Pediatric Dermatology Consult - March 2016

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.