Letters to the Editor
383
Table 1 Summary of nine cases with herpes zoster diagnosis in anamnesis Patient
Age
Duration of psoriasis (years)
Age of HZ diagnosis
Treatment at the time of HZ diagnosis
1
52
34
40
Topical CS
2
74
42
Unknown
Unknown
3
62
15
25
No TP (before psoriasis)
4
76
10
76
Topical CS
5
73
43
67
CyA
6
67
24
60
CyA
7
78
10
74
Phototherapy
8
60
40
Unknown
Unknown
9
60
22
54
Topical CS
HZ, herpes zoster; CyA, cyclosporine A; TP, therapy; CS, corticosteroids
and nail psoriasis (2), for at least 3 years (range 3–65 years), on various therapeutic regimens. Thirty-five per cent of our patients had been treated with systemic biological treatment, 22% with PUVA/UVB phototherapy, 9% with traditional drugs (CyA, methotrexate) and 32% topically. In two patients (2%), no treatment was administered. The mean age was 54.4 years (range 29– 78 years). None had a history of PR. Nine patients (9%) reported a history of HZ. In six cases, HZ developed during the psoriasis course and in one case (1%) HZ occurred before the psoriasis onset. In two cases, the time of HZ diagnosis remained unknown (Table 1), so they were not included in the analysis of the prevalence in our study. As regards the type of treatment administered to six patients who had an episode of HZ during the course of psoriasis, we obtained the following data: two patients developed HZ during the treatment with CyA, one patient during phototherapy and three patients during a topical treatment. Although biologics were mostly administered to our patients with psoriasis (35%), no viral reactivation was recorded in this group. Contrarily to PR, which was not recorded at all, the prevalence of HZ (6%) in psoriatic patients was higher than expected, given its incidence among the general population (1.5–3.5 per 1000).2 This may be due to the different impact the two diseases may have on the recollection of the patient. Being painful, HZ may be recalled more easily than the almost asymptomatic PR. Alternatively, the different prevalence of reactivation of PR and HZ suggests that different mechanisms of reactivation of HHVs, namely, systemic in PR and peripheral in HZ, may be at work in psoriasis. S. Javor,* F. Drago, A. Rebora, E. Cozzani, A. Parodi DISSAL, Section of Dermatology, IRCCS A.O.U. San Martino-IST Genoa, Genoa, Italy *Correspondence: S. Javor. E-mail: [email protected]
References 1 Adelzadeh L, Jourabchi N, Wu JJ. The risk of herpes zoster during biological therapy for psoriasis and other inflammatory conditions. J Eur Acad Dermatol Venereol 2014; 28: 846–852.
JEADV 2016, 30, 320–386
2 Gnann JW, Jr, Whitley RJ. Clinical practice: herpes zoster. New Engl J Med 2002; 347: 340–346. 3 Chuh A, Lee A, Zawar V, Sciallis G, Kempf W. Pityriasis rosea–an update. Indian J Dermatol Venereol Leprol 2005; 71: 311–315. 4 Broccolo F, Drago F, Careddu AM et al. Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005; 124: 1234–1240. 5 Dreiher J, Kresch FS, Comaneshter D, Cohen AD. Risk of Herpes zoster in patients with psoriasis treated with biologic drugs. J Eur Acad Dermatol Venereol 2012; 26: 1127–1132. DOI: 10.1111/jdv.12816
Clearance of atypical facial necrobiosis lipoidica with tacrolimus ointment Editor Necrobiosis lipoidica is a disease of unknown cause closely associated with diabetes mellitus.1,2 Lesions are present at sites other than the legs, particularly on the hands, fingers, forearms, face and scalp in about 15% of necrobiosis lipoidica patients.1,2 Furthermore, necrobiosis lipoidica with lesions exclusively outside the legs occurs in fewer than 2% of patients. Clinical correct diagnosis may be difficult because of the atypical location and atypical appearance in these cases. These cases have been termed ‘atypical facial necrobiosis lipoidica’.3–5 Here, we describe the case of atypical facial necrobiosis lipoidica effectively treated with tacrolimus, 0.1%, ointment. A 45-year-old woman presented with a 1-year history of asymptomatic firm triangular infiltrated plaque on the right cheek. The lesion had enlarged peripherally, was erythematous and had irregular borders with pityriasis. The centre showed a slightly waxy appearance (Fig. 1a). Laboratory investigation revealed elevated HbA1c of 11.4% (normal range, 4.6–6.2%).
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
384
(a)
(b)
Figure 1 (a) Clinical features of the lesion. Erythematous triangular plaque with raised borders accompanying pityriasis. (b) Examination at 1 year-follow-up showed long-term clearance of lesions after treatment with tacrolimus ointment.
Her blood results were: glucose, 334 mg/dL (normal range 70– 100 mg/dL); uric acid, 6.1 mg/dL (normal range 2.7–5.8 mg/ dL). Serum angiotensin converting enzyme and lysozyme levels were within normal limits. Radiologic studies including chest X ray, computed tomography and systemic scintigraphy using 67 Ga-citrate did not demonstrate any abnormalities. Ophthalmologic examination showed no evidence of sarcoidosis. Oral glucose tolerance test revealed that she had diabetes mellitus type 2. Fungal culture of skin biopsy specimens was also negative. Histological examination revealed that the epidermis is slightly atrophic (Fig. 2a). The degenerative collagen fibres were
(a)
(c)
(b)
(d)
JEADV 2016, 30, 320–386
surrounded with palisades of infiltrated cells (Fig. 2b,c). There were granulomatous infiltrates with conspicuous multinucleate giant cells (Fig. 2b). These giant cells were not Touton giant cells. Elastica van Gieson staining revealed that there were many conspicuous giant cells. Phagocytosis of elastic fibres by multinucleated giant cells was not observed (Fig. 2d). There were no fungi, mycobacteria or foreign body demonstrated by periodic acid–Schiff stain and Elastica van Gieson stain. Based on these clinical and histological results, a diagnosis of atypical facial necrobiosis lipoidica was made. Referral to a diabetes specialist was immediately conducted to treat the patient’s diabetes mellitus
Figure 2 (a) Histological examination revealed that the epidermis is slightly atrophic. (b) The degenerative collagen fibres were surrounded with palisades of infiltrated cells. There were granulomatous infiltrates with conspicuous multinucleate giant cells. (c) Necrobiosis was present. Note the complete absence of elastic fibres. (d) Elastica van Gieson staining revealed that there were many conspicuous giant cells. Phagocytosis of elastic fibres by multinucleated giant cells was not observed (H&E: a 9 1; b 9 40; c 9 100; Elastica van Gieson: d 9 100).
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
type 2. Her diabetes has been controlled with metformin, sitagliptin and insulin lispro (fast acting insulin analogue). Her skin lesion has been treated with topical tacrolimus 0.1% ointment. With tacrolimus, the skin lesion improved quickly and showed marked improvement after 1 year (Fig. 1b). The reason why we diagnosed this case as atypical facial necrobiosis lipoidica is as follows. Firstly, the lesion was single. Secondly, the lesion arouse on the patient’s face. Thirdly, histological analysis revealed that necrobiosis with giant cells existed in the lesional dermis. Fourthly, we could exclude the diagnosis of annular elastolytic giant cell granuloma because giant cells did not phagocytize elastic fibres. Fifthly, our patient did not have sarcoidosis of internal organs. Sixthly, the fungal infection was denied because fungal culture of skin biopsy specimens was negative. No fungus was detected with periodic acidSchiff stain. No one effective treatment has been established for atypical facial necrobiosis lipoidica.3–5 Many case reports have described the use of various treatments such as corticosteroids, infliximab, tretinoin, aspirin, dipyridamole, prostaglandin E1, clofazimine and cyclosporine. However, large randomized placebo-controlled trials are lacking.1,2 There are several reports describing the efficacy of tacrolimus ointment for necrobiosis lipoidica.6–9 Calcineurin inhibition might result in downregulation of T-cell activity and disturbance of cytokine transcription. It is intriguing to speculate that the therapeutic effect of tacrolimus may be effective through unrecognized effects on the function of the innate immune system. Further accumulation of cases will clarify the pathophysiology of this rare disease and advance the effective therapeutics.
Acknowledgements We thank T. Moriue and J. Moriue for intellectual discussions. This work was supported by grants from the Ministries of Health, Labour, and Welfare and Education, Culture, Sports, Science and Technology of Japan. A. Koura-Nishiura,1,† K. Yoneda,1,*,† K. Nakai,1 T. Demitsu,2 Y. Kubota1 1 Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, 2Department of Dermatology, Jichi Medical University, Saitama Medical Centre, Saitama, Japan *Correspondence: K. Yoneda. E-mail: [email protected] † These authors contributed equally to this work.
References 1 Cunliffe WJ. Necrobiotic disorders. In Champion RH, Burton JL, Burns PA, Breathnach SM, eds. Textbook of Dermatology, Vol. 2, 6th edn. Blackwell Science, Oxford, UK, 1998: 2297–2309. 2 Reid SD, Ladizinski B, Lee K, Baibergenova A, Alavi A. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol 2013; 69: 783–791. 3 Forman L. Necrobiosis lipoidica diabeticorum of the sculp. Proc R Soc Med 1954; 47: 658.
JEADV 2016, 30, 320–386
385
4 Dowling GB, Jones EW. Atypical (annular) necrobiosis lipoidica of the face and scalp. A report of the clinical and histological features of 7 cases. Dermatologica 1967; 135: 11–26. 5 Jones EW. Necrobiosis lipoidica presenting on the face and scalp. An account of 29 patients and a detailed consideration of recent histochemical findings. Trans St Johns Hosp Dermatol Soc 1971; 57: 202–220. 6 Harth W, Linse R. Topical tacrolimus in granuloma annulare and necrobiosis lipoidica. Br J Dermatol 2004; 150: 792–794. 7 Clayton TH, Harrison PV. Successful treatment of chronic ulcerated necrobiosis lipoidica with 0.1% topical tacrolimus ointment. Br J Dermatol 2005; 152: 581–582. 8 Barth D, Harth W, Treudler R, Simon JC. Topical tacrolimus in necrobiosis lipoidica. Hautarzt 2011; 62: 459–462. 9 Patsatsi S, Kyriakou A, Sotiriadis D. Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus. Case Rep Dermatol 2011; 3: 89–93. DOI: 10.1111/jdv.12818
Isotretinoin-induced transverse leuconychia Editor Isotretinoin is a synthetic retinoid mainly used for the treatment of acne. Like all retinoids, isotretinoin has generally predictable mainly mucocutaneous adverse events.1 Retinoids can also cause nail changes. Reported nail changes induced by etretinate and acitretin include nail thinning, splitting, softening, fragility, Beau’s lines, onychomadesis, proximal onychoschizia (lamellar nail splitting), onycholysis, progressive onychoatrophy, subungual haemorrhage, elkonyxis, ‘curly nails’, chronic paronychia and pyogenic granulomas,. Isotretinoin has been reported to cause nail changes such as elkonyxis, nail fragility, onycholysis and median nail dystrophy.2–4 We report a patient with isotretinoin-induced transverse leuconychia. A 20-year-old, otherwise healthy man presented to our outpatient clinic suffering from severe cystic acne. He was commenced on isotretinoin 0.5 mg/kg (40 mg) daily, after physical examination and laboratory investigations. The treatment was highly effective and well tolerated with no major adverse effects reported. This dose was maintained. One month later he mentioned nail changes in the nails of all fingers. The examination showed white transverse lines running parallel to the lunula across the middle of almost all fingernails. The toenails were not affected. There were no palpable ridges and the lines persisted with blanching of the fingernails. Physical examination revealed no signs of systemic or other skin disease. Biochemistry routine tests revealed normal liver and renal function. The patient was not receiving any other medication save topical emollients for the xerosis caused by isotretinoin. Isotretinoin-induced transverse leuconychia was diagnosed. The patient agreed to continue isotretinoin therapy. Treatment was completed with the maximum dosage of 150 mg/kg. The transverse
© 2014 European Academy of Dermatology and Venereology
383
Table 1 Summary of nine cases with herpes zoster diagnosis in anamnesis Patient
Age
Duration of psoriasis (years)
Age of HZ diagnosis
Treatment at the time of HZ diagnosis
1
52
34
40
Topical CS
2
74
42
Unknown
Unknown
3
62
15
25
No TP (before psoriasis)
4
76
10
76
Topical CS
5
73
43
67
CyA
6
67
24
60
CyA
7
78
10
74
Phototherapy
8
60
40
Unknown
Unknown
9
60
22
54
Topical CS
HZ, herpes zoster; CyA, cyclosporine A; TP, therapy; CS, corticosteroids
and nail psoriasis (2), for at least 3 years (range 3–65 years), on various therapeutic regimens. Thirty-five per cent of our patients had been treated with systemic biological treatment, 22% with PUVA/UVB phototherapy, 9% with traditional drugs (CyA, methotrexate) and 32% topically. In two patients (2%), no treatment was administered. The mean age was 54.4 years (range 29– 78 years). None had a history of PR. Nine patients (9%) reported a history of HZ. In six cases, HZ developed during the psoriasis course and in one case (1%) HZ occurred before the psoriasis onset. In two cases, the time of HZ diagnosis remained unknown (Table 1), so they were not included in the analysis of the prevalence in our study. As regards the type of treatment administered to six patients who had an episode of HZ during the course of psoriasis, we obtained the following data: two patients developed HZ during the treatment with CyA, one patient during phototherapy and three patients during a topical treatment. Although biologics were mostly administered to our patients with psoriasis (35%), no viral reactivation was recorded in this group. Contrarily to PR, which was not recorded at all, the prevalence of HZ (6%) in psoriatic patients was higher than expected, given its incidence among the general population (1.5–3.5 per 1000).2 This may be due to the different impact the two diseases may have on the recollection of the patient. Being painful, HZ may be recalled more easily than the almost asymptomatic PR. Alternatively, the different prevalence of reactivation of PR and HZ suggests that different mechanisms of reactivation of HHVs, namely, systemic in PR and peripheral in HZ, may be at work in psoriasis. S. Javor,* F. Drago, A. Rebora, E. Cozzani, A. Parodi DISSAL, Section of Dermatology, IRCCS A.O.U. San Martino-IST Genoa, Genoa, Italy *Correspondence: S. Javor. E-mail: [email protected]
References 1 Adelzadeh L, Jourabchi N, Wu JJ. The risk of herpes zoster during biological therapy for psoriasis and other inflammatory conditions. J Eur Acad Dermatol Venereol 2014; 28: 846–852.
JEADV 2016, 30, 320–386
2 Gnann JW, Jr, Whitley RJ. Clinical practice: herpes zoster. New Engl J Med 2002; 347: 340–346. 3 Chuh A, Lee A, Zawar V, Sciallis G, Kempf W. Pityriasis rosea–an update. Indian J Dermatol Venereol Leprol 2005; 71: 311–315. 4 Broccolo F, Drago F, Careddu AM et al. Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005; 124: 1234–1240. 5 Dreiher J, Kresch FS, Comaneshter D, Cohen AD. Risk of Herpes zoster in patients with psoriasis treated with biologic drugs. J Eur Acad Dermatol Venereol 2012; 26: 1127–1132. DOI: 10.1111/jdv.12816
Clearance of atypical facial necrobiosis lipoidica with tacrolimus ointment Editor Necrobiosis lipoidica is a disease of unknown cause closely associated with diabetes mellitus.1,2 Lesions are present at sites other than the legs, particularly on the hands, fingers, forearms, face and scalp in about 15% of necrobiosis lipoidica patients.1,2 Furthermore, necrobiosis lipoidica with lesions exclusively outside the legs occurs in fewer than 2% of patients. Clinical correct diagnosis may be difficult because of the atypical location and atypical appearance in these cases. These cases have been termed ‘atypical facial necrobiosis lipoidica’.3–5 Here, we describe the case of atypical facial necrobiosis lipoidica effectively treated with tacrolimus, 0.1%, ointment. A 45-year-old woman presented with a 1-year history of asymptomatic firm triangular infiltrated plaque on the right cheek. The lesion had enlarged peripherally, was erythematous and had irregular borders with pityriasis. The centre showed a slightly waxy appearance (Fig. 1a). Laboratory investigation revealed elevated HbA1c of 11.4% (normal range, 4.6–6.2%).
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
384
(a)
(b)
Figure 1 (a) Clinical features of the lesion. Erythematous triangular plaque with raised borders accompanying pityriasis. (b) Examination at 1 year-follow-up showed long-term clearance of lesions after treatment with tacrolimus ointment.
Her blood results were: glucose, 334 mg/dL (normal range 70– 100 mg/dL); uric acid, 6.1 mg/dL (normal range 2.7–5.8 mg/ dL). Serum angiotensin converting enzyme and lysozyme levels were within normal limits. Radiologic studies including chest X ray, computed tomography and systemic scintigraphy using 67 Ga-citrate did not demonstrate any abnormalities. Ophthalmologic examination showed no evidence of sarcoidosis. Oral glucose tolerance test revealed that she had diabetes mellitus type 2. Fungal culture of skin biopsy specimens was also negative. Histological examination revealed that the epidermis is slightly atrophic (Fig. 2a). The degenerative collagen fibres were
(a)
(c)
(b)
(d)
JEADV 2016, 30, 320–386
surrounded with palisades of infiltrated cells (Fig. 2b,c). There were granulomatous infiltrates with conspicuous multinucleate giant cells (Fig. 2b). These giant cells were not Touton giant cells. Elastica van Gieson staining revealed that there were many conspicuous giant cells. Phagocytosis of elastic fibres by multinucleated giant cells was not observed (Fig. 2d). There were no fungi, mycobacteria or foreign body demonstrated by periodic acid–Schiff stain and Elastica van Gieson stain. Based on these clinical and histological results, a diagnosis of atypical facial necrobiosis lipoidica was made. Referral to a diabetes specialist was immediately conducted to treat the patient’s diabetes mellitus
Figure 2 (a) Histological examination revealed that the epidermis is slightly atrophic. (b) The degenerative collagen fibres were surrounded with palisades of infiltrated cells. There were granulomatous infiltrates with conspicuous multinucleate giant cells. (c) Necrobiosis was present. Note the complete absence of elastic fibres. (d) Elastica van Gieson staining revealed that there were many conspicuous giant cells. Phagocytosis of elastic fibres by multinucleated giant cells was not observed (H&E: a 9 1; b 9 40; c 9 100; Elastica van Gieson: d 9 100).
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
type 2. Her diabetes has been controlled with metformin, sitagliptin and insulin lispro (fast acting insulin analogue). Her skin lesion has been treated with topical tacrolimus 0.1% ointment. With tacrolimus, the skin lesion improved quickly and showed marked improvement after 1 year (Fig. 1b). The reason why we diagnosed this case as atypical facial necrobiosis lipoidica is as follows. Firstly, the lesion was single. Secondly, the lesion arouse on the patient’s face. Thirdly, histological analysis revealed that necrobiosis with giant cells existed in the lesional dermis. Fourthly, we could exclude the diagnosis of annular elastolytic giant cell granuloma because giant cells did not phagocytize elastic fibres. Fifthly, our patient did not have sarcoidosis of internal organs. Sixthly, the fungal infection was denied because fungal culture of skin biopsy specimens was negative. No fungus was detected with periodic acidSchiff stain. No one effective treatment has been established for atypical facial necrobiosis lipoidica.3–5 Many case reports have described the use of various treatments such as corticosteroids, infliximab, tretinoin, aspirin, dipyridamole, prostaglandin E1, clofazimine and cyclosporine. However, large randomized placebo-controlled trials are lacking.1,2 There are several reports describing the efficacy of tacrolimus ointment for necrobiosis lipoidica.6–9 Calcineurin inhibition might result in downregulation of T-cell activity and disturbance of cytokine transcription. It is intriguing to speculate that the therapeutic effect of tacrolimus may be effective through unrecognized effects on the function of the innate immune system. Further accumulation of cases will clarify the pathophysiology of this rare disease and advance the effective therapeutics.
Acknowledgements We thank T. Moriue and J. Moriue for intellectual discussions. This work was supported by grants from the Ministries of Health, Labour, and Welfare and Education, Culture, Sports, Science and Technology of Japan. A. Koura-Nishiura,1,† K. Yoneda,1,*,† K. Nakai,1 T. Demitsu,2 Y. Kubota1 1 Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, 2Department of Dermatology, Jichi Medical University, Saitama Medical Centre, Saitama, Japan *Correspondence: K. Yoneda. E-mail: [email protected] † These authors contributed equally to this work.
References 1 Cunliffe WJ. Necrobiotic disorders. In Champion RH, Burton JL, Burns PA, Breathnach SM, eds. Textbook of Dermatology, Vol. 2, 6th edn. Blackwell Science, Oxford, UK, 1998: 2297–2309. 2 Reid SD, Ladizinski B, Lee K, Baibergenova A, Alavi A. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol 2013; 69: 783–791. 3 Forman L. Necrobiosis lipoidica diabeticorum of the sculp. Proc R Soc Med 1954; 47: 658.
JEADV 2016, 30, 320–386
385
4 Dowling GB, Jones EW. Atypical (annular) necrobiosis lipoidica of the face and scalp. A report of the clinical and histological features of 7 cases. Dermatologica 1967; 135: 11–26. 5 Jones EW. Necrobiosis lipoidica presenting on the face and scalp. An account of 29 patients and a detailed consideration of recent histochemical findings. Trans St Johns Hosp Dermatol Soc 1971; 57: 202–220. 6 Harth W, Linse R. Topical tacrolimus in granuloma annulare and necrobiosis lipoidica. Br J Dermatol 2004; 150: 792–794. 7 Clayton TH, Harrison PV. Successful treatment of chronic ulcerated necrobiosis lipoidica with 0.1% topical tacrolimus ointment. Br J Dermatol 2005; 152: 581–582. 8 Barth D, Harth W, Treudler R, Simon JC. Topical tacrolimus in necrobiosis lipoidica. Hautarzt 2011; 62: 459–462. 9 Patsatsi S, Kyriakou A, Sotiriadis D. Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus. Case Rep Dermatol 2011; 3: 89–93. DOI: 10.1111/jdv.12818
Isotretinoin-induced transverse leuconychia Editor Isotretinoin is a synthetic retinoid mainly used for the treatment of acne. Like all retinoids, isotretinoin has generally predictable mainly mucocutaneous adverse events.1 Retinoids can also cause nail changes. Reported nail changes induced by etretinate and acitretin include nail thinning, splitting, softening, fragility, Beau’s lines, onychomadesis, proximal onychoschizia (lamellar nail splitting), onycholysis, progressive onychoatrophy, subungual haemorrhage, elkonyxis, ‘curly nails’, chronic paronychia and pyogenic granulomas,. Isotretinoin has been reported to cause nail changes such as elkonyxis, nail fragility, onycholysis and median nail dystrophy.2–4 We report a patient with isotretinoin-induced transverse leuconychia. A 20-year-old, otherwise healthy man presented to our outpatient clinic suffering from severe cystic acne. He was commenced on isotretinoin 0.5 mg/kg (40 mg) daily, after physical examination and laboratory investigations. The treatment was highly effective and well tolerated with no major adverse effects reported. This dose was maintained. One month later he mentioned nail changes in the nails of all fingers. The examination showed white transverse lines running parallel to the lunula across the middle of almost all fingernails. The toenails were not affected. There were no palpable ridges and the lines persisted with blanching of the fingernails. Physical examination revealed no signs of systemic or other skin disease. Biochemistry routine tests revealed normal liver and renal function. The patient was not receiving any other medication save topical emollients for the xerosis caused by isotretinoin. Isotretinoin-induced transverse leuconychia was diagnosed. The patient agreed to continue isotretinoin therapy. Treatment was completed with the maximum dosage of 150 mg/kg. The transverse
© 2014 European Academy of Dermatology and Venereology
![[Necrobiosis lipoidica].](/assets/img/hold.png)
