Pediatric Dermatology Consult - June 2018

 

The patient was diagnosed with granuloma annulare on the basis of history and clinical exam. A potassium hydroxide prep of skin scrapings was performed to rule out tinea corporis, and did not show evidence of fungal elements. The patient was treated with topical betamethasone with partial improvement.

First described as a “ringed eruption of the fingers” by Thomas Colcott Fox in 1895, granuloma annulare (GA) is a relatively common, benign, and self-limited condition whose precise etiology remains unclear. It is characterized commonly by pink to violaceous aciform or annular plaques on clinical examination. In some cases of GA, annular lesions are not present, or may be formed of grouped papules.

Courtesy Dr. Catalina Matiz

GA is a relatively common condition, accounting for up to 0.4% of dermatologists’ new patient visits according to one estimate.¹ GA is most common in children and young adults under 30 years, but has a bimodal distribution with a second, smaller peak of incidence in older adults aged 50-70 years.² In the younger group, localized GA is the most common presentation, whereas generalized GA is relatively more common in the older group. Across groups, there is a female predilection; approximately two-thirds of patients with GA are female.²

GA is characterized histologically by patchy interstitial lymphocytes and histiocytes palisading around mucin. Deep GA, an unusual subtype observed only in children, features a fibrin rather than a mucin core. This granulomatous picture is consistent with a Th1-mediated inflammatory process, and indeed, macrophage tumor necrosis factor production, as well as interleukin-2 and interferon-gamma production have been observed in GA. The reason for this exaggerated Th1 response is unknown, although in susceptible individuals trauma³ (an example of the Koebner phenomenon), arthropod assault,⁴ and herpes simplex infection⁵ (an example of Wolf isotopic response) all have been observed to trigger localized and/or generalized GA. Generalized GA has been associated with hyperlipidemia and the human leukocyte antigen–BW35 allele. GA has been described as a paraneoplastic eruption; atypical features such as associated pain or appearance in an uncharacteristic location often are present in such cases.^6,7

Courtesy Dr. Catalina Matiz

Although annular, erythematous plaques or patches on the dorsal hands or feet are the most common clinical manifestation of GA, a range of presentations exist. The lesions may be flesh-colored, faint pink, or violaceous. The lesions may include papules or plaques; in some cases, annular lesions may not be present. In children, subcutaneous or deep-dermal GA may resemble rheumatoid nodules. Some papular lesions may have central umbilication or papulation because of transepidermal elimination of mucin or collagen; in these cases, GA may be mistaken for molluscum contagiosum. However, despite these variations in clinical appearance, attention should be paid to symptomatology as GA is not pruritic.

Diagnosis of typical GA is clinical. If unusual features make you suspect tinea, leprosy, mycosis fungoides, or other annular lesions, then biopsy showing features typical of GA can reveal the correct diagnosis. Biopsy also can help to distinguish papular GA from warts or molluscum contagiosum. If extensive GA are present, then serum lipid testing for hypercholesterolemia or hypertriglyceridemia should be considered.

Other annular and raised lesions are on the differential for GA, but careful attention to the patient’s history and examination can clarify the diagnosis. Urticaria multiforme, a variant of annular urticaria, presents with numerous annular and polycyclic wheals, sometimes with central darkening that may be mistaken for necrosis. This patient did not present with polycyclic wheals. Furthermore, the lesions in urticaria multiforme are typically transient, with individual lesions lasting less than 24 hours, which was not the case with this patient. Wells syndrome, also known as eosinophilic cellulitis, is a condition marked by recurrent episodes of pruritus followed by appearance of edematous, painful, indurated, or edematous papules or plaques, although bullae and vesicles also may be present. The face and extremities are frequently involved and spontaneous resolution typically occurs in 2 months. Annular lesions are possible but papules, plaques, and nodules are more common in Wells syndrome. Annular elastolytic giant cell granuloma (AEGCG), also known as actinic granuloma and Miescher granuloma of the face, is an entity characterized clinically by chronic, persistent, sun-distributed, annular plaques typically seen in older women with significant sun damage. AEGCG is considered by some to be a variant of GA, but if this is the case, it is a distinct subtype with different epidemiologic, clinical, and histopathologic characteristics from GA. Interstitial granulomatous dermatitis is histologically and clinically distinct from GA, presenting as subtly erythematous cords or extensive annular or serpiginous plaques in the axilla, groin, buttocks, or chest, typically in adult patients with rheumatoid arthritis, reactive arthritis, psoriatic arthritis, or ankylosing spondylitis. Tinea corporis, the clinical manifestation of cutaneous dermatophyte infection, may be mistaken for granuloma annulare. However, tinea corporis lesions are scaly, whereas GA does not scale. Histologic examination of tinea corporis reveals hyphae, which are not present in GA.

GA lesions resolve spontaneously in a matter of months to years. Recurrence of lesions at previous sites is common, but recurrent lesions typically clear more quickly than initial lesions. As GA is not a dangerous condition, and as lesions are typically asymptomatic, reassurance and watchful waiting are the mainstays of treatment for most patients. Topical corticosteroids may be beneficial for patients with superficial lesions, whereas intralesional corticosteroids have been evaluated for deeper and thicker lesions. For patients with more extensive or distressing disease, UVA phototherapy appears to be effective for some patients. Treatment is often unsatisfying, and as a result a variety of treatments have been evaluated for treatment of GA, including surgical excision, cryotherapy, electrodesiccation, pulsed-dye laser, dapsone, niacinamide/nicotinamide, chloroquine, and isotretinoin, with varying results.^8,9 However, high-quality data supporting such treatments are lacking.

GA is a relatively common, idiopathic, benign skin disease with numerous annular and papular mimics. Absence of scale, pain, and significant pruritus are important clues to the diagnosis, and biopsy can be helpful when the diagnosis is unclear. Treatment, although not necessary, may be offered using any of a number of modalities. The most consistent and effective healer of GA, however, is time.

Mr. Kusari is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego, and the departments of dermatology and pediatrics, University of California, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. They reported having no conflicts of interest.

References

1. J Am Acad Dermatol. 1980 Sep;3(3):217-30.

2. J Am Acad Dermatol. 2016 Sep;75(3):457-65.

3. Dermatol Online J. 2013 Dec 16;19(12):20719.

4. Acta Derm Venereol. 2008;88(5):519-20.

5. J Cutan Med Surg. 2014 Nov;18(6):413-9.

6. South Med J. 1997 Oct;90(10):1056-9.

7. Am J Dermatopathol. 2003 Apr;25(2):113-6.

8. Am J Clin Dermatol. 2013 Aug;14(4):279-90.

9. Br J Dermatol. 1994 Apr;130(4):494-7.

 

The patient was diagnosed with granuloma annulare on the basis of history and clinical exam. A potassium hydroxide prep of skin scrapings was performed to rule out tinea corporis, and did not show evidence of fungal elements. The patient was treated with topical betamethasone with partial improvement.

First described as a “ringed eruption of the fingers” by Thomas Colcott Fox in 1895, granuloma annulare (GA) is a relatively common, benign, and self-limited condition whose precise etiology remains unclear. It is characterized commonly by pink to violaceous aciform or annular plaques on clinical examination. In some cases of GA, annular lesions are not present, or may be formed of grouped papules.

Courtesy Dr. Catalina Matiz

GA is a relatively common condition, accounting for up to 0.4% of dermatologists’ new patient visits according to one estimate.¹ GA is most common in children and young adults under 30 years, but has a bimodal distribution with a second, smaller peak of incidence in older adults aged 50-70 years.² In the younger group, localized GA is the most common presentation, whereas generalized GA is relatively more common in the older group. Across groups, there is a female predilection; approximately two-thirds of patients with GA are female.²

GA is characterized histologically by patchy interstitial lymphocytes and histiocytes palisading around mucin. Deep GA, an unusual subtype observed only in children, features a fibrin rather than a mucin core. This granulomatous picture is consistent with a Th1-mediated inflammatory process, and indeed, macrophage tumor necrosis factor production, as well as interleukin-2 and interferon-gamma production have been observed in GA. The reason for this exaggerated Th1 response is unknown, although in susceptible individuals trauma³ (an example of the Koebner phenomenon), arthropod assault,⁴ and herpes simplex infection⁵ (an example of Wolf isotopic response) all have been observed to trigger localized and/or generalized GA. Generalized GA has been associated with hyperlipidemia and the human leukocyte antigen–BW35 allele. GA has been described as a paraneoplastic eruption; atypical features such as associated pain or appearance in an uncharacteristic location often are present in such cases.^6,7

Courtesy Dr. Catalina Matiz

Although annular, erythematous plaques or patches on the dorsal hands or feet are the most common clinical manifestation of GA, a range of presentations exist. The lesions may be flesh-colored, faint pink, or violaceous. The lesions may include papules or plaques; in some cases, annular lesions may not be present. In children, subcutaneous or deep-dermal GA may resemble rheumatoid nodules. Some papular lesions may have central umbilication or papulation because of transepidermal elimination of mucin or collagen; in these cases, GA may be mistaken for molluscum contagiosum. However, despite these variations in clinical appearance, attention should be paid to symptomatology as GA is not pruritic.

Diagnosis of typical GA is clinical. If unusual features make you suspect tinea, leprosy, mycosis fungoides, or other annular lesions, then biopsy showing features typical of GA can reveal the correct diagnosis. Biopsy also can help to distinguish papular GA from warts or molluscum contagiosum. If extensive GA are present, then serum lipid testing for hypercholesterolemia or hypertriglyceridemia should be considered.

Other annular and raised lesions are on the differential for GA, but careful attention to the patient’s history and examination can clarify the diagnosis. Urticaria multiforme, a variant of annular urticaria, presents with numerous annular and polycyclic wheals, sometimes with central darkening that may be mistaken for necrosis. This patient did not present with polycyclic wheals. Furthermore, the lesions in urticaria multiforme are typically transient, with individual lesions lasting less than 24 hours, which was not the case with this patient. Wells syndrome, also known as eosinophilic cellulitis, is a condition marked by recurrent episodes of pruritus followed by appearance of edematous, painful, indurated, or edematous papules or plaques, although bullae and vesicles also may be present. The face and extremities are frequently involved and spontaneous resolution typically occurs in 2 months. Annular lesions are possible but papules, plaques, and nodules are more common in Wells syndrome. Annular elastolytic giant cell granuloma (AEGCG), also known as actinic granuloma and Miescher granuloma of the face, is an entity characterized clinically by chronic, persistent, sun-distributed, annular plaques typically seen in older women with significant sun damage. AEGCG is considered by some to be a variant of GA, but if this is the case, it is a distinct subtype with different epidemiologic, clinical, and histopathologic characteristics from GA. Interstitial granulomatous dermatitis is histologically and clinically distinct from GA, presenting as subtly erythematous cords or extensive annular or serpiginous plaques in the axilla, groin, buttocks, or chest, typically in adult patients with rheumatoid arthritis, reactive arthritis, psoriatic arthritis, or ankylosing spondylitis. Tinea corporis, the clinical manifestation of cutaneous dermatophyte infection, may be mistaken for granuloma annulare. However, tinea corporis lesions are scaly, whereas GA does not scale. Histologic examination of tinea corporis reveals hyphae, which are not present in GA.

GA lesions resolve spontaneously in a matter of months to years. Recurrence of lesions at previous sites is common, but recurrent lesions typically clear more quickly than initial lesions. As GA is not a dangerous condition, and as lesions are typically asymptomatic, reassurance and watchful waiting are the mainstays of treatment for most patients. Topical corticosteroids may be beneficial for patients with superficial lesions, whereas intralesional corticosteroids have been evaluated for deeper and thicker lesions. For patients with more extensive or distressing disease, UVA phototherapy appears to be effective for some patients. Treatment is often unsatisfying, and as a result a variety of treatments have been evaluated for treatment of GA, including surgical excision, cryotherapy, electrodesiccation, pulsed-dye laser, dapsone, niacinamide/nicotinamide, chloroquine, and isotretinoin, with varying results.^8,9 However, high-quality data supporting such treatments are lacking.

GA is a relatively common, idiopathic, benign skin disease with numerous annular and papular mimics. Absence of scale, pain, and significant pruritus are important clues to the diagnosis, and biopsy can be helpful when the diagnosis is unclear. Treatment, although not necessary, may be offered using any of a number of modalities. The most consistent and effective healer of GA, however, is time.

Mr. Kusari is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego, and the departments of dermatology and pediatrics, University of California, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. They reported having no conflicts of interest.

References

1. J Am Acad Dermatol. 1980 Sep;3(3):217-30.

2. J Am Acad Dermatol. 2016 Sep;75(3):457-65.

3. Dermatol Online J. 2013 Dec 16;19(12):20719.

4. Acta Derm Venereol. 2008;88(5):519-20.

5. J Cutan Med Surg. 2014 Nov;18(6):413-9.

6. South Med J. 1997 Oct;90(10):1056-9.

7. Am J Dermatopathol. 2003 Apr;25(2):113-6.

8. Am J Clin Dermatol. 2013 Aug;14(4):279-90.

9. Br J Dermatol. 1994 Apr;130(4):494-7.

 

The patient was diagnosed with granuloma annulare on the basis of history and clinical exam. A potassium hydroxide prep of skin scrapings was performed to rule out tinea corporis, and did not show evidence of fungal elements. The patient was treated with topical betamethasone with partial improvement.

First described as a “ringed eruption of the fingers” by Thomas Colcott Fox in 1895, granuloma annulare (GA) is a relatively common, benign, and self-limited condition whose precise etiology remains unclear. It is characterized commonly by pink to violaceous aciform or annular plaques on clinical examination. In some cases of GA, annular lesions are not present, or may be formed of grouped papules.

Courtesy Dr. Catalina Matiz

GA is a relatively common condition, accounting for up to 0.4% of dermatologists’ new patient visits according to one estimate.¹ GA is most common in children and young adults under 30 years, but has a bimodal distribution with a second, smaller peak of incidence in older adults aged 50-70 years.² In the younger group, localized GA is the most common presentation, whereas generalized GA is relatively more common in the older group. Across groups, there is a female predilection; approximately two-thirds of patients with GA are female.²

GA is characterized histologically by patchy interstitial lymphocytes and histiocytes palisading around mucin. Deep GA, an unusual subtype observed only in children, features a fibrin rather than a mucin core. This granulomatous picture is consistent with a Th1-mediated inflammatory process, and indeed, macrophage tumor necrosis factor production, as well as interleukin-2 and interferon-gamma production have been observed in GA. The reason for this exaggerated Th1 response is unknown, although in susceptible individuals trauma³ (an example of the Koebner phenomenon), arthropod assault,⁴ and herpes simplex infection⁵ (an example of Wolf isotopic response) all have been observed to trigger localized and/or generalized GA. Generalized GA has been associated with hyperlipidemia and the human leukocyte antigen–BW35 allele. GA has been described as a paraneoplastic eruption; atypical features such as associated pain or appearance in an uncharacteristic location often are present in such cases.^6,7

Courtesy Dr. Catalina Matiz

Although annular, erythematous plaques or patches on the dorsal hands or feet are the most common clinical manifestation of GA, a range of presentations exist. The lesions may be flesh-colored, faint pink, or violaceous. The lesions may include papules or plaques; in some cases, annular lesions may not be present. In children, subcutaneous or deep-dermal GA may resemble rheumatoid nodules. Some papular lesions may have central umbilication or papulation because of transepidermal elimination of mucin or collagen; in these cases, GA may be mistaken for molluscum contagiosum. However, despite these variations in clinical appearance, attention should be paid to symptomatology as GA is not pruritic.

Diagnosis of typical GA is clinical. If unusual features make you suspect tinea, leprosy, mycosis fungoides, or other annular lesions, then biopsy showing features typical of GA can reveal the correct diagnosis. Biopsy also can help to distinguish papular GA from warts or molluscum contagiosum. If extensive GA are present, then serum lipid testing for hypercholesterolemia or hypertriglyceridemia should be considered.

Other annular and raised lesions are on the differential for GA, but careful attention to the patient’s history and examination can clarify the diagnosis. Urticaria multiforme, a variant of annular urticaria, presents with numerous annular and polycyclic wheals, sometimes with central darkening that may be mistaken for necrosis. This patient did not present with polycyclic wheals. Furthermore, the lesions in urticaria multiforme are typically transient, with individual lesions lasting less than 24 hours, which was not the case with this patient. Wells syndrome, also known as eosinophilic cellulitis, is a condition marked by recurrent episodes of pruritus followed by appearance of edematous, painful, indurated, or edematous papules or plaques, although bullae and vesicles also may be present. The face and extremities are frequently involved and spontaneous resolution typically occurs in 2 months. Annular lesions are possible but papules, plaques, and nodules are more common in Wells syndrome. Annular elastolytic giant cell granuloma (AEGCG), also known as actinic granuloma and Miescher granuloma of the face, is an entity characterized clinically by chronic, persistent, sun-distributed, annular plaques typically seen in older women with significant sun damage. AEGCG is considered by some to be a variant of GA, but if this is the case, it is a distinct subtype with different epidemiologic, clinical, and histopathologic characteristics from GA. Interstitial granulomatous dermatitis is histologically and clinically distinct from GA, presenting as subtly erythematous cords or extensive annular or serpiginous plaques in the axilla, groin, buttocks, or chest, typically in adult patients with rheumatoid arthritis, reactive arthritis, psoriatic arthritis, or ankylosing spondylitis. Tinea corporis, the clinical manifestation of cutaneous dermatophyte infection, may be mistaken for granuloma annulare. However, tinea corporis lesions are scaly, whereas GA does not scale. Histologic examination of tinea corporis reveals hyphae, which are not present in GA.

GA lesions resolve spontaneously in a matter of months to years. Recurrence of lesions at previous sites is common, but recurrent lesions typically clear more quickly than initial lesions. As GA is not a dangerous condition, and as lesions are typically asymptomatic, reassurance and watchful waiting are the mainstays of treatment for most patients. Topical corticosteroids may be beneficial for patients with superficial lesions, whereas intralesional corticosteroids have been evaluated for deeper and thicker lesions. For patients with more extensive or distressing disease, UVA phototherapy appears to be effective for some patients. Treatment is often unsatisfying, and as a result a variety of treatments have been evaluated for treatment of GA, including surgical excision, cryotherapy, electrodesiccation, pulsed-dye laser, dapsone, niacinamide/nicotinamide, chloroquine, and isotretinoin, with varying results.^8,9 However, high-quality data supporting such treatments are lacking.

GA is a relatively common, idiopathic, benign skin disease with numerous annular and papular mimics. Absence of scale, pain, and significant pruritus are important clues to the diagnosis, and biopsy can be helpful when the diagnosis is unclear. Treatment, although not necessary, may be offered using any of a number of modalities. The most consistent and effective healer of GA, however, is time.

Mr. Kusari is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego, and the departments of dermatology and pediatrics, University of California, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. They reported having no conflicts of interest.

References

1. J Am Acad Dermatol. 1980 Sep;3(3):217-30.

2. J Am Acad Dermatol. 2016 Sep;75(3):457-65.

3. Dermatol Online J. 2013 Dec 16;19(12):20719.

4. Acta Derm Venereol. 2008;88(5):519-20.

5. J Cutan Med Surg. 2014 Nov;18(6):413-9.

6. South Med J. 1997 Oct;90(10):1056-9.

7. Am J Dermatopathol. 2003 Apr;25(2):113-6.

8. Am J Clin Dermatol. 2013 Aug;14(4):279-90.

9. Br J Dermatol. 1994 Apr;130(4):494-7.