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Derm Dx

What Are These Nail Changes That Appeared Simultaneously in 3-Year-Old Twins?

September 2017

The patients were 3-year-old identical twins, with simultaneous rapid onset of nail changes observed 2 weeks earlier. The nail changes began as asymptomatic white bands. The twins were born to healthy parents after an uncomplicated pregnancy and delivery. The only significant positive medical history was a flu-like syndrome with a palmoplantar eruption about 5 weeks prior to the nail changes. There is no family history of nail diseases or abnormalities. Dermatologic examination revealed transverse, band-like ridging of 5 nail plates in twin 1 and 8 nail plates in twin 2 (Figure 1). The grooves were 2 mm in width, and were at a similar distance (4 mm) in both children from the proximal nail fold (Figures 2 and 3). The toenails were unaffected in both patients. There were no signs of periungual inflammation. The potassium hydroxide test was negative for fungal elements. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, and a liver profile were normal.

What is Your Diagnosis?

To learn the answer, go to page 2

Diagnosis: Onychomadesis Following Hand-Foot-and-Mouth Disease

Beau lines are transverse, band-like depressions extending from one lateral edge of the nail to the other, affecting all nails at corresponding levels. Onychomadesis is considered an extreme form of Beau lines with subsequent separation of the proximal nail plate from the nail bed. They both fall along a spectrum of nail plate abnormalities secondary to temporary nail matrix arrest.1 Nail matrix arrest has been associated with a variety of dermatologic conditions, systemic illnesses, and drug exposures (Table 1).2-12

Beau lines and onychomadesis show strong associations with viral infections in childhood. More recently, varicella- and Gianotti-Crosti syndrome-related cases have been observed.8,9

Nail changes can affect all or some of the nails, both the fingernails and toenails, however, fingernails are more frequently affected. The severity of the nail changes varies depending on the underlying cause and its duration.2

Onychomadesis and Hand-Foot-and-Mouth Disease
Hand-foot-and-mouth disease is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands, feet, and in the oral cavity. The incidence of this disease has increased in last few years. The most common pathogens are coxsackievirus A10 and A16, and Enterovirus 71. Over the past several years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia, and North America.13

Hand-foot-and-mouth disease has been considered a benign disease of a self-limiting nature. A number of atypical cases of hand-foot-and-mouth disease with unusual morphology and/or localization of skin lesions have been described.14 The features of coxsackievirus A6 hand-foot-and-mouth disease are atypical and more severe than those seen in manifestations of the classic disease.15,16

Hand-foot-and-mouth disease followed by onychomadesis was first reported in 2000 in 5 children in Chicago.17 Since then, isolated cases and small case series have been described in Europe and Asia.18-20

It is unclear whether the nail matrix arrest resulted from an inflammation that spread from skin lesions around the nails, or whether viral infection impacted the general condition of the children. The detection of coxsackievirus in the shed nail fragments suggests that the viral replication itself may directly damage the nail matrix.21
 

Differential Diagnosis
Conditions that need to be considered in patients with horizontal nail ridges or discolorations include proximal subungual onychomycosis, onycholysis, and onychoschizia. Features that distinguish these and other conditions from onychomadesis are listed in Table 2. A key clinical finding that differentiates onychomadesis from other nail disorders is synchronous appearance of the nail changes.

Treatment
The condition usually resolves spontaneously within several weeks and without residual sequelae. An emollient may improve the nail surface texture.21

Our Patients
Upon further questioning, the mother reported that 7 weeks prior to the examination, the twins had a mild flu-like illness and a vesicular eruption on the palmar aspects of the hands, as well as the plantar surface of feet bilaterally, that resolved within several days. A diagnosis of hand-foot-and-mouth disease was made. Moreover, the mother reported close contact with a child with hand-foot-and-mouth disease 1 week before these symptoms developed.

During the follow up, 2 fingernails in twin 2 developed complete nail shedding (Figure 4). A complete spontaneous healing of the nails was observed after 2 months.

Figure 4. A follow-up visit revealed proximal nail plate detachment of the index finger.

Conclusion
Nail matrix arrest is a self-limited condition that can be associated with a variety of cutaneous and systemic conditions. The diagnosis should be made carefully, with consideration of the key clinical features including Beau lines in mild forms, and onychomadesis and nail shading in severe forms. Clinicians should be aware of this rare but benign complication of hand-foot-and-mouth disease to avoid unnecessary investigations.

Dr Damevska is dermatologist at Dermatology Clinic, Medical Faculty at the University “Ss.Cyril and Methodius” in Skopje, Republic of Macedonia.
Disclosure: The author reports no relevant financial relationships.

References
1. De Berker D. What do Beau’s lines mean? Int J Dermatol. 1994;33(8):545-546.
2. Hardin J, Haber RM. Onychomadesis: literature review. Br J Dermatol. 2015;172(3):592-596.
3. Tosti A, Piraccini BM, Camacho-Martinez F. Onychomadesis and pyogenic granuloma following cast immobilization. Arch Dermatol. 2001;137(2):231-232.
4. Grover C, Vohra S. Onychomadesis with lichen planus: an under-recognized manifestation. Indian J Dermatol. 2015;60(4):420.
5. Mehra A, Murphy RJ, Wilson BB. Idiopathic familial onychomadesis. J Am Acad Dermatol. 2000;43(2 Pt 2):349-350.
6. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426-2437.
7. Poretti A, Lips U, Belvedere M, Schmitt B. Onychomadesis: a rare side-effect of valproic acid medication? Pediatr Dermatol. 2009;26(6):749-50.
8. Podder I, Das A, Gharami RC. Onychomadesis following varicella infection: Is it a mere co-incidence? Indian J Dermatol. 2015;60(6):626-627.
9. Damevska K, Oncheva R, Oncheva S, Duma S. Onychomadesis following Gianotti-Crosti Syndrome. Glob Dermatol. 2016;3(1):243-244.
10. Piraccini BM, Rech G, Sisti A, Bellavista S. Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. J Am Acad Dermatol. 2010;63(1):172-174.
11. Acharya S, Balachandran C. Onychomadesis in stevens johnson syndrome. Indian J Dermatol Venereol Leprol. 1996;62(4):264-265.
12. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-425.
13. Hayman R, Shepherd M, Tarring C, Best E. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. J Paediatr Child Health. 2014;50(10):751-755.
14. Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol. 2013;5(2):203-209.
15. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19(12):20745.
16. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59(3):201-203.
17. Clementz GC, Mancini AJ. Nail matrix arrest following hand-foot-mouth disease: a report of five children. Pediatr Dermatol. 2000;17(1):7-11.
18. Bernier V, Labrèze C, Bury F, Taïeb A. Nail matrix arrest in the course of hand, foot and mouth disease. Eur J Pediatr. 2001;160(11):649-651.
19. Osterback R, Vuorinen T, Linna M, Susi P, Hyypiä T, Waris M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15(9):1485-1488.
20. Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26(2):280-283.
21. Bettoli V, Zauli S, Toni G, Virgili A. Onychomadesis following hand, foot, and mouth disease: a case report from Italy and review of the literature. Int J Dermatol. 2013;52(6):728-730.

The patients were 3-year-old identical twins, with simultaneous rapid onset of nail changes observed 2 weeks earlier. The nail changes began as asymptomatic white bands. The twins were born to healthy parents after an uncomplicated pregnancy and delivery. The only significant positive medical history was a flu-like syndrome with a palmoplantar eruption about 5 weeks prior to the nail changes. There is no family history of nail diseases or abnormalities. Dermatologic examination revealed transverse, band-like ridging of 5 nail plates in twin 1 and 8 nail plates in twin 2 (Figure 1). The grooves were 2 mm in width, and were at a similar distance (4 mm) in both children from the proximal nail fold (Figures 2 and 3). The toenails were unaffected in both patients. There were no signs of periungual inflammation. The potassium hydroxide test was negative for fungal elements. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, and a liver profile were normal.

What is Your Diagnosis?

 

Diagnosis: Onychomadesis Following Hand-Foot-and-Mouth Disease

Beau lines are transverse, band-like depressions extending from one lateral edge of the nail to the other, affecting all nails at corresponding levels. Onychomadesis is considered an extreme form of Beau lines with subsequent separation of the proximal nail plate from the nail bed. They both fall along a spectrum of nail plate abnormalities secondary to temporary nail matrix arrest.1 Nail matrix arrest has been associated with a variety of dermatologic conditions, systemic illnesses, and drug exposures (Table 1).2-12

Beau lines and onychomadesis show strong associations with viral infections in childhood. More recently, varicella- and Gianotti-Crosti syndrome-related cases have been observed.8,9

Nail changes can affect all or some of the nails, both the fingernails and toenails, however, fingernails are more frequently affected. The severity of the nail changes varies depending on the underlying cause and its duration.2

Onychomadesis and Hand-Foot-and-Mouth Disease
Hand-foot-and-mouth disease is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands, feet, and in the oral cavity. The incidence of this disease has increased in last few years. The most common pathogens are coxsackievirus A10 and A16, and Enterovirus 71. Over the past several years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia, and North America.13

Hand-foot-and-mouth disease has been considered a benign disease of a self-limiting nature. A number of atypical cases of hand-foot-and-mouth disease with unusual morphology and/or localization of skin lesions have been described.14 The features of coxsackievirus A6 hand-foot-and-mouth disease are atypical and more severe than those seen in manifestations of the classic disease.15,16

Hand-foot-and-mouth disease followed by onychomadesis was first reported in 2000 in 5 children in Chicago.17 Since then, isolated cases and small case series have been described in Europe and Asia.18-20

It is unclear whether the nail matrix arrest resulted from an inflammation that spread from skin lesions around the nails, or whether viral infection impacted the general condition of the children. The detection of coxsackievirus in the shed nail fragments suggests that the viral replication itself may directly damage the nail matrix.21
 

Differential Diagnosis
Conditions that need to be considered in patients with horizontal nail ridges or discolorations include proximal subungual onychomycosis, onycholysis, and onychoschizia. Features that distinguish these and other conditions from onychomadesis are listed in Table 2. A key clinical finding that differentiates onychomadesis from other nail disorders is synchronous appearance of the nail changes.

Treatment
The condition usually resolves spontaneously within several weeks and without residual sequelae. An emollient may improve the nail surface texture.21

Our Patients
Upon further questioning, the mother reported that 7 weeks prior to the examination, the twins had a mild flu-like illness and a vesicular eruption on the palmar aspects of the hands, as well as the plantar surface of feet bilaterally, that resolved within several days. A diagnosis of hand-foot-and-mouth disease was made. Moreover, the mother reported close contact with a child with hand-foot-and-mouth disease 1 week before these symptoms developed.

During the follow up, 2 fingernails in twin 2 developed complete nail shedding (Figure 4). A complete spontaneous healing of the nails was observed after 2 months.

Figure 4. A follow-up visit revealed proximal nail plate detachment of the index finger.

Conclusion
Nail matrix arrest is a self-limited condition that can be associated with a variety of cutaneous and systemic conditions. The diagnosis should be made carefully, with consideration of the key clinical features including Beau lines in mild forms, and onychomadesis and nail shading in severe forms. Clinicians should be aware of this rare but benign complication of hand-foot-and-mouth disease to avoid unnecessary investigations.

Dr Damevska is dermatologist at Dermatology Clinic, Medical Faculty at the University “Ss.Cyril and Methodius” in Skopje, Republic of Macedonia.
Disclosure: The author reports no relevant financial relationships.

References
1. De Berker D. What do Beau’s lines mean? Int J Dermatol. 1994;33(8):545-546.
2. Hardin J, Haber RM. Onychomadesis: literature review. Br J Dermatol. 2015;172(3):592-596.
3. Tosti A, Piraccini BM, Camacho-Martinez F. Onychomadesis and pyogenic granuloma following cast immobilization. Arch Dermatol. 2001;137(2):231-232.
4. Grover C, Vohra S. Onychomadesis with lichen planus: an under-recognized manifestation. Indian J Dermatol. 2015;60(4):420.
5. Mehra A, Murphy RJ, Wilson BB. Idiopathic familial onychomadesis. J Am Acad Dermatol. 2000;43(2 Pt 2):349-350.
6. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426-2437.
7. Poretti A, Lips U, Belvedere M, Schmitt B. Onychomadesis: a rare side-effect of valproic acid medication? Pediatr Dermatol. 2009;26(6):749-50.
8. Podder I, Das A, Gharami RC. Onychomadesis following varicella infection: Is it a mere co-incidence? Indian J Dermatol. 2015;60(6):626-627.
9. Damevska K, Oncheva R, Oncheva S, Duma S. Onychomadesis following Gianotti-Crosti Syndrome. Glob Dermatol. 2016;3(1):243-244.
10. Piraccini BM, Rech G, Sisti A, Bellavista S. Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. J Am Acad Dermatol. 2010;63(1):172-174.
11. Acharya S, Balachandran C. Onychomadesis in stevens johnson syndrome. Indian J Dermatol Venereol Leprol. 1996;62(4):264-265.
12. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-425.
13. Hayman R, Shepherd M, Tarring C, Best E. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. J Paediatr Child Health. 2014;50(10):751-755.
14. Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol. 2013;5(2):203-209.
15. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19(12):20745.
16. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59(3):201-203.
17. Clementz GC, Mancini AJ. Nail matrix arrest following hand-foot-mouth disease: a report of five children. Pediatr Dermatol. 2000;17(1):7-11.
18. Bernier V, Labrèze C, Bury F, Taïeb A. Nail matrix arrest in the course of hand, foot and mouth disease. Eur J Pediatr. 2001;160(11):649-651.
19. Osterback R, Vuorinen T, Linna M, Susi P, Hyypiä T, Waris M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15(9):1485-1488.
20. Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26(2):280-283.
21. Bettoli V, Zauli S, Toni G, Virgili A. Onychomadesis following hand, foot, and mouth disease: a case report from Italy and review of the literature. Int J Dermatol. 2013;52(6):728-730.

The patients were 3-year-old identical twins, with simultaneous rapid onset of nail changes observed 2 weeks earlier. The nail changes began as asymptomatic white bands. The twins were born to healthy parents after an uncomplicated pregnancy and delivery. The only significant positive medical history was a flu-like syndrome with a palmoplantar eruption about 5 weeks prior to the nail changes. There is no family history of nail diseases or abnormalities. Dermatologic examination revealed transverse, band-like ridging of 5 nail plates in twin 1 and 8 nail plates in twin 2 (Figure 1). The grooves were 2 mm in width, and were at a similar distance (4 mm) in both children from the proximal nail fold (Figures 2 and 3). The toenails were unaffected in both patients. There were no signs of periungual inflammation. The potassium hydroxide test was negative for fungal elements. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, and a liver profile were normal.

What is Your Diagnosis?

,

The patients were 3-year-old identical twins, with simultaneous rapid onset of nail changes observed 2 weeks earlier. The nail changes began as asymptomatic white bands. The twins were born to healthy parents after an uncomplicated pregnancy and delivery. The only significant positive medical history was a flu-like syndrome with a palmoplantar eruption about 5 weeks prior to the nail changes. There is no family history of nail diseases or abnormalities. Dermatologic examination revealed transverse, band-like ridging of 5 nail plates in twin 1 and 8 nail plates in twin 2 (Figure 1). The grooves were 2 mm in width, and were at a similar distance (4 mm) in both children from the proximal nail fold (Figures 2 and 3). The toenails were unaffected in both patients. There were no signs of periungual inflammation. The potassium hydroxide test was negative for fungal elements. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, and a liver profile were normal.

What is Your Diagnosis?

To learn the answer, go to page 2

Diagnosis: Onychomadesis Following Hand-Foot-and-Mouth Disease

Beau lines are transverse, band-like depressions extending from one lateral edge of the nail to the other, affecting all nails at corresponding levels. Onychomadesis is considered an extreme form of Beau lines with subsequent separation of the proximal nail plate from the nail bed. They both fall along a spectrum of nail plate abnormalities secondary to temporary nail matrix arrest.1 Nail matrix arrest has been associated with a variety of dermatologic conditions, systemic illnesses, and drug exposures (Table 1).2-12

Beau lines and onychomadesis show strong associations with viral infections in childhood. More recently, varicella- and Gianotti-Crosti syndrome-related cases have been observed.8,9

Nail changes can affect all or some of the nails, both the fingernails and toenails, however, fingernails are more frequently affected. The severity of the nail changes varies depending on the underlying cause and its duration.2

Onychomadesis and Hand-Foot-and-Mouth Disease
Hand-foot-and-mouth disease is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands, feet, and in the oral cavity. The incidence of this disease has increased in last few years. The most common pathogens are coxsackievirus A10 and A16, and Enterovirus 71. Over the past several years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia, and North America.13

Hand-foot-and-mouth disease has been considered a benign disease of a self-limiting nature. A number of atypical cases of hand-foot-and-mouth disease with unusual morphology and/or localization of skin lesions have been described.14 The features of coxsackievirus A6 hand-foot-and-mouth disease are atypical and more severe than those seen in manifestations of the classic disease.15,16

Hand-foot-and-mouth disease followed by onychomadesis was first reported in 2000 in 5 children in Chicago.17 Since then, isolated cases and small case series have been described in Europe and Asia.18-20

It is unclear whether the nail matrix arrest resulted from an inflammation that spread from skin lesions around the nails, or whether viral infection impacted the general condition of the children. The detection of coxsackievirus in the shed nail fragments suggests that the viral replication itself may directly damage the nail matrix.21
 

Differential Diagnosis
Conditions that need to be considered in patients with horizontal nail ridges or discolorations include proximal subungual onychomycosis, onycholysis, and onychoschizia. Features that distinguish these and other conditions from onychomadesis are listed in Table 2. A key clinical finding that differentiates onychomadesis from other nail disorders is synchronous appearance of the nail changes.

Treatment
The condition usually resolves spontaneously within several weeks and without residual sequelae. An emollient may improve the nail surface texture.21

Our Patients
Upon further questioning, the mother reported that 7 weeks prior to the examination, the twins had a mild flu-like illness and a vesicular eruption on the palmar aspects of the hands, as well as the plantar surface of feet bilaterally, that resolved within several days. A diagnosis of hand-foot-and-mouth disease was made. Moreover, the mother reported close contact with a child with hand-foot-and-mouth disease 1 week before these symptoms developed.

During the follow up, 2 fingernails in twin 2 developed complete nail shedding (Figure 4). A complete spontaneous healing of the nails was observed after 2 months.

Figure 4. A follow-up visit revealed proximal nail plate detachment of the index finger.

Conclusion
Nail matrix arrest is a self-limited condition that can be associated with a variety of cutaneous and systemic conditions. The diagnosis should be made carefully, with consideration of the key clinical features including Beau lines in mild forms, and onychomadesis and nail shading in severe forms. Clinicians should be aware of this rare but benign complication of hand-foot-and-mouth disease to avoid unnecessary investigations.

Dr Damevska is dermatologist at Dermatology Clinic, Medical Faculty at the University “Ss.Cyril and Methodius” in Skopje, Republic of Macedonia.
Disclosure: The author reports no relevant financial relationships.

References
1. De Berker D. What do Beau’s lines mean? Int J Dermatol. 1994;33(8):545-546.
2. Hardin J, Haber RM. Onychomadesis: literature review. Br J Dermatol. 2015;172(3):592-596.
3. Tosti A, Piraccini BM, Camacho-Martinez F. Onychomadesis and pyogenic granuloma following cast immobilization. Arch Dermatol. 2001;137(2):231-232.
4. Grover C, Vohra S. Onychomadesis with lichen planus: an under-recognized manifestation. Indian J Dermatol. 2015;60(4):420.
5. Mehra A, Murphy RJ, Wilson BB. Idiopathic familial onychomadesis. J Am Acad Dermatol. 2000;43(2 Pt 2):349-350.
6. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426-2437.
7. Poretti A, Lips U, Belvedere M, Schmitt B. Onychomadesis: a rare side-effect of valproic acid medication? Pediatr Dermatol. 2009;26(6):749-50.
8. Podder I, Das A, Gharami RC. Onychomadesis following varicella infection: Is it a mere co-incidence? Indian J Dermatol. 2015;60(6):626-627.
9. Damevska K, Oncheva R, Oncheva S, Duma S. Onychomadesis following Gianotti-Crosti Syndrome. Glob Dermatol. 2016;3(1):243-244.
10. Piraccini BM, Rech G, Sisti A, Bellavista S. Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. J Am Acad Dermatol. 2010;63(1):172-174.
11. Acharya S, Balachandran C. Onychomadesis in stevens johnson syndrome. Indian J Dermatol Venereol Leprol. 1996;62(4):264-265.
12. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-425.
13. Hayman R, Shepherd M, Tarring C, Best E. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. J Paediatr Child Health. 2014;50(10):751-755.
14. Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol. 2013;5(2):203-209.
15. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19(12):20745.
16. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59(3):201-203.
17. Clementz GC, Mancini AJ. Nail matrix arrest following hand-foot-mouth disease: a report of five children. Pediatr Dermatol. 2000;17(1):7-11.
18. Bernier V, Labrèze C, Bury F, Taïeb A. Nail matrix arrest in the course of hand, foot and mouth disease. Eur J Pediatr. 2001;160(11):649-651.
19. Osterback R, Vuorinen T, Linna M, Susi P, Hyypiä T, Waris M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15(9):1485-1488.
20. Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26(2):280-283.
21. Bettoli V, Zauli S, Toni G, Virgili A. Onychomadesis following hand, foot, and mouth disease: a case report from Italy and review of the literature. Int J Dermatol. 2013;52(6):728-730.

The patients were 3-year-old identical twins, with simultaneous rapid onset of nail changes observed 2 weeks earlier. The nail changes began as asymptomatic white bands. The twins were born to healthy parents after an uncomplicated pregnancy and delivery. The only significant positive medical history was a flu-like syndrome with a palmoplantar eruption about 5 weeks prior to the nail changes. There is no family history of nail diseases or abnormalities. Dermatologic examination revealed transverse, band-like ridging of 5 nail plates in twin 1 and 8 nail plates in twin 2 (Figure 1). The grooves were 2 mm in width, and were at a similar distance (4 mm) in both children from the proximal nail fold (Figures 2 and 3). The toenails were unaffected in both patients. There were no signs of periungual inflammation. The potassium hydroxide test was negative for fungal elements. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, and a liver profile were normal.

What is Your Diagnosis?

 

Diagnosis: Onychomadesis Following Hand-Foot-and-Mouth Disease

Beau lines are transverse, band-like depressions extending from one lateral edge of the nail to the other, affecting all nails at corresponding levels. Onychomadesis is considered an extreme form of Beau lines with subsequent separation of the proximal nail plate from the nail bed. They both fall along a spectrum of nail plate abnormalities secondary to temporary nail matrix arrest.1 Nail matrix arrest has been associated with a variety of dermatologic conditions, systemic illnesses, and drug exposures (Table 1).2-12

Beau lines and onychomadesis show strong associations with viral infections in childhood. More recently, varicella- and Gianotti-Crosti syndrome-related cases have been observed.8,9

Nail changes can affect all or some of the nails, both the fingernails and toenails, however, fingernails are more frequently affected. The severity of the nail changes varies depending on the underlying cause and its duration.2

Onychomadesis and Hand-Foot-and-Mouth Disease
Hand-foot-and-mouth disease is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands, feet, and in the oral cavity. The incidence of this disease has increased in last few years. The most common pathogens are coxsackievirus A10 and A16, and Enterovirus 71. Over the past several years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia, and North America.13

Hand-foot-and-mouth disease has been considered a benign disease of a self-limiting nature. A number of atypical cases of hand-foot-and-mouth disease with unusual morphology and/or localization of skin lesions have been described.14 The features of coxsackievirus A6 hand-foot-and-mouth disease are atypical and more severe than those seen in manifestations of the classic disease.15,16

Hand-foot-and-mouth disease followed by onychomadesis was first reported in 2000 in 5 children in Chicago.17 Since then, isolated cases and small case series have been described in Europe and Asia.18-20

It is unclear whether the nail matrix arrest resulted from an inflammation that spread from skin lesions around the nails, or whether viral infection impacted the general condition of the children. The detection of coxsackievirus in the shed nail fragments suggests that the viral replication itself may directly damage the nail matrix.21
 

Differential Diagnosis
Conditions that need to be considered in patients with horizontal nail ridges or discolorations include proximal subungual onychomycosis, onycholysis, and onychoschizia. Features that distinguish these and other conditions from onychomadesis are listed in Table 2. A key clinical finding that differentiates onychomadesis from other nail disorders is synchronous appearance of the nail changes.

Treatment
The condition usually resolves spontaneously within several weeks and without residual sequelae. An emollient may improve the nail surface texture.21

Our Patients
Upon further questioning, the mother reported that 7 weeks prior to the examination, the twins had a mild flu-like illness and a vesicular eruption on the palmar aspects of the hands, as well as the plantar surface of feet bilaterally, that resolved within several days. A diagnosis of hand-foot-and-mouth disease was made. Moreover, the mother reported close contact with a child with hand-foot-and-mouth disease 1 week before these symptoms developed.

During the follow up, 2 fingernails in twin 2 developed complete nail shedding (Figure 4). A complete spontaneous healing of the nails was observed after 2 months.

Figure 4. A follow-up visit revealed proximal nail plate detachment of the index finger.

Conclusion
Nail matrix arrest is a self-limited condition that can be associated with a variety of cutaneous and systemic conditions. The diagnosis should be made carefully, with consideration of the key clinical features including Beau lines in mild forms, and onychomadesis and nail shading in severe forms. Clinicians should be aware of this rare but benign complication of hand-foot-and-mouth disease to avoid unnecessary investigations.

Dr Damevska is dermatologist at Dermatology Clinic, Medical Faculty at the University “Ss.Cyril and Methodius” in Skopje, Republic of Macedonia.
Disclosure: The author reports no relevant financial relationships.

References
1. De Berker D. What do Beau’s lines mean? Int J Dermatol. 1994;33(8):545-546.
2. Hardin J, Haber RM. Onychomadesis: literature review. Br J Dermatol. 2015;172(3):592-596.
3. Tosti A, Piraccini BM, Camacho-Martinez F. Onychomadesis and pyogenic granuloma following cast immobilization. Arch Dermatol. 2001;137(2):231-232.
4. Grover C, Vohra S. Onychomadesis with lichen planus: an under-recognized manifestation. Indian J Dermatol. 2015;60(4):420.
5. Mehra A, Murphy RJ, Wilson BB. Idiopathic familial onychomadesis. J Am Acad Dermatol. 2000;43(2 Pt 2):349-350.
6. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426-2437.
7. Poretti A, Lips U, Belvedere M, Schmitt B. Onychomadesis: a rare side-effect of valproic acid medication? Pediatr Dermatol. 2009;26(6):749-50.
8. Podder I, Das A, Gharami RC. Onychomadesis following varicella infection: Is it a mere co-incidence? Indian J Dermatol. 2015;60(6):626-627.
9. Damevska K, Oncheva R, Oncheva S, Duma S. Onychomadesis following Gianotti-Crosti Syndrome. Glob Dermatol. 2016;3(1):243-244.
10. Piraccini BM, Rech G, Sisti A, Bellavista S. Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. J Am Acad Dermatol. 2010;63(1):172-174.
11. Acharya S, Balachandran C. Onychomadesis in stevens johnson syndrome. Indian J Dermatol Venereol Leprol. 1996;62(4):264-265.
12. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-425.
13. Hayman R, Shepherd M, Tarring C, Best E. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. J Paediatr Child Health. 2014;50(10):751-755.
14. Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol. 2013;5(2):203-209.
15. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19(12):20745.
16. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59(3):201-203.
17. Clementz GC, Mancini AJ. Nail matrix arrest following hand-foot-mouth disease: a report of five children. Pediatr Dermatol. 2000;17(1):7-11.
18. Bernier V, Labrèze C, Bury F, Taïeb A. Nail matrix arrest in the course of hand, foot and mouth disease. Eur J Pediatr. 2001;160(11):649-651.
19. Osterback R, Vuorinen T, Linna M, Susi P, Hyypiä T, Waris M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15(9):1485-1488.
20. Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26(2):280-283.
21. Bettoli V, Zauli S, Toni G, Virgili A. Onychomadesis following hand, foot, and mouth disease: a case report from Italy and review of the literature. Int J Dermatol. 2013;52(6):728-730.

 

Diagnosis: Onychomadesis Following Hand-Foot-and-Mouth Disease

Beau lines are transverse, band-like depressions extending from one lateral edge of the nail to the other, affecting all nails at corresponding levels. Onychomadesis is considered an extreme form of Beau lines with subsequent separation of the proximal nail plate from the nail bed. They both fall along a spectrum of nail plate abnormalities secondary to temporary nail matrix arrest.1 Nail matrix arrest has been associated with a variety of dermatologic conditions, systemic illnesses, and drug exposures (Table 1).2-12

Beau lines and onychomadesis show strong associations with viral infections in childhood. More recently, varicella- and Gianotti-Crosti syndrome-related cases have been observed.8,9

Nail changes can affect all or some of the nails, both the fingernails and toenails, however, fingernails are more frequently affected. The severity of the nail changes varies depending on the underlying cause and its duration.2

Onychomadesis and Hand-Foot-and-Mouth Disease
Hand-foot-and-mouth disease is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands, feet, and in the oral cavity. The incidence of this disease has increased in last few years. The most common pathogens are coxsackievirus A10 and A16, and Enterovirus 71. Over the past several years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia, and North America.13

Hand-foot-and-mouth disease has been considered a benign disease of a self-limiting nature. A number of atypical cases of hand-foot-and-mouth disease with unusual morphology and/or localization of skin lesions have been described.14 The features of coxsackievirus A6 hand-foot-and-mouth disease are atypical and more severe than those seen in manifestations of the classic disease.15,16

Hand-foot-and-mouth disease followed by onychomadesis was first reported in 2000 in 5 children in Chicago.17 Since then, isolated cases and small case series have been described in Europe and Asia.18-20

It is unclear whether the nail matrix arrest resulted from an inflammation that spread from skin lesions around the nails, or whether viral infection impacted the general condition of the children. The detection of coxsackievirus in the shed nail fragments suggests that the viral replication itself may directly damage the nail matrix.21
 

Differential Diagnosis
Conditions that need to be considered in patients with horizontal nail ridges or discolorations include proximal subungual onychomycosis, onycholysis, and onychoschizia. Features that distinguish these and other conditions from onychomadesis are listed in Table 2. A key clinical finding that differentiates onychomadesis from other nail disorders is synchronous appearance of the nail changes.

Treatment
The condition usually resolves spontaneously within several weeks and without residual sequelae. An emollient may improve the nail surface texture.21

Our Patients
Upon further questioning, the mother reported that 7 weeks prior to the examination, the twins had a mild flu-like illness and a vesicular eruption on the palmar aspects of the hands, as well as the plantar surface of feet bilaterally, that resolved within several days. A diagnosis of hand-foot-and-mouth disease was made. Moreover, the mother reported close contact with a child with hand-foot-and-mouth disease 1 week before these symptoms developed.

During the follow up, 2 fingernails in twin 2 developed complete nail shedding (Figure 4). A complete spontaneous healing of the nails was observed after 2 months.

Figure 4. A follow-up visit revealed proximal nail plate detachment of the index finger.

Conclusion
Nail matrix arrest is a self-limited condition that can be associated with a variety of cutaneous and systemic conditions. The diagnosis should be made carefully, with consideration of the key clinical features including Beau lines in mild forms, and onychomadesis and nail shading in severe forms. Clinicians should be aware of this rare but benign complication of hand-foot-and-mouth disease to avoid unnecessary investigations.

Dr Damevska is dermatologist at Dermatology Clinic, Medical Faculty at the University “Ss.Cyril and Methodius” in Skopje, Republic of Macedonia.
Disclosure: The author reports no relevant financial relationships.

References
1. De Berker D. What do Beau’s lines mean? Int J Dermatol. 1994;33(8):545-546.
2. Hardin J, Haber RM. Onychomadesis: literature review. Br J Dermatol. 2015;172(3):592-596.
3. Tosti A, Piraccini BM, Camacho-Martinez F. Onychomadesis and pyogenic granuloma following cast immobilization. Arch Dermatol. 2001;137(2):231-232.
4. Grover C, Vohra S. Onychomadesis with lichen planus: an under-recognized manifestation. Indian J Dermatol. 2015;60(4):420.
5. Mehra A, Murphy RJ, Wilson BB. Idiopathic familial onychomadesis. J Am Acad Dermatol. 2000;43(2 Pt 2):349-350.
6. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426-2437.
7. Poretti A, Lips U, Belvedere M, Schmitt B. Onychomadesis: a rare side-effect of valproic acid medication? Pediatr Dermatol. 2009;26(6):749-50.
8. Podder I, Das A, Gharami RC. Onychomadesis following varicella infection: Is it a mere co-incidence? Indian J Dermatol. 2015;60(6):626-627.
9. Damevska K, Oncheva R, Oncheva S, Duma S. Onychomadesis following Gianotti-Crosti Syndrome. Glob Dermatol. 2016;3(1):243-244.
10. Piraccini BM, Rech G, Sisti A, Bellavista S. Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. J Am Acad Dermatol. 2010;63(1):172-174.
11. Acharya S, Balachandran C. Onychomadesis in stevens johnson syndrome. Indian J Dermatol Venereol Leprol. 1996;62(4):264-265.
12. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-425.
13. Hayman R, Shepherd M, Tarring C, Best E. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. J Paediatr Child Health. 2014;50(10):751-755.
14. Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol. 2013;5(2):203-209.
15. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19(12):20745.
16. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59(3):201-203.
17. Clementz GC, Mancini AJ. Nail matrix arrest following hand-foot-mouth disease: a report of five children. Pediatr Dermatol. 2000;17(1):7-11.
18. Bernier V, Labrèze C, Bury F, Taïeb A. Nail matrix arrest in the course of hand, foot and mouth disease. Eur J Pediatr. 2001;160(11):649-651.
19. Osterback R, Vuorinen T, Linna M, Susi P, Hyypiä T, Waris M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15(9):1485-1488.
20. Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26(2):280-283.
21. Bettoli V, Zauli S, Toni G, Virgili A. Onychomadesis following hand, foot, and mouth disease: a case report from Italy and review of the literature. Int J Dermatol. 2013;52(6):728-730.