A Rare Association in Down Syndrome: Milialike Idiopathic Calcinosis Cutis and Palpebral Syringoma

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A Rare Association in Down Syndrome: Milialike Idiopathic Calcinosis Cutis and Palpebral Syringoma

To the Editor:
Down syndrome (DS) is associated with rare dermatological disorders, and the prevalence of some common dermatoses is greater in patients with DS. We report a case of milialike idiopathic calcinosis cutis (MICC) associated with syringomas in a patient with DS. We emphasize that MICC is one of the rare dermatoses associated with DS.

A 4-year-old girl with DS presented with a 4-mm, flesh-colored, regular-bordered, exophytic papular lesion on the left upper eyelid of 8 months' duration (Figure 1). It was clinically recognized as syringoma. On dermatologic examination of the patient, there also were 1- to 3-mm, round, whitish, painless, milialike papules on the dorsal surface of the hands and wrists (Figure 2). Some of these papules were surrounded by erythema. There was no sign of perforation. Her personal and family history were unremarkable.

Figure 1. A 4-mm exophytic papular lesion on the left upper eyelid.

Figure 2. Round whitish papules on the dorsal aspects of the hands and wrists (A) and milialike papules on the dorsal aspect of the hand (B).

Histopathologic examination of a biopsy from a  milialike lesion on the hand showed a hyperkeratotic epidermis. In the dermis there was a roundish calcific nodule surrounded by a fibrovascular rim. The patient's guardians refused a biopsy from the lesion on the eyelid.

Laboratory tests including serum vitamin D, thyroid and parathyroid hormone, calcium, phosphorus, and urinary calcium levels, as well as renal function tests, were within reference range. On the basis of these clinical and histopathological findings, the patient was diagnosed with MICC and palpebral syringoma.

Many dermatoses associated with DS have been reported including elastosis perforans serpiginosa, alopecia areata, and syringomas.1-3 Sano et al4 first described MICC and syringomas in a patient with DS in 1978. Milialike idiopathic calcinosis cutis is characterized by asymptomatic, millimetric, firm, round, whitish papules that are sometimes surrounded by erythema. These papules may show perforation leading to transepidermal elimination of calcium, similar to the transdermal elimination of elastic fibrils in elastosis perforans serpiginosa. Although MICC usually is described in acral sites of children with DS, it also is reported in adults without DS and on other parts of the body.5-7

The cause of MICC is unknown. One hypothesis of the development of MICC is an increase of the calcium content in the sweat leading to calcification of the acrosyringium.8 Milia are small keratin cysts that usually develop by occlusion of the hair follicle, sweat duct, or sebaceous duct. However, milia also can occur from occlusion of the eccrine ducts where syringomas originate.9 Therefore, syringomas can be seen in association with milia and calcium deposits.5,9-11

We believe that MICC in DS may be more common than usually recognized, as the lesions often are asymptomatic. It is important to differentiate MICC from other dermatological diseases such as molluscum contagiosum, verruca plana, milia, and inclusion cysts. Histopathology and dermoscopy could aid in the accurate diagnosis of MICC.

References
  1. Dourmishev A, Miteva L, Mitev V, et al. Cutaneous aspects of Down syndrome. Cutis. 2000;66:420-424.
  2. Madan V, Williams J, Lear JT. Dermatological manifestations of Down's syndrome. Clin Exp Dermatol. 2006;31:623-629.
  3. Schepis C, Barone C, Siragusa M, et al. An updated survey on skin conditions in Down syndrome. Dermatology. 2002;205:234-238.
  4. Sano T, Tate S, Ishikawa C. A case of Down's syndrome associated with syringoma, milia, and subepidermal calcified nodule. Jpn J Dermatol. 1978;88:740.
  5. Schepis C, Siragusa M, Palazzo R, et al. Perforating milia-like idiopathic calcinosis cutis and periorbital syringomas in a girl with Down syndrome. Pediatr Dermatol. 1994;11:258-260.
  6. Schepis C, Siragusa M, Palazzo R, et al. Milia like idiopathic calcinosis cutis: an unusual dermatosis associated with Down syndrome. Br J Dermatol. 1996;134:143-146.  
  7. Houtappel M, Leguit R, Sigurdsson V. Milia-like idiopathic calcinosis cutis in an adult without Down's syndrome. J Dermatol Case Rep. 2007;1:16-19.
  8. Eng AM, Mandrea E. Perforating calcinosis cutis presenting as milia. J Cutan Pathol. 1981;8:247-250.
  9. Wang KH, Chu JS, Lin YH, et al. Milium-like syringoma: a case study on histogenesis. J Cutan Pathol. 2004;31:336-340.
  10. Weiss E, Paez E, Greenberg AS, et al. Eruptive syringomas associated with milia. Int J Dermatol. 1995;34:193-195.
  11. Kim SJ, Won YH, Chun IK. Subepidermal calcified nodules and syringoma. J Eur Acad Dermatol Venereol. 1997;8:51-52.
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Drs. Turan, Yeşilova, and Tanrıkulu are from the Department of Dermatology, Faculty of Medicine, University of Harran, Turkey. Dr. Yurt is from the Department of Dermatology, Istanbul Education and Research Hospital, Turkey.

The authors report no conflict of interest.

Correspondence: Enver Turan, MD, Department of Dermatology, Faculty of Medicine, University of Harran, 63200-Sanliurfa, Turkey ([email protected]).

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Drs. Turan, Yeşilova, and Tanrıkulu are from the Department of Dermatology, Faculty of Medicine, University of Harran, Turkey. Dr. Yurt is from the Department of Dermatology, Istanbul Education and Research Hospital, Turkey.

The authors report no conflict of interest.

Correspondence: Enver Turan, MD, Department of Dermatology, Faculty of Medicine, University of Harran, 63200-Sanliurfa, Turkey ([email protected]).

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Drs. Turan, Yeşilova, and Tanrıkulu are from the Department of Dermatology, Faculty of Medicine, University of Harran, Turkey. Dr. Yurt is from the Department of Dermatology, Istanbul Education and Research Hospital, Turkey.

The authors report no conflict of interest.

Correspondence: Enver Turan, MD, Department of Dermatology, Faculty of Medicine, University of Harran, 63200-Sanliurfa, Turkey ([email protected]).

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To the Editor:
Down syndrome (DS) is associated with rare dermatological disorders, and the prevalence of some common dermatoses is greater in patients with DS. We report a case of milialike idiopathic calcinosis cutis (MICC) associated with syringomas in a patient with DS. We emphasize that MICC is one of the rare dermatoses associated with DS.

A 4-year-old girl with DS presented with a 4-mm, flesh-colored, regular-bordered, exophytic papular lesion on the left upper eyelid of 8 months' duration (Figure 1). It was clinically recognized as syringoma. On dermatologic examination of the patient, there also were 1- to 3-mm, round, whitish, painless, milialike papules on the dorsal surface of the hands and wrists (Figure 2). Some of these papules were surrounded by erythema. There was no sign of perforation. Her personal and family history were unremarkable.

Figure 1. A 4-mm exophytic papular lesion on the left upper eyelid.

Figure 2. Round whitish papules on the dorsal aspects of the hands and wrists (A) and milialike papules on the dorsal aspect of the hand (B).

Histopathologic examination of a biopsy from a  milialike lesion on the hand showed a hyperkeratotic epidermis. In the dermis there was a roundish calcific nodule surrounded by a fibrovascular rim. The patient's guardians refused a biopsy from the lesion on the eyelid.

Laboratory tests including serum vitamin D, thyroid and parathyroid hormone, calcium, phosphorus, and urinary calcium levels, as well as renal function tests, were within reference range. On the basis of these clinical and histopathological findings, the patient was diagnosed with MICC and palpebral syringoma.

Many dermatoses associated with DS have been reported including elastosis perforans serpiginosa, alopecia areata, and syringomas.1-3 Sano et al4 first described MICC and syringomas in a patient with DS in 1978. Milialike idiopathic calcinosis cutis is characterized by asymptomatic, millimetric, firm, round, whitish papules that are sometimes surrounded by erythema. These papules may show perforation leading to transepidermal elimination of calcium, similar to the transdermal elimination of elastic fibrils in elastosis perforans serpiginosa. Although MICC usually is described in acral sites of children with DS, it also is reported in adults without DS and on other parts of the body.5-7

The cause of MICC is unknown. One hypothesis of the development of MICC is an increase of the calcium content in the sweat leading to calcification of the acrosyringium.8 Milia are small keratin cysts that usually develop by occlusion of the hair follicle, sweat duct, or sebaceous duct. However, milia also can occur from occlusion of the eccrine ducts where syringomas originate.9 Therefore, syringomas can be seen in association with milia and calcium deposits.5,9-11

We believe that MICC in DS may be more common than usually recognized, as the lesions often are asymptomatic. It is important to differentiate MICC from other dermatological diseases such as molluscum contagiosum, verruca plana, milia, and inclusion cysts. Histopathology and dermoscopy could aid in the accurate diagnosis of MICC.

To the Editor:
Down syndrome (DS) is associated with rare dermatological disorders, and the prevalence of some common dermatoses is greater in patients with DS. We report a case of milialike idiopathic calcinosis cutis (MICC) associated with syringomas in a patient with DS. We emphasize that MICC is one of the rare dermatoses associated with DS.

A 4-year-old girl with DS presented with a 4-mm, flesh-colored, regular-bordered, exophytic papular lesion on the left upper eyelid of 8 months' duration (Figure 1). It was clinically recognized as syringoma. On dermatologic examination of the patient, there also were 1- to 3-mm, round, whitish, painless, milialike papules on the dorsal surface of the hands and wrists (Figure 2). Some of these papules were surrounded by erythema. There was no sign of perforation. Her personal and family history were unremarkable.

Figure 1. A 4-mm exophytic papular lesion on the left upper eyelid.

Figure 2. Round whitish papules on the dorsal aspects of the hands and wrists (A) and milialike papules on the dorsal aspect of the hand (B).

Histopathologic examination of a biopsy from a  milialike lesion on the hand showed a hyperkeratotic epidermis. In the dermis there was a roundish calcific nodule surrounded by a fibrovascular rim. The patient's guardians refused a biopsy from the lesion on the eyelid.

Laboratory tests including serum vitamin D, thyroid and parathyroid hormone, calcium, phosphorus, and urinary calcium levels, as well as renal function tests, were within reference range. On the basis of these clinical and histopathological findings, the patient was diagnosed with MICC and palpebral syringoma.

Many dermatoses associated with DS have been reported including elastosis perforans serpiginosa, alopecia areata, and syringomas.1-3 Sano et al4 first described MICC and syringomas in a patient with DS in 1978. Milialike idiopathic calcinosis cutis is characterized by asymptomatic, millimetric, firm, round, whitish papules that are sometimes surrounded by erythema. These papules may show perforation leading to transepidermal elimination of calcium, similar to the transdermal elimination of elastic fibrils in elastosis perforans serpiginosa. Although MICC usually is described in acral sites of children with DS, it also is reported in adults without DS and on other parts of the body.5-7

The cause of MICC is unknown. One hypothesis of the development of MICC is an increase of the calcium content in the sweat leading to calcification of the acrosyringium.8 Milia are small keratin cysts that usually develop by occlusion of the hair follicle, sweat duct, or sebaceous duct. However, milia also can occur from occlusion of the eccrine ducts where syringomas originate.9 Therefore, syringomas can be seen in association with milia and calcium deposits.5,9-11

We believe that MICC in DS may be more common than usually recognized, as the lesions often are asymptomatic. It is important to differentiate MICC from other dermatological diseases such as molluscum contagiosum, verruca plana, milia, and inclusion cysts. Histopathology and dermoscopy could aid in the accurate diagnosis of MICC.

References
  1. Dourmishev A, Miteva L, Mitev V, et al. Cutaneous aspects of Down syndrome. Cutis. 2000;66:420-424.
  2. Madan V, Williams J, Lear JT. Dermatological manifestations of Down's syndrome. Clin Exp Dermatol. 2006;31:623-629.
  3. Schepis C, Barone C, Siragusa M, et al. An updated survey on skin conditions in Down syndrome. Dermatology. 2002;205:234-238.
  4. Sano T, Tate S, Ishikawa C. A case of Down's syndrome associated with syringoma, milia, and subepidermal calcified nodule. Jpn J Dermatol. 1978;88:740.
  5. Schepis C, Siragusa M, Palazzo R, et al. Perforating milia-like idiopathic calcinosis cutis and periorbital syringomas in a girl with Down syndrome. Pediatr Dermatol. 1994;11:258-260.
  6. Schepis C, Siragusa M, Palazzo R, et al. Milia like idiopathic calcinosis cutis: an unusual dermatosis associated with Down syndrome. Br J Dermatol. 1996;134:143-146.  
  7. Houtappel M, Leguit R, Sigurdsson V. Milia-like idiopathic calcinosis cutis in an adult without Down's syndrome. J Dermatol Case Rep. 2007;1:16-19.
  8. Eng AM, Mandrea E. Perforating calcinosis cutis presenting as milia. J Cutan Pathol. 1981;8:247-250.
  9. Wang KH, Chu JS, Lin YH, et al. Milium-like syringoma: a case study on histogenesis. J Cutan Pathol. 2004;31:336-340.
  10. Weiss E, Paez E, Greenberg AS, et al. Eruptive syringomas associated with milia. Int J Dermatol. 1995;34:193-195.
  11. Kim SJ, Won YH, Chun IK. Subepidermal calcified nodules and syringoma. J Eur Acad Dermatol Venereol. 1997;8:51-52.
References
  1. Dourmishev A, Miteva L, Mitev V, et al. Cutaneous aspects of Down syndrome. Cutis. 2000;66:420-424.
  2. Madan V, Williams J, Lear JT. Dermatological manifestations of Down's syndrome. Clin Exp Dermatol. 2006;31:623-629.
  3. Schepis C, Barone C, Siragusa M, et al. An updated survey on skin conditions in Down syndrome. Dermatology. 2002;205:234-238.
  4. Sano T, Tate S, Ishikawa C. A case of Down's syndrome associated with syringoma, milia, and subepidermal calcified nodule. Jpn J Dermatol. 1978;88:740.
  5. Schepis C, Siragusa M, Palazzo R, et al. Perforating milia-like idiopathic calcinosis cutis and periorbital syringomas in a girl with Down syndrome. Pediatr Dermatol. 1994;11:258-260.
  6. Schepis C, Siragusa M, Palazzo R, et al. Milia like idiopathic calcinosis cutis: an unusual dermatosis associated with Down syndrome. Br J Dermatol. 1996;134:143-146.  
  7. Houtappel M, Leguit R, Sigurdsson V. Milia-like idiopathic calcinosis cutis in an adult without Down's syndrome. J Dermatol Case Rep. 2007;1:16-19.
  8. Eng AM, Mandrea E. Perforating calcinosis cutis presenting as milia. J Cutan Pathol. 1981;8:247-250.
  9. Wang KH, Chu JS, Lin YH, et al. Milium-like syringoma: a case study on histogenesis. J Cutan Pathol. 2004;31:336-340.
  10. Weiss E, Paez E, Greenberg AS, et al. Eruptive syringomas associated with milia. Int J Dermatol. 1995;34:193-195.
  11. Kim SJ, Won YH, Chun IK. Subepidermal calcified nodules and syringoma. J Eur Acad Dermatol Venereol. 1997;8:51-52.
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  • Down syndrome is associated with rare dermatological disorders and an increased prevalence of common dermatoses.
  • It is important to differentiate milialike idiopathic calcinosis cutis from other dermatological diseases using histopathology and dermoscopy.
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In Vivo Confocal Microscopy in the Diagnosis of Onychomycosis

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In Vivo Confocal Microscopy in the Diagnosis of Onychomycosis

To the Editor:

Onychomycosis is a common nail disease that frequently is caused by dermatophytes and is diagnosed by direct microscopy. Conventional diagnostic methods are often time consuming and can produce false-positive or false-negative results. We report a case of onychomycosis diagnosed by confocal microscopy and confirmed with routine potassium hydroxide (KOH) examination and fungal culture. Confocal microscopy is a reliable, practical, and noninvasive technique in the diagnosis of onychomycosis.

A 46-year-old woman presented with yellow-brown discoloration and dystrophy of the toenails (Figure 1) that had become worse over a 5-year period. She was otherwise healthy and had no other dermatologic problems. Examination revealed yellow-brown discoloration, subungual hyperkeratosis, and onycholysis of the toenails. Clinically, a diagnosis of onychomycosis was made. Potassium hydroxide examination of a scraping from the subungual region showed fungal elements. Trichophyton rubrum on Sabouraud dextrose agar was determined.

Figure 1. Onycholysis and onychodystrophy affecting the toes.

Figure 2. In vivo confocal image of hyphae (arrows).

We performed both in vivo and in vitro confocal laser scanning microscopic examination of the nail of the right great toe (Figure 2). For the diagnosis of onychomycosis in our case, we used a multilaser reflectance confocal microscope (RCM) with a wavelength of 786 nm. In vivo confocal microscopy of the nail revealed branching hyphae just below the surface of the nail plate. Hyphae were seen as refractile, bright, linear structures along the laminates of the nail.

Onychomycosis is a common condition affecting 5.5% of the population worldwide and representing 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.1,2 There are many methods available to confirm the clinical diagnosis of onychomycosis by detecting the causative organisms. Direct microscopic examination of the scraping with a KOH culture, histopathologic assessment with periodic acid–Schiff staining, immunofluorescence analysis with calcofluor white staining, enzyme analysis, and polymerase chain reaction can be used for diagnosis of fungal infections. The most frequently used diagnostic method for onychomycosis is KOH examination of the scraping; however, fungal culture and histopathologic examination also can be used in cases having diagnostic difficulties.1,3,4 There are many studies comparing the efficacies of these methods in the literature.5-9

The causative fungal agent should be determined with at least 1 laboratory method due to the high cost, long duration, and serious potential adverse effects of systemic antifungal treatment. Direct microscopic examination with KOH in the diagnosis of onychomycosis is simple, fast, and inexpensive. However, inadequate material, using crystallized KOH for hydrolysis, insufficient or too much hydrolysis of scrapings, inappropriate staining, and not scanning all areas in the microscopy produce false-negative results. Similarly, secondary contamination of hair, cotton, yarn, or air bubbles mimicking fungal structures can cause false-positive results.9,10

Fungal culture is another diagnostic method that is accepted as the gold standard for diagnosis of onychomycosis.9 However, fungal cultures were positive in only 43% to 50% of all cases of onychomycosis that were diagnosed with other methods,11,12 which may be due to the loss of viability and ability of the fungi to grow in culture media during the transport. A major advantage of fungal culture is that the fungal agent can be classified as dermatophyte, nondermatophyte, mold, or yeast. However, culture does determine if the growing fungi is contamination or the real pathogen. Moreover, it is necessary to wait 3 to 4 weeks for culture results. For nondermatophyte fungi this time may be much longer.12

In vivo RCM is a noninvasive imaging method that allows optical en face sectioning of the living tissue with high resolution. Currently, RCM has a wide range of applications, such as the evaluation of both benign and malignant skin lesions in clinical dermatology.13

In vivo RCM was used first by Hongcharu et al.14 The diagnoses of onychomycosis and fungal hyphae were shown both in vivo and in vitro.14 The sensitivity and specificity of confocal examination in the diagnosis of onychomycosis is not known yet. Large clinical trials are needed to assess the sensitivity and specificity of this method in diagnosing fungal infections.

Onychomycosis is a contagious infectious disease characterized by hyphae proliferation in the nail plate. Definitive diagnosis is necessary before treatment because onychomycosis can be mistaken for many infectious or noninfectious skin diseases with nail involvement. Conventional methods are time consuming, laborious, and less reliable. Instead of high-cost procedures, in vivo confocal microscopic examination can be a rapid and reliable diagnostic method for onychomycosis in the near future.

References

1. Singal A, Khanna D. Onychomycosis: diagnosis and management. Indian J Dermatol Venereol Leprol. 2011;77:659-672.

2. Kaur R, Kashyap B, Bhalla P. Onychomycosis—epidemiology, diagnosis and management. Indian J Med Microbiol. 2008;26:108-116.

3. Richardson MD. Diagnosis and pathogenesis of dermatophyte infections. Br J Clin Pract Suppl. 1990;71:98-102.

4. Jensen RH, Arendrup MC. Molecular diagnosis of dermato-phyte infections. Curr Opin Infect Dis. 2012;25:126-134.

5. Weinberg JM, Koestenblatt EK, Tutrone WD, et al. Comparison of diagnostic methods in the evaluation of onychomycosis. J Am Acad Dermatol. 2003;49:193-197.

6. Gianni C, Morelli V, Cerri A, et al. Usefulness of histological examination for the diagnosis of onychomycosis. Dermatology. 2001;202:283-288.

7. Machler BC, Kirsner RS, Elgart GW. Routine histologic examination for the diagnosis of onychomycosis: an evaluation of sensitivity and specificity. Cutis. 1998;61:217-219.

8. Wilsmann-Theis D, Sareika F, Bieber T, et al. New reasons for histopathological nail-clipping examination in the diagnosis of onychomycosis. J Eur Acad Dermatol Venereol. 2011;25:235-237.

9. Reisberger EM, Abels C, Landthaler M, et al. Histopathological diagnosis of onychomycosis by periodic acid-Schiff-stained nail clippings. Br J Dermatol. 2003;148:749-754.

10. Shemer A, Trau H, Davidovici B, et al. Collection of fungi samples from nails: comparative study of curettage and drilling techniques. J Eur Acad Dermatol Venereol. 2008;22:182-185.

11. Daniel CR 3rd, Elewski BE. The diagnosis of nail fungus infection revisited. Arch Dermatol. 2000;136:1162-1164.

12. Borkowski P, Williams M, Holewinski J, et al. Onychomycosis: an analysis of 50 cases and a comparison of diagnostic techniques. J Am Podiatr Med Assoc. 2001;91:351-355.

13. Rajadhyaksha M, Gonzalez S, Zavislan JM, et al. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol. 1999;113:293-303.

14. Hongcharu W, Dwyer P, Gonzalez S, et al. Confirmation of onychomycosis by in vivo confocal microscopy. J Am Acad Dermatol. 2000;42(2, pt 1):214-216.

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Dr. Turan is from the Department of Dermatology, University of Harran, Sanliurfa, Turkey. Drs. Yurt, Gurel, and Erdemir are from the Department of Dermatology, Istanbul Education and Research Hospital, Turkey.

The authors report no conflict of interest.

Correspondence: Enver Turan, MD, University of Harran, Department of Dermatology, 63200-Sanliurfa, Turkey ([email protected]).

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The authors report no conflict of interest.

Correspondence: Enver Turan, MD, University of Harran, Department of Dermatology, 63200-Sanliurfa, Turkey ([email protected]).

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Enver Turan, MD; Nurdan Yurt, MD; Mehmet Salih Gurel, MD; Asli Turgut Erdemir, MD

Dr. Turan is from the Department of Dermatology, University of Harran, Sanliurfa, Turkey. Drs. Yurt, Gurel, and Erdemir are from the Department of Dermatology, Istanbul Education and Research Hospital, Turkey.

The authors report no conflict of interest.

Correspondence: Enver Turan, MD, University of Harran, Department of Dermatology, 63200-Sanliurfa, Turkey ([email protected]).

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To the Editor:

Onychomycosis is a common nail disease that frequently is caused by dermatophytes and is diagnosed by direct microscopy. Conventional diagnostic methods are often time consuming and can produce false-positive or false-negative results. We report a case of onychomycosis diagnosed by confocal microscopy and confirmed with routine potassium hydroxide (KOH) examination and fungal culture. Confocal microscopy is a reliable, practical, and noninvasive technique in the diagnosis of onychomycosis.

A 46-year-old woman presented with yellow-brown discoloration and dystrophy of the toenails (Figure 1) that had become worse over a 5-year period. She was otherwise healthy and had no other dermatologic problems. Examination revealed yellow-brown discoloration, subungual hyperkeratosis, and onycholysis of the toenails. Clinically, a diagnosis of onychomycosis was made. Potassium hydroxide examination of a scraping from the subungual region showed fungal elements. Trichophyton rubrum on Sabouraud dextrose agar was determined.

Figure 1. Onycholysis and onychodystrophy affecting the toes.

Figure 2. In vivo confocal image of hyphae (arrows).

We performed both in vivo and in vitro confocal laser scanning microscopic examination of the nail of the right great toe (Figure 2). For the diagnosis of onychomycosis in our case, we used a multilaser reflectance confocal microscope (RCM) with a wavelength of 786 nm. In vivo confocal microscopy of the nail revealed branching hyphae just below the surface of the nail plate. Hyphae were seen as refractile, bright, linear structures along the laminates of the nail.

Onychomycosis is a common condition affecting 5.5% of the population worldwide and representing 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.1,2 There are many methods available to confirm the clinical diagnosis of onychomycosis by detecting the causative organisms. Direct microscopic examination of the scraping with a KOH culture, histopathologic assessment with periodic acid–Schiff staining, immunofluorescence analysis with calcofluor white staining, enzyme analysis, and polymerase chain reaction can be used for diagnosis of fungal infections. The most frequently used diagnostic method for onychomycosis is KOH examination of the scraping; however, fungal culture and histopathologic examination also can be used in cases having diagnostic difficulties.1,3,4 There are many studies comparing the efficacies of these methods in the literature.5-9

The causative fungal agent should be determined with at least 1 laboratory method due to the high cost, long duration, and serious potential adverse effects of systemic antifungal treatment. Direct microscopic examination with KOH in the diagnosis of onychomycosis is simple, fast, and inexpensive. However, inadequate material, using crystallized KOH for hydrolysis, insufficient or too much hydrolysis of scrapings, inappropriate staining, and not scanning all areas in the microscopy produce false-negative results. Similarly, secondary contamination of hair, cotton, yarn, or air bubbles mimicking fungal structures can cause false-positive results.9,10

Fungal culture is another diagnostic method that is accepted as the gold standard for diagnosis of onychomycosis.9 However, fungal cultures were positive in only 43% to 50% of all cases of onychomycosis that were diagnosed with other methods,11,12 which may be due to the loss of viability and ability of the fungi to grow in culture media during the transport. A major advantage of fungal culture is that the fungal agent can be classified as dermatophyte, nondermatophyte, mold, or yeast. However, culture does determine if the growing fungi is contamination or the real pathogen. Moreover, it is necessary to wait 3 to 4 weeks for culture results. For nondermatophyte fungi this time may be much longer.12

In vivo RCM is a noninvasive imaging method that allows optical en face sectioning of the living tissue with high resolution. Currently, RCM has a wide range of applications, such as the evaluation of both benign and malignant skin lesions in clinical dermatology.13

In vivo RCM was used first by Hongcharu et al.14 The diagnoses of onychomycosis and fungal hyphae were shown both in vivo and in vitro.14 The sensitivity and specificity of confocal examination in the diagnosis of onychomycosis is not known yet. Large clinical trials are needed to assess the sensitivity and specificity of this method in diagnosing fungal infections.

Onychomycosis is a contagious infectious disease characterized by hyphae proliferation in the nail plate. Definitive diagnosis is necessary before treatment because onychomycosis can be mistaken for many infectious or noninfectious skin diseases with nail involvement. Conventional methods are time consuming, laborious, and less reliable. Instead of high-cost procedures, in vivo confocal microscopic examination can be a rapid and reliable diagnostic method for onychomycosis in the near future.

To the Editor:

Onychomycosis is a common nail disease that frequently is caused by dermatophytes and is diagnosed by direct microscopy. Conventional diagnostic methods are often time consuming and can produce false-positive or false-negative results. We report a case of onychomycosis diagnosed by confocal microscopy and confirmed with routine potassium hydroxide (KOH) examination and fungal culture. Confocal microscopy is a reliable, practical, and noninvasive technique in the diagnosis of onychomycosis.

A 46-year-old woman presented with yellow-brown discoloration and dystrophy of the toenails (Figure 1) that had become worse over a 5-year period. She was otherwise healthy and had no other dermatologic problems. Examination revealed yellow-brown discoloration, subungual hyperkeratosis, and onycholysis of the toenails. Clinically, a diagnosis of onychomycosis was made. Potassium hydroxide examination of a scraping from the subungual region showed fungal elements. Trichophyton rubrum on Sabouraud dextrose agar was determined.

Figure 1. Onycholysis and onychodystrophy affecting the toes.

Figure 2. In vivo confocal image of hyphae (arrows).

We performed both in vivo and in vitro confocal laser scanning microscopic examination of the nail of the right great toe (Figure 2). For the diagnosis of onychomycosis in our case, we used a multilaser reflectance confocal microscope (RCM) with a wavelength of 786 nm. In vivo confocal microscopy of the nail revealed branching hyphae just below the surface of the nail plate. Hyphae were seen as refractile, bright, linear structures along the laminates of the nail.

Onychomycosis is a common condition affecting 5.5% of the population worldwide and representing 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.1,2 There are many methods available to confirm the clinical diagnosis of onychomycosis by detecting the causative organisms. Direct microscopic examination of the scraping with a KOH culture, histopathologic assessment with periodic acid–Schiff staining, immunofluorescence analysis with calcofluor white staining, enzyme analysis, and polymerase chain reaction can be used for diagnosis of fungal infections. The most frequently used diagnostic method for onychomycosis is KOH examination of the scraping; however, fungal culture and histopathologic examination also can be used in cases having diagnostic difficulties.1,3,4 There are many studies comparing the efficacies of these methods in the literature.5-9

The causative fungal agent should be determined with at least 1 laboratory method due to the high cost, long duration, and serious potential adverse effects of systemic antifungal treatment. Direct microscopic examination with KOH in the diagnosis of onychomycosis is simple, fast, and inexpensive. However, inadequate material, using crystallized KOH for hydrolysis, insufficient or too much hydrolysis of scrapings, inappropriate staining, and not scanning all areas in the microscopy produce false-negative results. Similarly, secondary contamination of hair, cotton, yarn, or air bubbles mimicking fungal structures can cause false-positive results.9,10

Fungal culture is another diagnostic method that is accepted as the gold standard for diagnosis of onychomycosis.9 However, fungal cultures were positive in only 43% to 50% of all cases of onychomycosis that were diagnosed with other methods,11,12 which may be due to the loss of viability and ability of the fungi to grow in culture media during the transport. A major advantage of fungal culture is that the fungal agent can be classified as dermatophyte, nondermatophyte, mold, or yeast. However, culture does determine if the growing fungi is contamination or the real pathogen. Moreover, it is necessary to wait 3 to 4 weeks for culture results. For nondermatophyte fungi this time may be much longer.12

In vivo RCM is a noninvasive imaging method that allows optical en face sectioning of the living tissue with high resolution. Currently, RCM has a wide range of applications, such as the evaluation of both benign and malignant skin lesions in clinical dermatology.13

In vivo RCM was used first by Hongcharu et al.14 The diagnoses of onychomycosis and fungal hyphae were shown both in vivo and in vitro.14 The sensitivity and specificity of confocal examination in the diagnosis of onychomycosis is not known yet. Large clinical trials are needed to assess the sensitivity and specificity of this method in diagnosing fungal infections.

Onychomycosis is a contagious infectious disease characterized by hyphae proliferation in the nail plate. Definitive diagnosis is necessary before treatment because onychomycosis can be mistaken for many infectious or noninfectious skin diseases with nail involvement. Conventional methods are time consuming, laborious, and less reliable. Instead of high-cost procedures, in vivo confocal microscopic examination can be a rapid and reliable diagnostic method for onychomycosis in the near future.

References

1. Singal A, Khanna D. Onychomycosis: diagnosis and management. Indian J Dermatol Venereol Leprol. 2011;77:659-672.

2. Kaur R, Kashyap B, Bhalla P. Onychomycosis—epidemiology, diagnosis and management. Indian J Med Microbiol. 2008;26:108-116.

3. Richardson MD. Diagnosis and pathogenesis of dermatophyte infections. Br J Clin Pract Suppl. 1990;71:98-102.

4. Jensen RH, Arendrup MC. Molecular diagnosis of dermato-phyte infections. Curr Opin Infect Dis. 2012;25:126-134.

5. Weinberg JM, Koestenblatt EK, Tutrone WD, et al. Comparison of diagnostic methods in the evaluation of onychomycosis. J Am Acad Dermatol. 2003;49:193-197.

6. Gianni C, Morelli V, Cerri A, et al. Usefulness of histological examination for the diagnosis of onychomycosis. Dermatology. 2001;202:283-288.

7. Machler BC, Kirsner RS, Elgart GW. Routine histologic examination for the diagnosis of onychomycosis: an evaluation of sensitivity and specificity. Cutis. 1998;61:217-219.

8. Wilsmann-Theis D, Sareika F, Bieber T, et al. New reasons for histopathological nail-clipping examination in the diagnosis of onychomycosis. J Eur Acad Dermatol Venereol. 2011;25:235-237.

9. Reisberger EM, Abels C, Landthaler M, et al. Histopathological diagnosis of onychomycosis by periodic acid-Schiff-stained nail clippings. Br J Dermatol. 2003;148:749-754.

10. Shemer A, Trau H, Davidovici B, et al. Collection of fungi samples from nails: comparative study of curettage and drilling techniques. J Eur Acad Dermatol Venereol. 2008;22:182-185.

11. Daniel CR 3rd, Elewski BE. The diagnosis of nail fungus infection revisited. Arch Dermatol. 2000;136:1162-1164.

12. Borkowski P, Williams M, Holewinski J, et al. Onychomycosis: an analysis of 50 cases and a comparison of diagnostic techniques. J Am Podiatr Med Assoc. 2001;91:351-355.

13. Rajadhyaksha M, Gonzalez S, Zavislan JM, et al. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol. 1999;113:293-303.

14. Hongcharu W, Dwyer P, Gonzalez S, et al. Confirmation of onychomycosis by in vivo confocal microscopy. J Am Acad Dermatol. 2000;42(2, pt 1):214-216.

References

1. Singal A, Khanna D. Onychomycosis: diagnosis and management. Indian J Dermatol Venereol Leprol. 2011;77:659-672.

2. Kaur R, Kashyap B, Bhalla P. Onychomycosis—epidemiology, diagnosis and management. Indian J Med Microbiol. 2008;26:108-116.

3. Richardson MD. Diagnosis and pathogenesis of dermatophyte infections. Br J Clin Pract Suppl. 1990;71:98-102.

4. Jensen RH, Arendrup MC. Molecular diagnosis of dermato-phyte infections. Curr Opin Infect Dis. 2012;25:126-134.

5. Weinberg JM, Koestenblatt EK, Tutrone WD, et al. Comparison of diagnostic methods in the evaluation of onychomycosis. J Am Acad Dermatol. 2003;49:193-197.

6. Gianni C, Morelli V, Cerri A, et al. Usefulness of histological examination for the diagnosis of onychomycosis. Dermatology. 2001;202:283-288.

7. Machler BC, Kirsner RS, Elgart GW. Routine histologic examination for the diagnosis of onychomycosis: an evaluation of sensitivity and specificity. Cutis. 1998;61:217-219.

8. Wilsmann-Theis D, Sareika F, Bieber T, et al. New reasons for histopathological nail-clipping examination in the diagnosis of onychomycosis. J Eur Acad Dermatol Venereol. 2011;25:235-237.

9. Reisberger EM, Abels C, Landthaler M, et al. Histopathological diagnosis of onychomycosis by periodic acid-Schiff-stained nail clippings. Br J Dermatol. 2003;148:749-754.

10. Shemer A, Trau H, Davidovici B, et al. Collection of fungi samples from nails: comparative study of curettage and drilling techniques. J Eur Acad Dermatol Venereol. 2008;22:182-185.

11. Daniel CR 3rd, Elewski BE. The diagnosis of nail fungus infection revisited. Arch Dermatol. 2000;136:1162-1164.

12. Borkowski P, Williams M, Holewinski J, et al. Onychomycosis: an analysis of 50 cases and a comparison of diagnostic techniques. J Am Podiatr Med Assoc. 2001;91:351-355.

13. Rajadhyaksha M, Gonzalez S, Zavislan JM, et al. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol. 1999;113:293-303.

14. Hongcharu W, Dwyer P, Gonzalez S, et al. Confirmation of onychomycosis by in vivo confocal microscopy. J Am Acad Dermatol. 2000;42(2, pt 1):214-216.

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Cutis - 95(4)
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Cutis - 95(4)
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In Vivo Confocal Microscopy in the Diagnosis of Onychomycosis
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onychomycosis, confocal microscopy, diagnotic methods
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