CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Nail improvement during alitretinoin treatment: three case reports and review of the literature N. Milanesi, A. M. D’Erme and M. Gola Allergological and Occupational Dermatology Unit, Department of Surgery and Translational Medicine, University of Florence, Firenze, Italy doi:10.1111/ced.12584
Summary
Alitretinoin is an endogenous vitamin A derivative, 9-cis-retinoic acid. Its antiinflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid-responsive dermatoses associated with nail involvement.
Hand eczema is a common skin disorder, which is characterized by scaling, fissures, erythema, vesicles, papules, hyperkeratosis, pruritus and pain. There is little information about nail involvement in chronic hand eczema although irritant and allergic contact dermatitis, repeated working related trauma, frequent water exposure, abuse of corticosteroid drugs and long-term neglect can play a role in nail changes. Nail involvement often occurs in patients with psoriatic arthritis, psoriasis and isolated nail psoriasis, therefore acitretin has been reported to be effective in a few studies.1
Report We describe three patients followed in our centre, who had severe chronic hand eczema accompanied by nail dystrophy, who were treated with alitretinoin 30 mg daily for 6 months. We also briefly review the literature on this topic. Correspondence: Dr Nicola Milanesi, Allergological and Occupational Dermatology Unit, Department of Surgery and Translational Medicine, University of Florence, Viale Michelangelo, 41 50125 Firenze, Italy E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 14 August 2014
ª 2015 British Association of Dermatologists
Patient 1 was a 46-year-old atopic man, who presented with a 7-year history of severe palmar hyperkeratotic hand eczema. He reported a 1-year history of nail dystrophy. Previous treatment with topical and oral corticosteroids, phototherapy and topical calcineurin inhibitors brought no relief from the hand eczema. The patient worked as a scaffolder. On physical examination, median nail dystrophy was seen on both thumbnails, with characteristic fir-treeshaped fissures and Beau lines on the third and fourth fingers (Fig. 1a). Temporary relief from the cutaneous signs and symptoms was achieved by the use of oral ciclosporin, but the severity of the disease worsened markedly after treatment was stopped. Patch test readings were positive for para-phenylenediamine, but the reaction was not considered relevant. Patient 2 was a 62-year-old nonatopic man, who presented with a 6-year history of severe hand eczema and nail involvement affecting the first, second and third nails of both hands. On physical examination, the nails were found to have increased thickness and the nail plates were yellowish (Fig. 1b). Patch test readings were negative. The patient was a textile worker, who experienced prolonged mechanical trauma and repetitive exposure to water, alkali and solvents during his work activity.
Clinical and Experimental Dermatology
1
Nail improvement during alitretinoin treatment N. Milanesi et al.
(a)
(c)
(b)
(d)
Figure 1 (a–d) Onychodystrophy (a,c) before treatment and (b,d) after treatment with alitretinoin 30 mg.
Previous treatment courses, including emollients, topical and oral corticosteroids, oral antihistamines and acitretin had not led to a stable remission of the skin condition. A 40-year-old woman who had a history of atopic dermatitis since childhood presented with a 1-year history of exacerbation of skin lesions on both hands and all fingernails. She was a leather-craft worker. Physical examination revealed hand eczema, accompanied by paronychia, subungual hyperkeratosis, onychoschizia and onychodystrophy (Fig. 2a). The clinical condition did not respond to oral and potent topical corticosteroids. Patch test series were negative. None of the patients had a personal or family history of psoriasis, keratinization disorders or nail diseases. Tinea unguium and candidiasis were excluded by direct microscopy. Skin biopsy confirmed the diagnosis of eczema. No nail biopsies were taken. All patients confirmed that their work involved prolonged mechanical trauma and repetitive exposure to irritants such as water, alkali and solvents. Patients 1 and 2 also confirmed long-term neglect of the condition. None of the patients had previously received keratolytic ointment for the nail dystrophy. Patient 2 had received a previous treatment course with acitretin 25 mg daily but had minimal benefit after 4 months. There had been no reported improvement in his hands or nails, and he had asked for the drug to be discontinued. We diagnosed all the patients with severe chronic hand eczema accompanied by nail dystrophy, and started them on a 6-month course of systemic
2
Clinical and Experimental Dermatology
(a)
(b)
Figure 2 Improvement of lesions 4 months after the end of
therapy with alitretinoin.
alitretinoin 30 mg/day. All patients were educated about preventive and protective measures before, during and after alitretinoin treatment. No adverse events were recorded during treatment with alitretinoin. The clinical improvement was progressive. Almost
ª 2015 British Association of Dermatologists
Nail improvement during alitretinoin treatment N. Milanesi et al.
Table 1 Overview of patients treated with alitretinoin 30 mg.
Patient no.
Age, years
Sex
Duration of nail disease, years
1
46
M
1
2 3
62 40
M F
6 1
Symptoms Median nail dystrophy and Beau lines Onycogryphosis Onychodystrophy, paronychia and subungual hyperkeratosis
complete resolution of the nail dystrophy was observed at the end of therapy (Table 1; Fig. 1b,d), and 1 year later (7 months in patient 3), the result was stable and satisfactory(Fig. 2b). It has been suggested that hand eczema causes frequent periungual inflammation that can adversely affect proper functioning of the nail matrix, which in turn results in Beau lines or multiple depressive pits.2 There is some evidence in the literature of a clinical effect of retinoids on nail formation due to the presence of retinoid receptors on the nail matrix.3 Our positive results can be explained by the fact that alitretinoin binds both intracellular retinoid acid receptors (RAR and RXR), thus, compared with other retinoids, it has a stronger anti-inflammatory and immunomodulating effect by regulating keratinocyte proliferation and differentiation, cytokine production, leucocyte activity and antigen presentation.4 Alitretinoin is an endogenous retinoid, and acts as a panagonist. Its favourable safety and side effect profile makes it superior to acitretin, and it may provide an alternative for women who wish to consider pregnancy within 2 years. Our observation confirms that oral alitretinoin has considerable therapeutic potential as an oral immunomodulatory treatment in patients with chronic hand eczema, and it may also be effective in other retinoidresponsive dermatoses with nail involvement. We searched PubMed for studies reporting on nail dystrophy and alitretinoin treatment using the term ‘alitretinoin and nails’. Further articles were derived from other clinical reports. We found that to date, four cases have been reported. The first was a patient with 20-nail dystrophy, associated with lichen planus (LP), which was effectively treated with 6 months of treatment with alitretinoin 30 mg.3 The second patient had cutaneous, oral and oesophageal LP. All sites of LP improved after 6 months of alitretinoin 30 mg.5 A 15-year-old boy, who was affected by keratitis–ichthyosis–deafness (KID) with
ª 2015 British Association of Dermatologists
Treatment duration, months
Time to clinical improvement, months
Time to complete response, after treatment, months
6
5
4
6 6
4 1
2 4
dissecting cellulitis of the scalp and nail dystrophy affecting most of his fingers and all of his toes, was successfully treated with alitretinoin 10–20 mg/day for 5 months, and a significant improvement in all of his skin lesions was detectable.6 In addition, a case of median canaliform nail dystrophy has been documented as an adverse effect of alitretinoin treatment, which occurred after 16 months of alitretinoin 30 mg in a 53-year-old man with hand eczema.7 When treating patients with hand eczema, clinicians should also assess if they have nail disease, and consider management of this if present.2 A scoring system for quantifying nail involvement could be useful in patients with eczema to evaluate treatment outcomes. Our clinical observation is limited by a lack of a control group with isolated nail involvement. This would help to better differentiate the primary effect of alitretinoin on the nails from an improvement in nail changes secondary to that of hand eczema. The remarkable response to treatment in our three cases suggests that oral alitretinoin could play a role in suppressing disease activity and influencing nail formation. Nevertheless, lifestyle changes, skin care, preventive measures and short-term follow-up are recommended for all patients, and considered an integral part of the treatment. Continuous monitoring for adverse effects remains essential, and controlled clinical trials over extended periods of time are indicated.
Learning points ● Chronic hand eczema can be accompanied by
nail changes. ● Oral alitretinoin may be effective in retinoid-
responsive dermatoses with nail involvement.
Clinical and Experimental Dermatology
3
Nail improvement during alitretinoin treatment N. Milanesi et al.
References 1 Tosti A, Ricotti C, Romanelli P et al. Evaluation of the efficacy of acitretin therapy for nail psoriasis. Arch Dermatol 2009; 145: 269–71. 2 Yu M, Kim SW, Kim MS et al. Clinical study of patients with hand eczema accompanied by nail dystrophy. J Dermatol 2013; 40: 406–7. 3 Pinter A, P€atzold S, Kaufmann RJ. Lichen planus of nails successful treatment with alitretinoin. Dtsch Dermatol Ges 2011; 9: 1033–4. 4 Bissonnette R, Diepgen TL, Elsner P et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol 2010; 24(Suppl): 1–20.
4
Clinical and Experimental Dermatology
5 Kolios AG, Marques Maggio E, Gubler C et al. Oral, esophageal and cutaneous lichen ruber planus controlled with alitretinoin: case report and review of the literature. Dermatology 2013; 226: 302–10. 6 Prasad SC, Bygum A. Successful treatment with alitretinoin of dissecting cellulitis of the scalp in keratitisichthyosis-deafness syndrome. Acta Derm Venereol 2013; 93: 473–4. 7 Winther AH, Bygum A. Can median nail dystrophy be an adverse effect of alitretinoin treatment? Acta Derm Venereol 2014; 94: 719–20.
ª 2015 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Nail improvement during alitretinoin treatment: three case reports and review of the literature N. Milanesi, A. M. D’Erme and M. Gola Allergological and Occupational Dermatology Unit, Department of Surgery and Translational Medicine, University of Florence, Firenze, Italy doi:10.1111/ced.12584
Summary
Alitretinoin is an endogenous vitamin A derivative, 9-cis-retinoic acid. Its antiinflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid-responsive dermatoses associated with nail involvement.
Hand eczema is a common skin disorder, which is characterized by scaling, fissures, erythema, vesicles, papules, hyperkeratosis, pruritus and pain. There is little information about nail involvement in chronic hand eczema although irritant and allergic contact dermatitis, repeated working related trauma, frequent water exposure, abuse of corticosteroid drugs and long-term neglect can play a role in nail changes. Nail involvement often occurs in patients with psoriatic arthritis, psoriasis and isolated nail psoriasis, therefore acitretin has been reported to be effective in a few studies.1
Report We describe three patients followed in our centre, who had severe chronic hand eczema accompanied by nail dystrophy, who were treated with alitretinoin 30 mg daily for 6 months. We also briefly review the literature on this topic. Correspondence: Dr Nicola Milanesi, Allergological and Occupational Dermatology Unit, Department of Surgery and Translational Medicine, University of Florence, Viale Michelangelo, 41 50125 Firenze, Italy E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 14 August 2014
ª 2015 British Association of Dermatologists
Patient 1 was a 46-year-old atopic man, who presented with a 7-year history of severe palmar hyperkeratotic hand eczema. He reported a 1-year history of nail dystrophy. Previous treatment with topical and oral corticosteroids, phototherapy and topical calcineurin inhibitors brought no relief from the hand eczema. The patient worked as a scaffolder. On physical examination, median nail dystrophy was seen on both thumbnails, with characteristic fir-treeshaped fissures and Beau lines on the third and fourth fingers (Fig. 1a). Temporary relief from the cutaneous signs and symptoms was achieved by the use of oral ciclosporin, but the severity of the disease worsened markedly after treatment was stopped. Patch test readings were positive for para-phenylenediamine, but the reaction was not considered relevant. Patient 2 was a 62-year-old nonatopic man, who presented with a 6-year history of severe hand eczema and nail involvement affecting the first, second and third nails of both hands. On physical examination, the nails were found to have increased thickness and the nail plates were yellowish (Fig. 1b). Patch test readings were negative. The patient was a textile worker, who experienced prolonged mechanical trauma and repetitive exposure to water, alkali and solvents during his work activity.
Clinical and Experimental Dermatology
1
Nail improvement during alitretinoin treatment N. Milanesi et al.
(a)
(c)
(b)
(d)
Figure 1 (a–d) Onychodystrophy (a,c) before treatment and (b,d) after treatment with alitretinoin 30 mg.
Previous treatment courses, including emollients, topical and oral corticosteroids, oral antihistamines and acitretin had not led to a stable remission of the skin condition. A 40-year-old woman who had a history of atopic dermatitis since childhood presented with a 1-year history of exacerbation of skin lesions on both hands and all fingernails. She was a leather-craft worker. Physical examination revealed hand eczema, accompanied by paronychia, subungual hyperkeratosis, onychoschizia and onychodystrophy (Fig. 2a). The clinical condition did not respond to oral and potent topical corticosteroids. Patch test series were negative. None of the patients had a personal or family history of psoriasis, keratinization disorders or nail diseases. Tinea unguium and candidiasis were excluded by direct microscopy. Skin biopsy confirmed the diagnosis of eczema. No nail biopsies were taken. All patients confirmed that their work involved prolonged mechanical trauma and repetitive exposure to irritants such as water, alkali and solvents. Patients 1 and 2 also confirmed long-term neglect of the condition. None of the patients had previously received keratolytic ointment for the nail dystrophy. Patient 2 had received a previous treatment course with acitretin 25 mg daily but had minimal benefit after 4 months. There had been no reported improvement in his hands or nails, and he had asked for the drug to be discontinued. We diagnosed all the patients with severe chronic hand eczema accompanied by nail dystrophy, and started them on a 6-month course of systemic
2
Clinical and Experimental Dermatology
(a)
(b)
Figure 2 Improvement of lesions 4 months after the end of
therapy with alitretinoin.
alitretinoin 30 mg/day. All patients were educated about preventive and protective measures before, during and after alitretinoin treatment. No adverse events were recorded during treatment with alitretinoin. The clinical improvement was progressive. Almost
ª 2015 British Association of Dermatologists
Nail improvement during alitretinoin treatment N. Milanesi et al.
Table 1 Overview of patients treated with alitretinoin 30 mg.
Patient no.
Age, years
Sex
Duration of nail disease, years
1
46
M
1
2 3
62 40
M F
6 1
Symptoms Median nail dystrophy and Beau lines Onycogryphosis Onychodystrophy, paronychia and subungual hyperkeratosis
complete resolution of the nail dystrophy was observed at the end of therapy (Table 1; Fig. 1b,d), and 1 year later (7 months in patient 3), the result was stable and satisfactory(Fig. 2b). It has been suggested that hand eczema causes frequent periungual inflammation that can adversely affect proper functioning of the nail matrix, which in turn results in Beau lines or multiple depressive pits.2 There is some evidence in the literature of a clinical effect of retinoids on nail formation due to the presence of retinoid receptors on the nail matrix.3 Our positive results can be explained by the fact that alitretinoin binds both intracellular retinoid acid receptors (RAR and RXR), thus, compared with other retinoids, it has a stronger anti-inflammatory and immunomodulating effect by regulating keratinocyte proliferation and differentiation, cytokine production, leucocyte activity and antigen presentation.4 Alitretinoin is an endogenous retinoid, and acts as a panagonist. Its favourable safety and side effect profile makes it superior to acitretin, and it may provide an alternative for women who wish to consider pregnancy within 2 years. Our observation confirms that oral alitretinoin has considerable therapeutic potential as an oral immunomodulatory treatment in patients with chronic hand eczema, and it may also be effective in other retinoidresponsive dermatoses with nail involvement. We searched PubMed for studies reporting on nail dystrophy and alitretinoin treatment using the term ‘alitretinoin and nails’. Further articles were derived from other clinical reports. We found that to date, four cases have been reported. The first was a patient with 20-nail dystrophy, associated with lichen planus (LP), which was effectively treated with 6 months of treatment with alitretinoin 30 mg.3 The second patient had cutaneous, oral and oesophageal LP. All sites of LP improved after 6 months of alitretinoin 30 mg.5 A 15-year-old boy, who was affected by keratitis–ichthyosis–deafness (KID) with
ª 2015 British Association of Dermatologists
Treatment duration, months
Time to clinical improvement, months
Time to complete response, after treatment, months
6
5
4
6 6
4 1
2 4
dissecting cellulitis of the scalp and nail dystrophy affecting most of his fingers and all of his toes, was successfully treated with alitretinoin 10–20 mg/day for 5 months, and a significant improvement in all of his skin lesions was detectable.6 In addition, a case of median canaliform nail dystrophy has been documented as an adverse effect of alitretinoin treatment, which occurred after 16 months of alitretinoin 30 mg in a 53-year-old man with hand eczema.7 When treating patients with hand eczema, clinicians should also assess if they have nail disease, and consider management of this if present.2 A scoring system for quantifying nail involvement could be useful in patients with eczema to evaluate treatment outcomes. Our clinical observation is limited by a lack of a control group with isolated nail involvement. This would help to better differentiate the primary effect of alitretinoin on the nails from an improvement in nail changes secondary to that of hand eczema. The remarkable response to treatment in our three cases suggests that oral alitretinoin could play a role in suppressing disease activity and influencing nail formation. Nevertheless, lifestyle changes, skin care, preventive measures and short-term follow-up are recommended for all patients, and considered an integral part of the treatment. Continuous monitoring for adverse effects remains essential, and controlled clinical trials over extended periods of time are indicated.
Learning points ● Chronic hand eczema can be accompanied by
nail changes. ● Oral alitretinoin may be effective in retinoid-
responsive dermatoses with nail involvement.
Clinical and Experimental Dermatology
3
Nail improvement during alitretinoin treatment N. Milanesi et al.
References 1 Tosti A, Ricotti C, Romanelli P et al. Evaluation of the efficacy of acitretin therapy for nail psoriasis. Arch Dermatol 2009; 145: 269–71. 2 Yu M, Kim SW, Kim MS et al. Clinical study of patients with hand eczema accompanied by nail dystrophy. J Dermatol 2013; 40: 406–7. 3 Pinter A, P€atzold S, Kaufmann RJ. Lichen planus of nails successful treatment with alitretinoin. Dtsch Dermatol Ges 2011; 9: 1033–4. 4 Bissonnette R, Diepgen TL, Elsner P et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol 2010; 24(Suppl): 1–20.
4
Clinical and Experimental Dermatology
5 Kolios AG, Marques Maggio E, Gubler C et al. Oral, esophageal and cutaneous lichen ruber planus controlled with alitretinoin: case report and review of the literature. Dermatology 2013; 226: 302–10. 6 Prasad SC, Bygum A. Successful treatment with alitretinoin of dissecting cellulitis of the scalp in keratitisichthyosis-deafness syndrome. Acta Derm Venereol 2013; 93: 473–4. 7 Winther AH, Bygum A. Can median nail dystrophy be an adverse effect of alitretinoin treatment? Acta Derm Venereol 2014; 94: 719–20.
ª 2015 British Association of Dermatologists
