, leg type, accounts for only 1% to 3% of cutaneous lymphomas and approximately 10% to 20% of primary cutaneous B-cell lymphomas.² It typically presents as multiple red-brown or bluish nodules on the lower extremities or trunk. Presentation as a solitary nodule also is possible.^1,2 Histologic analysis of primary cutaneous diffuse large B-cell lymphoma, leg type, reveals large cells with round nuclei (immunoblasts and centroblasts), and the immunohistochemical profile shows strong Bcl-2 expression often accompanied by the multiple myeloma oncogene 1 protein.³ The 5-year survival rate is approximately 50%, which is lower than other types of primary cutaneous B-cell lymphomas, and the progression of disease is characterized by frequent relapses and involvement of extracutaneous regions such as the lymph nodes, bone marrow, and central nervous system.^1,2,4 Patients with multiple tumors on the leg have a particularly poor prognosis; in particular, having 1 or more lesions on the leg results in a 43% 3-year survival rate while having multiple lesions has a 36% 3-year survival rate compared with a 77% 3-year survival rate for patients with the non–leg subtype or a single lesion.3 Treatment with rituximab has been shown to be effective in at least short-term control of the disease, and the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is the standard of treatment.^3,4

Primary cutaneous diffuse large B-cell lymphoma, leg type, can mimic multiple other cutaneous presentations of disease. Myeloid sarcoma (leukemia cutis) is a rare condition that presents as an extramedullary tumor often simultaneously with the onset or relapse of acute myeloid leukemia.⁵ Our patient had no history of leukemia, but myeloid sarcoma may predate acute myeloid leukemia in about a quarter of cases.⁵ It most commonly presents histologically as a diffuse dermal infiltrate that splays between collagen bundles and often is associated with an overlying Grenz zone. A nodular, or perivascular and periadnexal, pattern also may be seen. Upon closer inspection, the infiltrate is composed of immature myeloid cells (blasts) with background inflammation occasionally containing eosinophils. The immunohistochemical profile varies depending on the type of differentiation and degree of maturity of the cells. The histologic findings in our patient were inconsistent with myeloid sarcoma.

Erythema elevatum diutinum (EED) usually presents as dark red, brown, or violaceous papules or plaques and often is found on the extensor surfaces. It often is associated with hematologic abnormalities as well as recurrent bacterial or viral infections.⁶ Histologically, EED initially manifests as leukocytoclastic vasculitis with a mixed inflammatory infiltrate typically featuring an abundance of neutrophils, making this condition unlikely in this case. As the lesion progresses, fibrosis and scarring ensue as inflammation wanes. The fibrosis often is described as having an onion skin–like pattern, which is characteristic of established EED lesions. Our patient had no history of vasculitis, and the histologic findings were inconsistent with EED.

Angiosarcoma can present as a central nodule surrounded by an erythematous plaque. Although potentially clinically similar to primary cutaneous diffuse large B-cell lymphoma, leg type, angiosarcoma was unlikely in this case because of an absence of lymphedema and no history of radiation to the leg, both of which are key historical features of angiosarcoma.⁷ Additionally, the histology of cutaneous angiosarcoma is marked by vascular proliferation, which was not seen in the lesion biopsied in our patient. The histology of angiosarcoma is that of an atypical vascular proliferation, and a hallmark feature is infiltration between collagen, often referred to as giving the appearance of dissection between collagen bundles. The degree of atypia can vary widely, and epithelioid variants exist, producing a potential diagnostic pitfall. Lesional cells are positive for vascular markers, which can be used for confirmation of the endothelial lineage.

Sarcoidosis is notorious for its mimicry, which can be the case both clinically and histologically. Characteristic pathology of sarcoidosis is that of well-formed epithelioid granulomas with minimal associated inflammation and lack of caseating necrosis. Our patient had no known history of systemic sarcoidosis, and the pathologic features of noncaseating granulomas were not present. As a diagnosis of exclusion, correlation with special stains and culture studies is necessary to exclude an infectious process. The differential diagnosis for sarcoidal granulomatous dermatitis also includes foreign body reaction, inflammatory bowel disease, and granulomatous cheilitis, among others.

The Diagnosis: Cutaneous B-cell Lymphoma

Shave biopsies of 3 lesions revealed a dense, diffuse, atypical lymphoid infiltrate occupying the entirety of the dermis and obscuring the dermoepidermal junction. The infiltrate consisted predominantly of largesized lymphoid cells with fine chromatin and conspicuous nucleoli (Figure). Immunohistochemistry was positive for CD45 and CD20, indicating B-cell lineage. Bcl-2, multiple myeloma oncogene 1, and forkhead box protein P1 also were expressed in the vast majority of lesional cells, distinguishing the lesion from other forms of cutaneous B-cell lymphomas.¹ These findings were consistent with large B-cell lymphoma with a high proliferation index, consistent with primary cutaneous diffuse large B-cell lymphoma, leg type, which often presents on the lower leg.² The patient had a negative systemic workup including bone marrow biopsy. He was started on the R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone) chemotherapy regimen.

Primary cutaneous diffuse large B-cell lymphoma, leg type, is an intermediately aggressive and rare form of B-cell lymphoma with a poor prognosis that primarily affects elderly female patients. Primary cutaneous diffuse large B-cell lymphoma, leg type, accounts for only 1% to 3% of cutaneous lymphomas and approximately 10% to 20% of primary cutaneous B-cell lymphomas.² It typically presents as multiple red-brown or bluish nodules on the lower extremities or trunk. Presentation as a solitary nodule also is possible.^1,2 Histologic analysis of primary cutaneous diffuse large B-cell lymphoma, leg type, reveals large cells with round nuclei (immunoblasts and centroblasts), and the immunohistochemical profile shows strong Bcl-2 expression often accompanied by the multiple myeloma oncogene 1 protein.³ The 5-year survival rate is approximately 50%, which is lower than other types of primary cutaneous B-cell lymphomas, and the progression of disease is characterized by frequent relapses and involvement of extracutaneous regions such as the lymph nodes, bone marrow, and central nervous system.^1,2,4 Patients with multiple tumors on the leg have a particularly poor prognosis; in particular, having 1 or more lesions on the leg results in a 43% 3-year survival rate while having multiple lesions has a 36% 3-year survival rate compared with a 77% 3-year survival rate for patients with the non–leg subtype or a single lesion.3 Treatment with rituximab has been shown to be effective in at least short-term control of the disease, and the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is the standard of treatment.^3,4

Primary cutaneous diffuse large B-cell lymphoma, leg type, can mimic multiple other cutaneous presentations of disease. Myeloid sarcoma (leukemia cutis) is a rare condition that presents as an extramedullary tumor often simultaneously with the onset or relapse of acute myeloid leukemia.⁵ Our patient had no history of leukemia, but myeloid sarcoma may predate acute myeloid leukemia in about a quarter of cases.⁵ It most commonly presents histologically as a diffuse dermal infiltrate that splays between collagen bundles and often is associated with an overlying Grenz zone. A nodular, or perivascular and periadnexal, pattern also may be seen. Upon closer inspection, the infiltrate is composed of immature myeloid cells (blasts) with background inflammation occasionally containing eosinophils. The immunohistochemical profile varies depending on the type of differentiation and degree of maturity of the cells. The histologic findings in our patient were inconsistent with myeloid sarcoma.

Erythema elevatum diutinum (EED) usually presents as dark red, brown, or violaceous papules or plaques and often is found on the extensor surfaces. It often is associated with hematologic abnormalities as well as recurrent bacterial or viral infections.⁶ Histologically, EED initially manifests as leukocytoclastic vasculitis with a mixed inflammatory infiltrate typically featuring an abundance of neutrophils, making this condition unlikely in this case. As the lesion progresses, fibrosis and scarring ensue as inflammation wanes. The fibrosis often is described as having an onion skin–like pattern, which is characteristic of established EED lesions. Our patient had no history of vasculitis, and the histologic findings were inconsistent with EED.

Angiosarcoma can present as a central nodule surrounded by an erythematous plaque. Although potentially clinically similar to primary cutaneous diffuse large B-cell lymphoma, leg type, angiosarcoma was unlikely in this case because of an absence of lymphedema and no history of radiation to the leg, both of which are key historical features of angiosarcoma.⁷ Additionally, the histology of cutaneous angiosarcoma is marked by vascular proliferation, which was not seen in the lesion biopsied in our patient. The histology of angiosarcoma is that of an atypical vascular proliferation, and a hallmark feature is infiltration between collagen, often referred to as giving the appearance of dissection between collagen bundles. The degree of atypia can vary widely, and epithelioid variants exist, producing a potential diagnostic pitfall. Lesional cells are positive for vascular markers, which can be used for confirmation of the endothelial lineage.

Sarcoidosis is notorious for its mimicry, which can be the case both clinically and histologically. Characteristic pathology of sarcoidosis is that of well-formed epithelioid granulomas with minimal associated inflammation and lack of caseating necrosis. Our patient had no known history of systemic sarcoidosis, and the pathologic features of noncaseating granulomas were not present. As a diagnosis of exclusion, correlation with special stains and culture studies is necessary to exclude an infectious process. The differential diagnosis for sarcoidal granulomatous dermatitis also includes foreign body reaction, inflammatory bowel disease, and granulomatous cheilitis, among others.

The Diagnosis: Cutaneous B-cell Lymphoma

Shave biopsies of 3 lesions revealed a dense, diffuse, atypical lymphoid infiltrate occupying the entirety of the dermis and obscuring the dermoepidermal junction. The infiltrate consisted predominantly of largesized lymphoid cells with fine chromatin and conspicuous nucleoli (Figure). Immunohistochemistry was positive for CD45 and CD20, indicating B-cell lineage. Bcl-2, multiple myeloma oncogene 1, and forkhead box protein P1 also were expressed in the vast majority of lesional cells, distinguishing the lesion from other forms of cutaneous B-cell lymphomas.¹ These findings were consistent with large B-cell lymphoma with a high proliferation index, consistent with primary cutaneous diffuse large B-cell lymphoma, leg type, which often presents on the lower leg.² The patient had a negative systemic workup including bone marrow biopsy. He was started on the R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone) chemotherapy regimen.

Primary cutaneous diffuse large B-cell lymphoma, leg type, is an intermediately aggressive and rare form of B-cell lymphoma with a poor prognosis that primarily affects elderly female patients. Primary cutaneous diffuse large B-cell lymphoma, leg type, accounts for only 1% to 3% of cutaneous lymphomas and approximately 10% to 20% of primary cutaneous B-cell lymphomas.² It typically presents as multiple red-brown or bluish nodules on the lower extremities or trunk. Presentation as a solitary nodule also is possible.^1,2 Histologic analysis of primary cutaneous diffuse large B-cell lymphoma, leg type, reveals large cells with round nuclei (immunoblasts and centroblasts), and the immunohistochemical profile shows strong Bcl-2 expression often accompanied by the multiple myeloma oncogene 1 protein.³ The 5-year survival rate is approximately 50%, which is lower than other types of primary cutaneous B-cell lymphomas, and the progression of disease is characterized by frequent relapses and involvement of extracutaneous regions such as the lymph nodes, bone marrow, and central nervous system.^1,2,4 Patients with multiple tumors on the leg have a particularly poor prognosis; in particular, having 1 or more lesions on the leg results in a 43% 3-year survival rate while having multiple lesions has a 36% 3-year survival rate compared with a 77% 3-year survival rate for patients with the non–leg subtype or a single lesion.3 Treatment with rituximab has been shown to be effective in at least short-term control of the disease, and the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is the standard of treatment.^3,4

Primary cutaneous diffuse large B-cell lymphoma, leg type, can mimic multiple other cutaneous presentations of disease. Myeloid sarcoma (leukemia cutis) is a rare condition that presents as an extramedullary tumor often simultaneously with the onset or relapse of acute myeloid leukemia.⁵ Our patient had no history of leukemia, but myeloid sarcoma may predate acute myeloid leukemia in about a quarter of cases.⁵ It most commonly presents histologically as a diffuse dermal infiltrate that splays between collagen bundles and often is associated with an overlying Grenz zone. A nodular, or perivascular and periadnexal, pattern also may be seen. Upon closer inspection, the infiltrate is composed of immature myeloid cells (blasts) with background inflammation occasionally containing eosinophils. The immunohistochemical profile varies depending on the type of differentiation and degree of maturity of the cells. The histologic findings in our patient were inconsistent with myeloid sarcoma.

Erythema elevatum diutinum (EED) usually presents as dark red, brown, or violaceous papules or plaques and often is found on the extensor surfaces. It often is associated with hematologic abnormalities as well as recurrent bacterial or viral infections.⁶ Histologically, EED initially manifests as leukocytoclastic vasculitis with a mixed inflammatory infiltrate typically featuring an abundance of neutrophils, making this condition unlikely in this case. As the lesion progresses, fibrosis and scarring ensue as inflammation wanes. The fibrosis often is described as having an onion skin–like pattern, which is characteristic of established EED lesions. Our patient had no history of vasculitis, and the histologic findings were inconsistent with EED.

Angiosarcoma can present as a central nodule surrounded by an erythematous plaque. Although potentially clinically similar to primary cutaneous diffuse large B-cell lymphoma, leg type, angiosarcoma was unlikely in this case because of an absence of lymphedema and no history of radiation to the leg, both of which are key historical features of angiosarcoma.⁷ Additionally, the histology of cutaneous angiosarcoma is marked by vascular proliferation, which was not seen in the lesion biopsied in our patient. The histology of angiosarcoma is that of an atypical vascular proliferation, and a hallmark feature is infiltration between collagen, often referred to as giving the appearance of dissection between collagen bundles. The degree of atypia can vary widely, and epithelioid variants exist, producing a potential diagnostic pitfall. Lesional cells are positive for vascular markers, which can be used for confirmation of the endothelial lineage.

Sarcoidosis is notorious for its mimicry, which can be the case both clinically and histologically. Characteristic pathology of sarcoidosis is that of well-formed epithelioid granulomas with minimal associated inflammation and lack of caseating necrosis. Our patient had no known history of systemic sarcoidosis, and the pathologic features of noncaseating granulomas were not present. As a diagnosis of exclusion, correlation with special stains and culture studies is necessary to exclude an infectious process. The differential diagnosis for sarcoidal granulomatous dermatitis also includes foreign body reaction, inflammatory bowel disease, and granulomatous cheilitis, among others.

Photographs courtesy of Richard P. Usatine, MD.

THE PRESENTATION

A Early central centrifugal cicatricial alopecia with a small central patch of hair loss in a 45-year-old Black woman.

B Late central centrifugal cicatricial alopecia with a large central patch of hair loss in a 43-year-old Black woman.

Scarring alopecia is a collection of hair loss disorders including chronic cutaneous lupus erythematosus (discoid lupus), lichen planopilaris, dissecting cellulitis, acne keloidalis, and central centrifugal cicatricial alopecia (CCCA).¹ Central centrifugal cicatricial alopecia (formerly hot comb alopecia or follicular degeneration syndrome) is a progressive, scarring, inflammatory alopecia and represents the most common form of scarring alopecia in women of African descent. It results in permanent destruction of hair follicles.

Epidemiology

Central centrifugal cicatricial alopecia predominantly affects women of African descent but also may affect men. The prevalence of CCCA in those of African descent has varied in the literature. Khumalo² reported a prevalence of 1.2% for women younger than 50 years and 6.7% in women older than 50 years. Central centrifugal cicatricial alopecia has been reported in other ethnic groups, such as those of Asian descent.³

Historically, hair care practices that are more common in those of African descent, such as high-tension hairstyles as well as heat and chemical hair relaxers, were implicated in the development of CCCA. However, the causes of CCCA are most likely multifactorial, including family history, genetic mutations, and hair care practices.^4-7 PADI3 mutations likely predispose some women to CCCA. Mutations in PADI3, which encodes peptidyl arginine deiminase 3 (an enzyme that modifies proteins crucial for the formation of hair shafts), were found in some patients with CCCA.⁸ Moreover, other genetic defects also likely play a role.⁷

Key clinical features

Early recognition is key for patients with CCCA.

• Central centrifugal cicatricial alopecia begins in the central scalp (crown area, vertex) and spreads centrifugally.

• Scalp symptoms such as tenderness, pain, a tingling or crawling sensation, and itching may occur.⁹ Some patients may not have any symptoms at all, and hair loss may progress painlessly.

• Central hair breakage—forme fruste CCCA—may be a presenting sign of CCCA.⁹

• Loss of follicular ostia and mottled hypopigmented and hyperpigmented macules are common findings.⁶

• Central centrifugal cicatricial alopecia can be diagnosed clinically and by histopathology.

Worth noting

Patients may experience hair loss and scalp symptoms for years before seeking medical evaluation. In some cultures, hair breakage or itching on the top of the scalp may be viewed as a normal occurrence in life.

It is important to set patient expectations that CCCA is a scarring alopecia, and the initial goal often is to maintain the patient's existing hair. However, hair and areas responding to treatment should still be treated. Without any intervention, the resulting scarring from CCCA may permanently scar follicles on the entire scalp.

Due to the inflammatory nature of CCCA, potent topical corticosteroids (eg, clobetasol propionate), intralesional corticosteroids (eg, triamcinolone acetonide), and oral anti-inflammatory agents (eg, doxycycline) are utilized in the treatment of CCCA. Minoxidil is another treatment option. Adjuvant therapies such as topical metformin also have been tried.¹⁰ Importantly, treatment of CCCA may halt further permanent destruction of hair follicles, but scalp symptoms may reappear periodically and require re-treatment with anti-inflammatory agents.

Health care highlight

Thorough scalp examination and awareness of clinical features of CCCA may prompt earlier diagnosis and prevent future severe permanent alopecia. Clinicians should encourage patients with suggestive signs or symptoms of CCCA to seek care from a dermatologist.

Photographs courtesy of Richard P. Usatine, MD.

THE PRESENTATION

A Early central centrifugal cicatricial alopecia with a small central patch of hair loss in a 45-year-old Black woman.

B Late central centrifugal cicatricial alopecia with a large central patch of hair loss in a 43-year-old Black woman.

Scarring alopecia is a collection of hair loss disorders including chronic cutaneous lupus erythematosus (discoid lupus), lichen planopilaris, dissecting cellulitis, acne keloidalis, and central centrifugal cicatricial alopecia (CCCA).¹ Central centrifugal cicatricial alopecia (formerly hot comb alopecia or follicular degeneration syndrome) is a progressive, scarring, inflammatory alopecia and represents the most common form of scarring alopecia in women of African descent. It results in permanent destruction of hair follicles.

Epidemiology

Central centrifugal cicatricial alopecia predominantly affects women of African descent but also may affect men. The prevalence of CCCA in those of African descent has varied in the literature. Khumalo² reported a prevalence of 1.2% for women younger than 50 years and 6.7% in women older than 50 years. Central centrifugal cicatricial alopecia has been reported in other ethnic groups, such as those of Asian descent.³

Historically, hair care practices that are more common in those of African descent, such as high-tension hairstyles as well as heat and chemical hair relaxers, were implicated in the development of CCCA. However, the causes of CCCA are most likely multifactorial, including family history, genetic mutations, and hair care practices.^4-7 PADI3 mutations likely predispose some women to CCCA. Mutations in PADI3, which encodes peptidyl arginine deiminase 3 (an enzyme that modifies proteins crucial for the formation of hair shafts), were found in some patients with CCCA.⁸ Moreover, other genetic defects also likely play a role.⁷

Key clinical features

Early recognition is key for patients with CCCA.

• Central centrifugal cicatricial alopecia begins in the central scalp (crown area, vertex) and spreads centrifugally.

• Scalp symptoms such as tenderness, pain, a tingling or crawling sensation, and itching may occur.⁹ Some patients may not have any symptoms at all, and hair loss may progress painlessly.

• Central hair breakage—forme fruste CCCA—may be a presenting sign of CCCA.⁹

• Loss of follicular ostia and mottled hypopigmented and hyperpigmented macules are common findings.⁶

• Central centrifugal cicatricial alopecia can be diagnosed clinically and by histopathology.

Worth noting

Patients may experience hair loss and scalp symptoms for years before seeking medical evaluation. In some cultures, hair breakage or itching on the top of the scalp may be viewed as a normal occurrence in life.

It is important to set patient expectations that CCCA is a scarring alopecia, and the initial goal often is to maintain the patient's existing hair. However, hair and areas responding to treatment should still be treated. Without any intervention, the resulting scarring from CCCA may permanently scar follicles on the entire scalp.

Due to the inflammatory nature of CCCA, potent topical corticosteroids (eg, clobetasol propionate), intralesional corticosteroids (eg, triamcinolone acetonide), and oral anti-inflammatory agents (eg, doxycycline) are utilized in the treatment of CCCA. Minoxidil is another treatment option. Adjuvant therapies such as topical metformin also have been tried.¹⁰ Importantly, treatment of CCCA may halt further permanent destruction of hair follicles, but scalp symptoms may reappear periodically and require re-treatment with anti-inflammatory agents.

Health care highlight

Thorough scalp examination and awareness of clinical features of CCCA may prompt earlier diagnosis and prevent future severe permanent alopecia. Clinicians should encourage patients with suggestive signs or symptoms of CCCA to seek care from a dermatologist.

Photographs courtesy of Richard P. Usatine, MD.

THE PRESENTATION

A Early central centrifugal cicatricial alopecia with a small central patch of hair loss in a 45-year-old Black woman.

B Late central centrifugal cicatricial alopecia with a large central patch of hair loss in a 43-year-old Black woman.

Scarring alopecia is a collection of hair loss disorders including chronic cutaneous lupus erythematosus (discoid lupus), lichen planopilaris, dissecting cellulitis, acne keloidalis, and central centrifugal cicatricial alopecia (CCCA).¹ Central centrifugal cicatricial alopecia (formerly hot comb alopecia or follicular degeneration syndrome) is a progressive, scarring, inflammatory alopecia and represents the most common form of scarring alopecia in women of African descent. It results in permanent destruction of hair follicles.

Epidemiology

Central centrifugal cicatricial alopecia predominantly affects women of African descent but also may affect men. The prevalence of CCCA in those of African descent has varied in the literature. Khumalo² reported a prevalence of 1.2% for women younger than 50 years and 6.7% in women older than 50 years. Central centrifugal cicatricial alopecia has been reported in other ethnic groups, such as those of Asian descent.³

Historically, hair care practices that are more common in those of African descent, such as high-tension hairstyles as well as heat and chemical hair relaxers, were implicated in the development of CCCA. However, the causes of CCCA are most likely multifactorial, including family history, genetic mutations, and hair care practices.^4-7 PADI3 mutations likely predispose some women to CCCA. Mutations in PADI3, which encodes peptidyl arginine deiminase 3 (an enzyme that modifies proteins crucial for the formation of hair shafts), were found in some patients with CCCA.⁸ Moreover, other genetic defects also likely play a role.⁷

Key clinical features

Early recognition is key for patients with CCCA.

• Central centrifugal cicatricial alopecia begins in the central scalp (crown area, vertex) and spreads centrifugally.

• Scalp symptoms such as tenderness, pain, a tingling or crawling sensation, and itching may occur.⁹ Some patients may not have any symptoms at all, and hair loss may progress painlessly.

• Central hair breakage—forme fruste CCCA—may be a presenting sign of CCCA.⁹

• Loss of follicular ostia and mottled hypopigmented and hyperpigmented macules are common findings.⁶

• Central centrifugal cicatricial alopecia can be diagnosed clinically and by histopathology.

Worth noting

Patients may experience hair loss and scalp symptoms for years before seeking medical evaluation. In some cultures, hair breakage or itching on the top of the scalp may be viewed as a normal occurrence in life.

It is important to set patient expectations that CCCA is a scarring alopecia, and the initial goal often is to maintain the patient's existing hair. However, hair and areas responding to treatment should still be treated. Without any intervention, the resulting scarring from CCCA may permanently scar follicles on the entire scalp.

Due to the inflammatory nature of CCCA, potent topical corticosteroids (eg, clobetasol propionate), intralesional corticosteroids (eg, triamcinolone acetonide), and oral anti-inflammatory agents (eg, doxycycline) are utilized in the treatment of CCCA. Minoxidil is another treatment option. Adjuvant therapies such as topical metformin also have been tried.¹⁰ Importantly, treatment of CCCA may halt further permanent destruction of hair follicles, but scalp symptoms may reappear periodically and require re-treatment with anti-inflammatory agents.

Health care highlight

Thorough scalp examination and awareness of clinical features of CCCA may prompt earlier diagnosis and prevent future severe permanent alopecia. Clinicians should encourage patients with suggestive signs or symptoms of CCCA to seek care from a dermatologist.

The Diagnosis: Perforating Rheumatoid Nodule

Perforating rheumatoid nodule (RN) is a variant of RN that demonstrates necrobiotic material extruding through the epidermis via the process of transepidermal elimination.¹ The necrobiotic material contains fibrin and often harbors karyorrhectic debris. The pathogenesis of RN remains unclear; possible mechanisms include a small vessel vasculitis or mechanical trauma inciting a localized aggregation of inflammatory products and rheumatoid factor complexes. This induces macrophage activation, fibrin deposition, and necrosis.² The majority of patients with RNs have detectable rheumatoid factor and anticyclic citrullinated protein in the blood.³ Rheumatoid nodules are the most common cutaneous manifestations of rheumatoid arthritis (RA) and will develop in 30% to 40% of RA patients.^4,5 They typically are associated with advanced RA but may precede the onset of clinically severe RA in 5% to 10% of patients.5 Rheumatoid nodules generally range in size from 2 mm to 5 cm and are slightly more prevalent in men than in women. They present as firm painless masses typically on the extensor surfaces of the hands and olecranon process but can occur over any tendinous or ligamentlike structure.^6,7 Perforating RNs are most common on areas subjected to pressure or repeated trauma, such as the sacrum.

The diagnosis usually is clinical; however, in cases of diagnostic uncertainty, RN can be distinguished by its histologic appearance. Rheumatoid nodules demonstrate granulomatous palisading necrobiosis with a central zone of highly eosinophilic fibrinoid necrobiosis surrounded by palisading mononuclear cells and an outer zone of granulation tissue. There may be a mixed chronic inflammatory infiltrate predominantly composed of lymphocytes and histiocytes in the background.

Rheumatoid nodules typically do not require treatment; however, perforation is known to increase the risk for infection, and surgical excision generally is indicated for prophylaxis against infection, though nodules may recur in the excision area.^1,3,8 Alternatively, disease-modifying antirheumatic drugs and intralesional corticosteroids may effectively reduce the size of RNs. The differential diagnosis for perforating RNs includes epithelioid sarcoma, perforating granuloma annulare, necrobiotic xanthogranuloma, and necrobiosis lipoidica.

Epithelioid sarcoma is a malignant soft tissue tumor typically found on the upper extremities of adolescent or young adult males. They usually present as hard tender nodules that commonly ulcerate. Epithelioid sarcoma makes up less than 1% of soft tissue sarcomas.⁹ Although rare, they present a diagnostic pitfall, as the histology may mimic an inflammatory palisaded granulomatous dermatitis similar to RN and granuloma annulare, thus a high index of suspicion is required to not overlook this aggressive malignancy. Histology is typified by nodular aggregates of epithelioid cells with abundant eosinophilic cytoplasm and often with central zones of necrosis (Figure 1). Epithelioid sarcoma displays immunoreactivity to cytokeratin, CD34, and epithelial membrane antigen, but loss of integrase interactor 1 expression. Cytologic abnormalities such as pleomorphism and hyperchromatism can be helpful in distinguishing between epithelioid sarcoma and RN.

Perforating granuloma annulare is a rare subtype of granuloma annulare that presents with flesh- to red-colored papules that develop central crust or scale. Perforating granuloma annulare composes approximately 5% of granuloma annulare cases. Perforating granuloma annulare can develop on any region of the body but has an affinity for the extensor surfaces of the extremities. It most frequently occurs in young women and rarely presents as a single lesion.¹⁰ Granuloma annulare typically is not associated with joint pain, and thus it differs from most cases of RNs. Histologically, it presents with an inflammatory palisading granuloma. There may be overlying epidermal thinning or parakeratosis, which can progress to perforation and extrusion of necrobiotic material. In comparison with RN, perforating granuloma annulare displays mucin deposition in the necrobiotic zones in lieu of fibrin (Figure 2).^10,11

Necrobiotic xanthogranuloma is a rare chronic form of non-Langerhans histiocytosis that characteristically presents with yellow or violaceous indurated plaques and nodules in a periorbital distribution. It often is associated with monoclonal gammopathy of IgG-κ. Lesions will ulcerate in 40% to 50% of patients.¹² The mean age at presentation is in the sixth decade of life, and it is moderately predominant in females.13 Histopathology demonstrates palisading granulomatous formations with a lymphoplasmacytic infiltrate and zones of necrobiosis in the mid dermis extending into the panniculus. Characteristic histologic features that are variably present in necrobiotic xanthogranuloma but typically absent in RN include neutrophilic debris, cholesterol clefts, and Touton or foreign body giant cells (Figure 3).¹³

Necrobiosis lipoidica is a rare chronic granulomatous disease characterized by well-demarcated, atrophic, yellow-brown plaques on the pretibial surfaces. It typically presents in the third decade of life in women, and most cases are associated with diabetes mellitus types 1 or 2 or autoimmune conditions.14 Necrobiosis lipoidica begins as asymptomatic papules that enlarge progressively over months to years. They can become pruritic or painful and often develop ulceration. Histopathology shows horizontal zones of palisading histiocytes with intervening necrobiosis. An inflammatory infiltrate containing plasma cells also may be present (Figure 4).

The Diagnosis: Perforating Rheumatoid Nodule

Perforating rheumatoid nodule (RN) is a variant of RN that demonstrates necrobiotic material extruding through the epidermis via the process of transepidermal elimination.¹ The necrobiotic material contains fibrin and often harbors karyorrhectic debris. The pathogenesis of RN remains unclear; possible mechanisms include a small vessel vasculitis or mechanical trauma inciting a localized aggregation of inflammatory products and rheumatoid factor complexes. This induces macrophage activation, fibrin deposition, and necrosis.² The majority of patients with RNs have detectable rheumatoid factor and anticyclic citrullinated protein in the blood.³ Rheumatoid nodules are the most common cutaneous manifestations of rheumatoid arthritis (RA) and will develop in 30% to 40% of RA patients.^4,5 They typically are associated with advanced RA but may precede the onset of clinically severe RA in 5% to 10% of patients.5 Rheumatoid nodules generally range in size from 2 mm to 5 cm and are slightly more prevalent in men than in women. They present as firm painless masses typically on the extensor surfaces of the hands and olecranon process but can occur over any tendinous or ligamentlike structure.^6,7 Perforating RNs are most common on areas subjected to pressure or repeated trauma, such as the sacrum.

The diagnosis usually is clinical; however, in cases of diagnostic uncertainty, RN can be distinguished by its histologic appearance. Rheumatoid nodules demonstrate granulomatous palisading necrobiosis with a central zone of highly eosinophilic fibrinoid necrobiosis surrounded by palisading mononuclear cells and an outer zone of granulation tissue. There may be a mixed chronic inflammatory infiltrate predominantly composed of lymphocytes and histiocytes in the background.

Rheumatoid nodules typically do not require treatment; however, perforation is known to increase the risk for infection, and surgical excision generally is indicated for prophylaxis against infection, though nodules may recur in the excision area.^1,3,8 Alternatively, disease-modifying antirheumatic drugs and intralesional corticosteroids may effectively reduce the size of RNs. The differential diagnosis for perforating RNs includes epithelioid sarcoma, perforating granuloma annulare, necrobiotic xanthogranuloma, and necrobiosis lipoidica.

Epithelioid sarcoma is a malignant soft tissue tumor typically found on the upper extremities of adolescent or young adult males. They usually present as hard tender nodules that commonly ulcerate. Epithelioid sarcoma makes up less than 1% of soft tissue sarcomas.⁹ Although rare, they present a diagnostic pitfall, as the histology may mimic an inflammatory palisaded granulomatous dermatitis similar to RN and granuloma annulare, thus a high index of suspicion is required to not overlook this aggressive malignancy. Histology is typified by nodular aggregates of epithelioid cells with abundant eosinophilic cytoplasm and often with central zones of necrosis (Figure 1). Epithelioid sarcoma displays immunoreactivity to cytokeratin, CD34, and epithelial membrane antigen, but loss of integrase interactor 1 expression. Cytologic abnormalities such as pleomorphism and hyperchromatism can be helpful in distinguishing between epithelioid sarcoma and RN.

Perforating granuloma annulare is a rare subtype of granuloma annulare that presents with flesh- to red-colored papules that develop central crust or scale. Perforating granuloma annulare composes approximately 5% of granuloma annulare cases. Perforating granuloma annulare can develop on any region of the body but has an affinity for the extensor surfaces of the extremities. It most frequently occurs in young women and rarely presents as a single lesion.¹⁰ Granuloma annulare typically is not associated with joint pain, and thus it differs from most cases of RNs. Histologically, it presents with an inflammatory palisading granuloma. There may be overlying epidermal thinning or parakeratosis, which can progress to perforation and extrusion of necrobiotic material. In comparison with RN, perforating granuloma annulare displays mucin deposition in the necrobiotic zones in lieu of fibrin (Figure 2).^10,11

Necrobiotic xanthogranuloma is a rare chronic form of non-Langerhans histiocytosis that characteristically presents with yellow or violaceous indurated plaques and nodules in a periorbital distribution. It often is associated with monoclonal gammopathy of IgG-κ. Lesions will ulcerate in 40% to 50% of patients.¹² The mean age at presentation is in the sixth decade of life, and it is moderately predominant in females.13 Histopathology demonstrates palisading granulomatous formations with a lymphoplasmacytic infiltrate and zones of necrobiosis in the mid dermis extending into the panniculus. Characteristic histologic features that are variably present in necrobiotic xanthogranuloma but typically absent in RN include neutrophilic debris, cholesterol clefts, and Touton or foreign body giant cells (Figure 3).¹³

Necrobiosis lipoidica is a rare chronic granulomatous disease characterized by well-demarcated, atrophic, yellow-brown plaques on the pretibial surfaces. It typically presents in the third decade of life in women, and most cases are associated with diabetes mellitus types 1 or 2 or autoimmune conditions.14 Necrobiosis lipoidica begins as asymptomatic papules that enlarge progressively over months to years. They can become pruritic or painful and often develop ulceration. Histopathology shows horizontal zones of palisading histiocytes with intervening necrobiosis. An inflammatory infiltrate containing plasma cells also may be present (Figure 4).

The Diagnosis: Perforating Rheumatoid Nodule

Perforating rheumatoid nodule (RN) is a variant of RN that demonstrates necrobiotic material extruding through the epidermis via the process of transepidermal elimination.¹ The necrobiotic material contains fibrin and often harbors karyorrhectic debris. The pathogenesis of RN remains unclear; possible mechanisms include a small vessel vasculitis or mechanical trauma inciting a localized aggregation of inflammatory products and rheumatoid factor complexes. This induces macrophage activation, fibrin deposition, and necrosis.² The majority of patients with RNs have detectable rheumatoid factor and anticyclic citrullinated protein in the blood.³ Rheumatoid nodules are the most common cutaneous manifestations of rheumatoid arthritis (RA) and will develop in 30% to 40% of RA patients.^4,5 They typically are associated with advanced RA but may precede the onset of clinically severe RA in 5% to 10% of patients.5 Rheumatoid nodules generally range in size from 2 mm to 5 cm and are slightly more prevalent in men than in women. They present as firm painless masses typically on the extensor surfaces of the hands and olecranon process but can occur over any tendinous or ligamentlike structure.^6,7 Perforating RNs are most common on areas subjected to pressure or repeated trauma, such as the sacrum.

The diagnosis usually is clinical; however, in cases of diagnostic uncertainty, RN can be distinguished by its histologic appearance. Rheumatoid nodules demonstrate granulomatous palisading necrobiosis with a central zone of highly eosinophilic fibrinoid necrobiosis surrounded by palisading mononuclear cells and an outer zone of granulation tissue. There may be a mixed chronic inflammatory infiltrate predominantly composed of lymphocytes and histiocytes in the background.

Rheumatoid nodules typically do not require treatment; however, perforation is known to increase the risk for infection, and surgical excision generally is indicated for prophylaxis against infection, though nodules may recur in the excision area.^1,3,8 Alternatively, disease-modifying antirheumatic drugs and intralesional corticosteroids may effectively reduce the size of RNs. The differential diagnosis for perforating RNs includes epithelioid sarcoma, perforating granuloma annulare, necrobiotic xanthogranuloma, and necrobiosis lipoidica.

Epithelioid sarcoma is a malignant soft tissue tumor typically found on the upper extremities of adolescent or young adult males. They usually present as hard tender nodules that commonly ulcerate. Epithelioid sarcoma makes up less than 1% of soft tissue sarcomas.⁹ Although rare, they present a diagnostic pitfall, as the histology may mimic an inflammatory palisaded granulomatous dermatitis similar to RN and granuloma annulare, thus a high index of suspicion is required to not overlook this aggressive malignancy. Histology is typified by nodular aggregates of epithelioid cells with abundant eosinophilic cytoplasm and often with central zones of necrosis (Figure 1). Epithelioid sarcoma displays immunoreactivity to cytokeratin, CD34, and epithelial membrane antigen, but loss of integrase interactor 1 expression. Cytologic abnormalities such as pleomorphism and hyperchromatism can be helpful in distinguishing between epithelioid sarcoma and RN.

Perforating granuloma annulare is a rare subtype of granuloma annulare that presents with flesh- to red-colored papules that develop central crust or scale. Perforating granuloma annulare composes approximately 5% of granuloma annulare cases. Perforating granuloma annulare can develop on any region of the body but has an affinity for the extensor surfaces of the extremities. It most frequently occurs in young women and rarely presents as a single lesion.¹⁰ Granuloma annulare typically is not associated with joint pain, and thus it differs from most cases of RNs. Histologically, it presents with an inflammatory palisading granuloma. There may be overlying epidermal thinning or parakeratosis, which can progress to perforation and extrusion of necrobiotic material. In comparison with RN, perforating granuloma annulare displays mucin deposition in the necrobiotic zones in lieu of fibrin (Figure 2).^10,11

Necrobiotic xanthogranuloma is a rare chronic form of non-Langerhans histiocytosis that characteristically presents with yellow or violaceous indurated plaques and nodules in a periorbital distribution. It often is associated with monoclonal gammopathy of IgG-κ. Lesions will ulcerate in 40% to 50% of patients.¹² The mean age at presentation is in the sixth decade of life, and it is moderately predominant in females.13 Histopathology demonstrates palisading granulomatous formations with a lymphoplasmacytic infiltrate and zones of necrobiosis in the mid dermis extending into the panniculus. Characteristic histologic features that are variably present in necrobiotic xanthogranuloma but typically absent in RN include neutrophilic debris, cholesterol clefts, and Touton or foreign body giant cells (Figure 3).¹³

Necrobiosis lipoidica is a rare chronic granulomatous disease characterized by well-demarcated, atrophic, yellow-brown plaques on the pretibial surfaces. It typically presents in the third decade of life in women, and most cases are associated with diabetes mellitus types 1 or 2 or autoimmune conditions.14 Necrobiosis lipoidica begins as asymptomatic papules that enlarge progressively over months to years. They can become pruritic or painful and often develop ulceration. Histopathology shows horizontal zones of palisading histiocytes with intervening necrobiosis. An inflammatory infiltrate containing plasma cells also may be present (Figure 4).

Medical education has seen major changes over the last decade. The allotted time for preclinical education has decreased from 24 months to 18 months or less at most institutions, with an increased focus on content associated with health care delivery and health system science.^1,2 Many schools now include at least some blended learning with online delivery of preclinical education.³ On the other hand, the clinical portion of medical education has remained largely unchanged prior to the COVID-19 pandemic, with the apprenticeship framework allowing the experienced physician to observe, mentor, and pass on practical knowledge so that the apprentice can one day gain independence after demonstrating adequate proficiency.⁴

With respect to dermatology education, skin disorders are in the top 5 reported reasons for visits to primary care⁵; however, a 2009 survey found that only 0.24% to 0.30% of medical schools’ curricula are spent on dermatology.⁶ Moreover, one institution found that fourth-year medical students received an average of 46.6% on a 15-item quiz designed to assess the ability to diagnose and treat common dermatologic conditions, and within that same cohort, 87.6% of students felt that they received inadequate training in dermatology during medical school.⁷

COVID-19 caused an unprecedented paradigm shift when medical schools throughout the country, including our own, canceled clinical rotations at the end of March 2020 to protect students and control the spread of infection. To enable clinical and preclinical learning to continue, institutions around the globe turned to either online learning or participation in telehealth as a substitute for clinical rotations.^8-10 At the Uniformed Services University of the Health Sciences (Bethesda, Maryland), one of the many online clinical courses offered included a distance learning (DL) dermatology course. Herein, we describe the results of a prospective study evaluating short-term information recall and comprehension as well as students’ confidence in their ability to apply course objectives over 3 months of an online DL dermatology course.

Methods

Between April and July 2020, 14 students at the Uniformed Services University of the Health Sciences (Table 1) enrolled in 1 of 3 four-week DL dermatology classes. The students independently completed the Basic Dermatology Curriculum, a set of online modules with demonstrated efficacy from the American Academy of Dermatology, over 4 weeks.¹¹ Additionally, students were instructed to review an hour of clinical dermatology images daily from online dermatology atlases and e-books accessed through our medical school’s virtual library. Optional Free Open Access Meducation resources also were provided. The course syllabus provided the students with clear expectations, links to the resources, and a recommended daily schedule.

An online video conferencing platform was utilized for an orientation session and 4 subsequent weekly 1.5-hour virtual meetings. The weekly DL meetings focused on a discussion of clinical images pertinent to the American Academy of Dermatology modules covered for the week. These interactive analytic sessions were referred to as Clinpic sessions. With instructor guidance, the students learned to describe images, and they provided differential diagnoses, workup, and treatments for various skin diseases. The virtual meetings included supplemental lectures detailing the use of teledermatology and laser therapy in the Military Health System and a journal review on the cutaneous manifestations of COVID-19.

A 40-question, image-based pretest and posttest utilized during clinical rotations evaluated knowledge recall and comprehension. A precourse and postcourse survey using a 5-point Likert scale (1=not confident; 5=extremely confident) assessed students’ confidence levels across course objectives: general knowledge of dermatology, working knowledge of teledermatology, ability to accurately describe skin lesions, generate sound differential diagnoses, and formulate a reasonable treatment plan. Statistical analysis was performed using free online statistical software at statskingdom.com.¹²

Results

All 14 student enrollees completed the precourse and postcourse tests and surveys. Pretest and posttest scores followed a normal distribution and therefore met criteria for utilization of a parametric test. The precourse test average of 67% (range, 40%–90%) improved to 84% postcourse (range, 70%–98%; P<.001; 95% CI, 11-23 by paired t test). Not surprisingly, the 2 students who had completed a dermatology rotation had higher average pretest and posttest scores (pretest, 87%; posttest, 94%). Students’ confidence with the course objectives were mostly at the somewhat confident level on the 5-point Likert scale precourse survey. By the end of the course, student survey responses increased to confident and very confident levels, corresponding to an overall improvement of 1.3 points (P<.001 by paired t test)(Table 2) when the mean of the survey results was aggregated across every question. Instructor evaluation of student performance mirrored student assessments.

 

 

Comment

The DL dermatology course succeeded in helping the enrolled students attain course objectives and offered a reasonable solution when in-person interaction was restricted. The students in the DL course made notable improvements in their dermatology knowledge and improved their communication, diagnosis, and management skills. Although a blended dermatology curriculum with e-learning combined with clinical experience has been shown to increase knowledge acquisition,^13,14 our results suggest that an online-only program also can increase comprehension as well as students’ confidence in their abilities.

A major challenge for the DL course was the lack of opportunity to perform common dermatology procedures. The addition of a hands-on skin procedure module would have been a great supplement to the course but was not possible due to social distancing guidelines during the COVID-19 pandemic. The small sample size and voluntary enrollment were limitations to this study.

Conclusion

Although the traditional dermatology rotation remains the gold standard for clinical instruction, a well-organized DL teaching environment allowed for a more controlled learning experience with a broader coverage of topics to include potentially greater exposure to rare skin disorders not typically encountered in everyday practice. A DL dermatology course may serve as an enduring curriculum for those who wish to learn dermatology more broadly and are not interested in performing skin procedures or direct patient exposure (eg, those pursuing non–primary care specialties, pathology, or radiology). It also may be attractive to students who have had a prior clinical dermatology rotation and desire a different learning experience with a wide coverage of topics.

Acknowledgments—The authors thank Thomas Darling, MD, PhD (Bethesda, Maryland), for coining the term Clinpic and providing critical feedback throughout the course. The authors also thank Sorana Raiciulescu, MS (Bethesda, Maryland), for assistance with the statistical analysis.

Medical education has seen major changes over the last decade. The allotted time for preclinical education has decreased from 24 months to 18 months or less at most institutions, with an increased focus on content associated with health care delivery and health system science.^1,2 Many schools now include at least some blended learning with online delivery of preclinical education.³ On the other hand, the clinical portion of medical education has remained largely unchanged prior to the COVID-19 pandemic, with the apprenticeship framework allowing the experienced physician to observe, mentor, and pass on practical knowledge so that the apprentice can one day gain independence after demonstrating adequate proficiency.⁴

With respect to dermatology education, skin disorders are in the top 5 reported reasons for visits to primary care⁵; however, a 2009 survey found that only 0.24% to 0.30% of medical schools’ curricula are spent on dermatology.⁶ Moreover, one institution found that fourth-year medical students received an average of 46.6% on a 15-item quiz designed to assess the ability to diagnose and treat common dermatologic conditions, and within that same cohort, 87.6% of students felt that they received inadequate training in dermatology during medical school.⁷

COVID-19 caused an unprecedented paradigm shift when medical schools throughout the country, including our own, canceled clinical rotations at the end of March 2020 to protect students and control the spread of infection. To enable clinical and preclinical learning to continue, institutions around the globe turned to either online learning or participation in telehealth as a substitute for clinical rotations.^8-10 At the Uniformed Services University of the Health Sciences (Bethesda, Maryland), one of the many online clinical courses offered included a distance learning (DL) dermatology course. Herein, we describe the results of a prospective study evaluating short-term information recall and comprehension as well as students’ confidence in their ability to apply course objectives over 3 months of an online DL dermatology course.

Methods

Between April and July 2020, 14 students at the Uniformed Services University of the Health Sciences (Table 1) enrolled in 1 of 3 four-week DL dermatology classes. The students independently completed the Basic Dermatology Curriculum, a set of online modules with demonstrated efficacy from the American Academy of Dermatology, over 4 weeks.¹¹ Additionally, students were instructed to review an hour of clinical dermatology images daily from online dermatology atlases and e-books accessed through our medical school’s virtual library. Optional Free Open Access Meducation resources also were provided. The course syllabus provided the students with clear expectations, links to the resources, and a recommended daily schedule.

An online video conferencing platform was utilized for an orientation session and 4 subsequent weekly 1.5-hour virtual meetings. The weekly DL meetings focused on a discussion of clinical images pertinent to the American Academy of Dermatology modules covered for the week. These interactive analytic sessions were referred to as Clinpic sessions. With instructor guidance, the students learned to describe images, and they provided differential diagnoses, workup, and treatments for various skin diseases. The virtual meetings included supplemental lectures detailing the use of teledermatology and laser therapy in the Military Health System and a journal review on the cutaneous manifestations of COVID-19.

A 40-question, image-based pretest and posttest utilized during clinical rotations evaluated knowledge recall and comprehension. A precourse and postcourse survey using a 5-point Likert scale (1=not confident; 5=extremely confident) assessed students’ confidence levels across course objectives: general knowledge of dermatology, working knowledge of teledermatology, ability to accurately describe skin lesions, generate sound differential diagnoses, and formulate a reasonable treatment plan. Statistical analysis was performed using free online statistical software at statskingdom.com.¹²

Results

All 14 student enrollees completed the precourse and postcourse tests and surveys. Pretest and posttest scores followed a normal distribution and therefore met criteria for utilization of a parametric test. The precourse test average of 67% (range, 40%–90%) improved to 84% postcourse (range, 70%–98%; P<.001; 95% CI, 11-23 by paired t test). Not surprisingly, the 2 students who had completed a dermatology rotation had higher average pretest and posttest scores (pretest, 87%; posttest, 94%). Students’ confidence with the course objectives were mostly at the somewhat confident level on the 5-point Likert scale precourse survey. By the end of the course, student survey responses increased to confident and very confident levels, corresponding to an overall improvement of 1.3 points (P<.001 by paired t test)(Table 2) when the mean of the survey results was aggregated across every question. Instructor evaluation of student performance mirrored student assessments.

 

 

Comment

The DL dermatology course succeeded in helping the enrolled students attain course objectives and offered a reasonable solution when in-person interaction was restricted. The students in the DL course made notable improvements in their dermatology knowledge and improved their communication, diagnosis, and management skills. Although a blended dermatology curriculum with e-learning combined with clinical experience has been shown to increase knowledge acquisition,^13,14 our results suggest that an online-only program also can increase comprehension as well as students’ confidence in their abilities.

A major challenge for the DL course was the lack of opportunity to perform common dermatology procedures. The addition of a hands-on skin procedure module would have been a great supplement to the course but was not possible due to social distancing guidelines during the COVID-19 pandemic. The small sample size and voluntary enrollment were limitations to this study.

Conclusion

Although the traditional dermatology rotation remains the gold standard for clinical instruction, a well-organized DL teaching environment allowed for a more controlled learning experience with a broader coverage of topics to include potentially greater exposure to rare skin disorders not typically encountered in everyday practice. A DL dermatology course may serve as an enduring curriculum for those who wish to learn dermatology more broadly and are not interested in performing skin procedures or direct patient exposure (eg, those pursuing non–primary care specialties, pathology, or radiology). It also may be attractive to students who have had a prior clinical dermatology rotation and desire a different learning experience with a wide coverage of topics.

Acknowledgments—The authors thank Thomas Darling, MD, PhD (Bethesda, Maryland), for coining the term Clinpic and providing critical feedback throughout the course. The authors also thank Sorana Raiciulescu, MS (Bethesda, Maryland), for assistance with the statistical analysis.

Medical education has seen major changes over the last decade. The allotted time for preclinical education has decreased from 24 months to 18 months or less at most institutions, with an increased focus on content associated with health care delivery and health system science.^1,2 Many schools now include at least some blended learning with online delivery of preclinical education.³ On the other hand, the clinical portion of medical education has remained largely unchanged prior to the COVID-19 pandemic, with the apprenticeship framework allowing the experienced physician to observe, mentor, and pass on practical knowledge so that the apprentice can one day gain independence after demonstrating adequate proficiency.⁴

With respect to dermatology education, skin disorders are in the top 5 reported reasons for visits to primary care⁵; however, a 2009 survey found that only 0.24% to 0.30% of medical schools’ curricula are spent on dermatology.⁶ Moreover, one institution found that fourth-year medical students received an average of 46.6% on a 15-item quiz designed to assess the ability to diagnose and treat common dermatologic conditions, and within that same cohort, 87.6% of students felt that they received inadequate training in dermatology during medical school.⁷

COVID-19 caused an unprecedented paradigm shift when medical schools throughout the country, including our own, canceled clinical rotations at the end of March 2020 to protect students and control the spread of infection. To enable clinical and preclinical learning to continue, institutions around the globe turned to either online learning or participation in telehealth as a substitute for clinical rotations.^8-10 At the Uniformed Services University of the Health Sciences (Bethesda, Maryland), one of the many online clinical courses offered included a distance learning (DL) dermatology course. Herein, we describe the results of a prospective study evaluating short-term information recall and comprehension as well as students’ confidence in their ability to apply course objectives over 3 months of an online DL dermatology course.

Methods

Between April and July 2020, 14 students at the Uniformed Services University of the Health Sciences (Table 1) enrolled in 1 of 3 four-week DL dermatology classes. The students independently completed the Basic Dermatology Curriculum, a set of online modules with demonstrated efficacy from the American Academy of Dermatology, over 4 weeks.¹¹ Additionally, students were instructed to review an hour of clinical dermatology images daily from online dermatology atlases and e-books accessed through our medical school’s virtual library. Optional Free Open Access Meducation resources also were provided. The course syllabus provided the students with clear expectations, links to the resources, and a recommended daily schedule.

An online video conferencing platform was utilized for an orientation session and 4 subsequent weekly 1.5-hour virtual meetings. The weekly DL meetings focused on a discussion of clinical images pertinent to the American Academy of Dermatology modules covered for the week. These interactive analytic sessions were referred to as Clinpic sessions. With instructor guidance, the students learned to describe images, and they provided differential diagnoses, workup, and treatments for various skin diseases. The virtual meetings included supplemental lectures detailing the use of teledermatology and laser therapy in the Military Health System and a journal review on the cutaneous manifestations of COVID-19.

A 40-question, image-based pretest and posttest utilized during clinical rotations evaluated knowledge recall and comprehension. A precourse and postcourse survey using a 5-point Likert scale (1=not confident; 5=extremely confident) assessed students’ confidence levels across course objectives: general knowledge of dermatology, working knowledge of teledermatology, ability to accurately describe skin lesions, generate sound differential diagnoses, and formulate a reasonable treatment plan. Statistical analysis was performed using free online statistical software at statskingdom.com.¹²

Results

All 14 student enrollees completed the precourse and postcourse tests and surveys. Pretest and posttest scores followed a normal distribution and therefore met criteria for utilization of a parametric test. The precourse test average of 67% (range, 40%–90%) improved to 84% postcourse (range, 70%–98%; P<.001; 95% CI, 11-23 by paired t test). Not surprisingly, the 2 students who had completed a dermatology rotation had higher average pretest and posttest scores (pretest, 87%; posttest, 94%). Students’ confidence with the course objectives were mostly at the somewhat confident level on the 5-point Likert scale precourse survey. By the end of the course, student survey responses increased to confident and very confident levels, corresponding to an overall improvement of 1.3 points (P<.001 by paired t test)(Table 2) when the mean of the survey results was aggregated across every question. Instructor evaluation of student performance mirrored student assessments.

 

 

Comment

The DL dermatology course succeeded in helping the enrolled students attain course objectives and offered a reasonable solution when in-person interaction was restricted. The students in the DL course made notable improvements in their dermatology knowledge and improved their communication, diagnosis, and management skills. Although a blended dermatology curriculum with e-learning combined with clinical experience has been shown to increase knowledge acquisition,^13,14 our results suggest that an online-only program also can increase comprehension as well as students’ confidence in their abilities.

A major challenge for the DL course was the lack of opportunity to perform common dermatology procedures. The addition of a hands-on skin procedure module would have been a great supplement to the course but was not possible due to social distancing guidelines during the COVID-19 pandemic. The small sample size and voluntary enrollment were limitations to this study.

Conclusion

Although the traditional dermatology rotation remains the gold standard for clinical instruction, a well-organized DL teaching environment allowed for a more controlled learning experience with a broader coverage of topics to include potentially greater exposure to rare skin disorders not typically encountered in everyday practice. A DL dermatology course may serve as an enduring curriculum for those who wish to learn dermatology more broadly and are not interested in performing skin procedures or direct patient exposure (eg, those pursuing non–primary care specialties, pathology, or radiology). It also may be attractive to students who have had a prior clinical dermatology rotation and desire a different learning experience with a wide coverage of topics.

Acknowledgments—The authors thank Thomas Darling, MD, PhD (Bethesda, Maryland), for coining the term Clinpic and providing critical feedback throughout the course. The authors also thank Sorana Raiciulescu, MS (Bethesda, Maryland), for assistance with the statistical analysis.

To the Editor:

Atopic dermatitis (AD) affects an estimated 7.2% of adults and 10.7% of children in the United States; however, AD might affect different races at a varying rate.¹ Compared to their European American counterparts, Asian/Pacific Islanders and African Americans are 7 and 3 times more likely, respectively, to be given a diagnosis of AD.²

Despite being disproportionately affected by AD, minority groups might be underrepresented in clinical trials of AD treatments.³ One explanation for this imbalance might be that ethnoracial representation differs across regions in the United States, perhaps in regions where clinical trials are conducted. Price et al³ investigated racial representation in clinical trials of AD globally and found that patients of color are consistently underrepresented.

Research on racial representation in clinical trials within the United States—on national and regional scales—is lacking from the current AD literature. We conducted a study to compare racial and ethnic disparities in AD clinical trials across regions of the United States. 

Using the ClinicalTrials.gov database (www.clinicaltrials.gov) of the National Library of Medicine, we identified clinical trials of AD treatments (encompassing phases 1 through 4) in the United States that were completed before March 14, 2021, with the earliest data from 2013. Search terms included atopic dermatitis, with an advanced search for interventional (clinical trials) and with results.

In total, 95 completed clinical trials were identified, of which 26 (27.4%) reported ethnoracial demographic data. One trial was excluded due to misrepresentation regarding the classification of individuals who identified as more than 1 racial category. Clinical trials for systemic treatments (7 [28%]) and topical treatments (18 [72%]) were identified.

All ethnoracial data were self-reported by trial participants based on US Food and Drug Administration guidelines for racial and ethnic categorization.⁴ Trial participants who identified ethnically as Hispanic or Latino might have been a part of any racial group. Only 7 of the 25 included clinical trials (28%) provided ethnic demographic data (Hispanic [Latino] or non-Hispanic); 72% of trials failed to report ethnicity. Ethnic data included in our analysis came from only the 7 clinical trials that included these data. International multicenter trials that included a US site were excluded.

Ultimately, the number of trials included in our analysis was 25, comprised of 2443 participants. Data were further organized by US geographic region (Northeast, Midwest, South, West, and multiregion trials [ie, conducted in ≥2 regions]). No AD clinical trials were conducted solely in the Midwest; it was only included within multiregion trials.

Compared to their representation in the 2019 US Census, most minority groups were overrepresented in clinical trials, while White individuals were underrepresented (eTable). The percentages of our findings on representation for race are as follows (US Census data are listed in parentheses for comparison⁵):

• White: 56.8% (72.5%)
• Black/African American: 28.3% (12.7%)
• Asian: 10.3% (5.5%)
• Multiracial: 1.1% (3.3%)
• Native Hawaiian or other Pacific Islander: 0.3% (0.2%)
• American Indian or Alaska Native: 0.2% (0.8%)
• Other: 0.5% (4.9%).

Our findings on representation for ethnicity are as follows (US Census data is listed in parentheses for comparison⁵):

• Hispanic or Latino: 21.4% (18.0%)

Although representation of Black/African American and Asian participants in clinical trials was higher than their representation in US Census data and representation of White participants was lower in clinical trials than their representation in census data, equal representation among all racial and ethnic groups is still lacking. A potential explanation for this finding might be that requirements for trial inclusion selected for more minority patients, given the propensity for greater severity of AD among those racial groups.² Another explanation might be that efforts to include minority patients in clinical trials are improving.

There were great differences in ethnoracial representation in clinical trials when regions within the United States were compared. Based on census population data by region, the West had the highest percentage (29.9%) of Hispanic or Latino residents; however, this group represented only 11.7% of participants in AD clinical trials in that region.⁵

The South had the greatest number of participants in AD clinical trials of any region, which was consistent with research findings on an association between severity of AD and heat.⁶ With a warmer climate correlating with an increased incidence of AD, it is possible that more people are willing to participate in clinical trials in the South.

The Midwest was the only region in which region-specific clinical trials were not conducted. Recent studies have shown that individuals with AD who live in the Midwest have comparatively less access to health care associated with AD treatment and are more likely to visit an emergency department because of AD than individuals in any other US region.⁷ This discrepancy highlights the need for increased access to resources and clinical trials focused on the treatment of AD in the Midwest.

In 1993, the National Institutes of Health Revitalization Act established a federal legislative mandate to encourage inclusion of women and people of color in clinical trials.⁸ During the last 2 decades, there have been improvements in ethnoracial reporting. A 2020 global study found that 81.1% of randomized controlled trials (phases 2 and 3) of AD treatments reported ethnoracial data.³

Equal representation in clinical trials allows for further investigation of the connection between race, AD severity, and treatment efficacy. Clinical trials need to have equal representation of ethnoracial categories across all regions of the United States. If one group is notably overrepresented, ethnoracial associations related to the treatment of AD might go undetected.⁹ Similarly, if representation is unequal, relationships of treatment efficacy within ethnoracial groups also might go undetected. None of the clinical trials that we analyzed investigated treatment efficacy by race, suggesting that there is a need for future research in this area.

It also is important to note that broad classifications of race and ethnicity are limiting and therefore overlook differences within ethnoracial categories. Although representation of minority patients in clinical trials for AD treatments is improving, we conclude that there remains a need for greater and equal representation of minority groups in clinical trials of AD treatments in the United States.

To the Editor:

Atopic dermatitis (AD) affects an estimated 7.2% of adults and 10.7% of children in the United States; however, AD might affect different races at a varying rate.¹ Compared to their European American counterparts, Asian/Pacific Islanders and African Americans are 7 and 3 times more likely, respectively, to be given a diagnosis of AD.²

Despite being disproportionately affected by AD, minority groups might be underrepresented in clinical trials of AD treatments.³ One explanation for this imbalance might be that ethnoracial representation differs across regions in the United States, perhaps in regions where clinical trials are conducted. Price et al³ investigated racial representation in clinical trials of AD globally and found that patients of color are consistently underrepresented.

Research on racial representation in clinical trials within the United States—on national and regional scales—is lacking from the current AD literature. We conducted a study to compare racial and ethnic disparities in AD clinical trials across regions of the United States. 

Using the ClinicalTrials.gov database (www.clinicaltrials.gov) of the National Library of Medicine, we identified clinical trials of AD treatments (encompassing phases 1 through 4) in the United States that were completed before March 14, 2021, with the earliest data from 2013. Search terms included atopic dermatitis, with an advanced search for interventional (clinical trials) and with results.

In total, 95 completed clinical trials were identified, of which 26 (27.4%) reported ethnoracial demographic data. One trial was excluded due to misrepresentation regarding the classification of individuals who identified as more than 1 racial category. Clinical trials for systemic treatments (7 [28%]) and topical treatments (18 [72%]) were identified.

All ethnoracial data were self-reported by trial participants based on US Food and Drug Administration guidelines for racial and ethnic categorization.⁴ Trial participants who identified ethnically as Hispanic or Latino might have been a part of any racial group. Only 7 of the 25 included clinical trials (28%) provided ethnic demographic data (Hispanic [Latino] or non-Hispanic); 72% of trials failed to report ethnicity. Ethnic data included in our analysis came from only the 7 clinical trials that included these data. International multicenter trials that included a US site were excluded.

Ultimately, the number of trials included in our analysis was 25, comprised of 2443 participants. Data were further organized by US geographic region (Northeast, Midwest, South, West, and multiregion trials [ie, conducted in ≥2 regions]). No AD clinical trials were conducted solely in the Midwest; it was only included within multiregion trials.

Compared to their representation in the 2019 US Census, most minority groups were overrepresented in clinical trials, while White individuals were underrepresented (eTable). The percentages of our findings on representation for race are as follows (US Census data are listed in parentheses for comparison⁵):

• White: 56.8% (72.5%)
• Black/African American: 28.3% (12.7%)
• Asian: 10.3% (5.5%)
• Multiracial: 1.1% (3.3%)
• Native Hawaiian or other Pacific Islander: 0.3% (0.2%)
• American Indian or Alaska Native: 0.2% (0.8%)
• Other: 0.5% (4.9%).

Our findings on representation for ethnicity are as follows (US Census data is listed in parentheses for comparison⁵):

• Hispanic or Latino: 21.4% (18.0%)

Although representation of Black/African American and Asian participants in clinical trials was higher than their representation in US Census data and representation of White participants was lower in clinical trials than their representation in census data, equal representation among all racial and ethnic groups is still lacking. A potential explanation for this finding might be that requirements for trial inclusion selected for more minority patients, given the propensity for greater severity of AD among those racial groups.² Another explanation might be that efforts to include minority patients in clinical trials are improving.

There were great differences in ethnoracial representation in clinical trials when regions within the United States were compared. Based on census population data by region, the West had the highest percentage (29.9%) of Hispanic or Latino residents; however, this group represented only 11.7% of participants in AD clinical trials in that region.⁵

The South had the greatest number of participants in AD clinical trials of any region, which was consistent with research findings on an association between severity of AD and heat.⁶ With a warmer climate correlating with an increased incidence of AD, it is possible that more people are willing to participate in clinical trials in the South.

The Midwest was the only region in which region-specific clinical trials were not conducted. Recent studies have shown that individuals with AD who live in the Midwest have comparatively less access to health care associated with AD treatment and are more likely to visit an emergency department because of AD than individuals in any other US region.⁷ This discrepancy highlights the need for increased access to resources and clinical trials focused on the treatment of AD in the Midwest.

In 1993, the National Institutes of Health Revitalization Act established a federal legislative mandate to encourage inclusion of women and people of color in clinical trials.⁸ During the last 2 decades, there have been improvements in ethnoracial reporting. A 2020 global study found that 81.1% of randomized controlled trials (phases 2 and 3) of AD treatments reported ethnoracial data.³

Equal representation in clinical trials allows for further investigation of the connection between race, AD severity, and treatment efficacy. Clinical trials need to have equal representation of ethnoracial categories across all regions of the United States. If one group is notably overrepresented, ethnoracial associations related to the treatment of AD might go undetected.⁹ Similarly, if representation is unequal, relationships of treatment efficacy within ethnoracial groups also might go undetected. None of the clinical trials that we analyzed investigated treatment efficacy by race, suggesting that there is a need for future research in this area.

It also is important to note that broad classifications of race and ethnicity are limiting and therefore overlook differences within ethnoracial categories. Although representation of minority patients in clinical trials for AD treatments is improving, we conclude that there remains a need for greater and equal representation of minority groups in clinical trials of AD treatments in the United States.

To the Editor:

Atopic dermatitis (AD) affects an estimated 7.2% of adults and 10.7% of children in the United States; however, AD might affect different races at a varying rate.¹ Compared to their European American counterparts, Asian/Pacific Islanders and African Americans are 7 and 3 times more likely, respectively, to be given a diagnosis of AD.²

Despite being disproportionately affected by AD, minority groups might be underrepresented in clinical trials of AD treatments.³ One explanation for this imbalance might be that ethnoracial representation differs across regions in the United States, perhaps in regions where clinical trials are conducted. Price et al³ investigated racial representation in clinical trials of AD globally and found that patients of color are consistently underrepresented.

Research on racial representation in clinical trials within the United States—on national and regional scales—is lacking from the current AD literature. We conducted a study to compare racial and ethnic disparities in AD clinical trials across regions of the United States. 

Using the ClinicalTrials.gov database (www.clinicaltrials.gov) of the National Library of Medicine, we identified clinical trials of AD treatments (encompassing phases 1 through 4) in the United States that were completed before March 14, 2021, with the earliest data from 2013. Search terms included atopic dermatitis, with an advanced search for interventional (clinical trials) and with results.

In total, 95 completed clinical trials were identified, of which 26 (27.4%) reported ethnoracial demographic data. One trial was excluded due to misrepresentation regarding the classification of individuals who identified as more than 1 racial category. Clinical trials for systemic treatments (7 [28%]) and topical treatments (18 [72%]) were identified.

All ethnoracial data were self-reported by trial participants based on US Food and Drug Administration guidelines for racial and ethnic categorization.⁴ Trial participants who identified ethnically as Hispanic or Latino might have been a part of any racial group. Only 7 of the 25 included clinical trials (28%) provided ethnic demographic data (Hispanic [Latino] or non-Hispanic); 72% of trials failed to report ethnicity. Ethnic data included in our analysis came from only the 7 clinical trials that included these data. International multicenter trials that included a US site were excluded.

Ultimately, the number of trials included in our analysis was 25, comprised of 2443 participants. Data were further organized by US geographic region (Northeast, Midwest, South, West, and multiregion trials [ie, conducted in ≥2 regions]). No AD clinical trials were conducted solely in the Midwest; it was only included within multiregion trials.

Compared to their representation in the 2019 US Census, most minority groups were overrepresented in clinical trials, while White individuals were underrepresented (eTable). The percentages of our findings on representation for race are as follows (US Census data are listed in parentheses for comparison⁵):

• White: 56.8% (72.5%)
• Black/African American: 28.3% (12.7%)
• Asian: 10.3% (5.5%)
• Multiracial: 1.1% (3.3%)
• Native Hawaiian or other Pacific Islander: 0.3% (0.2%)
• American Indian or Alaska Native: 0.2% (0.8%)
• Other: 0.5% (4.9%).

Our findings on representation for ethnicity are as follows (US Census data is listed in parentheses for comparison⁵):

• Hispanic or Latino: 21.4% (18.0%)

Although representation of Black/African American and Asian participants in clinical trials was higher than their representation in US Census data and representation of White participants was lower in clinical trials than their representation in census data, equal representation among all racial and ethnic groups is still lacking. A potential explanation for this finding might be that requirements for trial inclusion selected for more minority patients, given the propensity for greater severity of AD among those racial groups.² Another explanation might be that efforts to include minority patients in clinical trials are improving.

There were great differences in ethnoracial representation in clinical trials when regions within the United States were compared. Based on census population data by region, the West had the highest percentage (29.9%) of Hispanic or Latino residents; however, this group represented only 11.7% of participants in AD clinical trials in that region.⁵

The South had the greatest number of participants in AD clinical trials of any region, which was consistent with research findings on an association between severity of AD and heat.⁶ With a warmer climate correlating with an increased incidence of AD, it is possible that more people are willing to participate in clinical trials in the South.

The Midwest was the only region in which region-specific clinical trials were not conducted. Recent studies have shown that individuals with AD who live in the Midwest have comparatively less access to health care associated with AD treatment and are more likely to visit an emergency department because of AD than individuals in any other US region.⁷ This discrepancy highlights the need for increased access to resources and clinical trials focused on the treatment of AD in the Midwest.

In 1993, the National Institutes of Health Revitalization Act established a federal legislative mandate to encourage inclusion of women and people of color in clinical trials.⁸ During the last 2 decades, there have been improvements in ethnoracial reporting. A 2020 global study found that 81.1% of randomized controlled trials (phases 2 and 3) of AD treatments reported ethnoracial data.³

Equal representation in clinical trials allows for further investigation of the connection between race, AD severity, and treatment efficacy. Clinical trials need to have equal representation of ethnoracial categories across all regions of the United States. If one group is notably overrepresented, ethnoracial associations related to the treatment of AD might go undetected.⁹ Similarly, if representation is unequal, relationships of treatment efficacy within ethnoracial groups also might go undetected. None of the clinical trials that we analyzed investigated treatment efficacy by race, suggesting that there is a need for future research in this area.

It also is important to note that broad classifications of race and ethnicity are limiting and therefore overlook differences within ethnoracial categories. Although representation of minority patients in clinical trials for AD treatments is improving, we conclude that there remains a need for greater and equal representation of minority groups in clinical trials of AD treatments in the United States.