Focus Dermatopathology – Case for Diagnosis DOI: 10.1111/ddg.12429
Rapidly evolving painful ulcerated plaque on the hand
Pedro Mendes-Bastos, Cristina Amaro, Fernando Assis-Pacheco, Jorge Cardoso Department of Dermatology and Venereology, Hospital de Curry Cabral–Centro Hospitalar de Lisboa Central, Lisboa, Portugal Dermatopathology Section – Quiz Case (Prof. Dr. D. Metze)
History An 85-year-old man was referred because of a painful skin lesion on his right hand which had been present for three weeks. His medical history was relevant for diabetic nephropathy on hemodialysis. On physical examination an erythematous well-defined plaque with a violaceous border and pustular surface was observed on the central dorsal aspect of the right hand (Figure 1a). One
week later, worsening was obvious, with foci of ulceration (Figure 1b). A punch biopsy was performed and histopathological examination revealed an intense neutrophilic infiltrate in the superficial and deep dermis, foci of epidermal neutrophilic exocytosis and some endothelial swelling without vasculitis (Figure 2a–c). Grocott, Ziehl-Neelsen and PAS stains were all negative. Blood test results revealed an elevated erythrocyte sedimentation rate (64 mm/h), with normal white blood cell count.
Figure 1 An erythematous well-defined plaque with a violaceous border and pustular surface on the dorsal aspect of the right hand, had developed over three weeks (a); Progression of the lesion, one week after the first clinical observation (b); full recovery after only one week of systemic prednisolone (c).
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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Focus Dermatopathology – Case for Diagnosis
Figure 2 At low magnification, dermal edema and a dense inflammatory infiltrate in the papillary and reticular dermis were observed (haematoxylin and eosin, original magnification × 10) (a). At higher magnification a neutrophilic inflammatory infiltrate fills the dermis, with discrete focal neutrophil exocytosis (haematoxylin and eosin, original magnification × 100) (b). Noticeable endothelial swelling with neutrophils tightly arranged around the vessels; however, overt leukocytoclasia, true vasculitis or fibrinoid necrosis were absent (haematoxylin and eosin, original magnification × 100) (c).
Your diagnosis?
1144
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Focus Dermatopathology – Case for Diagnosis Diagnosis: Neutrophilic dermatosis of the hands
Discussion The patient was treated with oral prednisolone 0.5 mg/Kg/ day and local potassium permanganate wet soaks (1 : 20 000) with full recovery after one week of treatment (Figure 1c). Herpes simplex PCR and bacterial, fungal and mycobacterial cultures were negative. Imaging and endoscopic studies were unremarkable. At 6-month follow-up, the condition recurred but was easily controlled with topical c lobetasol propionate cream. Neutrophilic dermatosis of the hands (NDH) is a rare, recently described inflammatory skin disease, included in the group of neutrophilic dermatoses. It mainly occurs in women (69 % of cases) [1] in the 7th decade of life [2] and it is clinically characterized by papules, plaques, pustules, bullae or ulcers usually limited to one or both hands, though other skin areas can be affected [1–3]. The lesions usually heal without scarring [4]. Like other neutrophilic dermatoses, systemic symptoms or signs such as fever, malaise, a rthralgias or lymphadenopathy, can accompany the skin lesions. In onethird of patients, blood tests may show elevated sedimentation rate, high C-reactive protein, leukocytosis or neutrophilia [1, 3]. Clinical and histopathological knowledge on this entity has been constantly evolving through the last two decades. First described by Strutton et al. in 1995 as “pustular vasculitis of the dorsal hands”, leukocytoclastic vasculitis was initially thought to be a constant histologic finding [4]. Then in 2000, Galaria et al. reported patients with similar clinical and histologic findings, but lacking true vasculitis [5]. Much discussion regarding the defining histopathology aspects arose in the following years. In 2002 Malone et al. admitted that vascular damage was probably secondary to the inflammation and not the primary pathophysiological event [6]; Gilaberte et al. speculated that biopsies performed earlier in the disease course would not have vasculitis and that lesions biopsied later on (like in Strutton’s patients) were more likely to show vasculitis, secondary to the persistent neutrophilic inflammation [7]. Direct immunofluorescence studies on lesional skin have been negative for immunoglobulins or complement [8]. In 2002 Cohen reaffirmed previous opinions and classified the entity “neutrophilic dermatosis of the dorsal hands” as a localized variant of Sweet syndrome and definitely not a vasculitis [8]. A growing number of reported cases with involvement of both, the dorsal and palmar surfaces as well as the fingers and lateral border of the hand lead to the accepted current designation: NDH.
Differential diagnostic considerations include infections, pustular drug reactions, erosive pustular dermatosis, erythema elevatum et diutinum, Sweet syndrome and atypical pyoderma gangrenosum. Due to clinical and histopathological overlap, NDH, Sweet syndrome and atypical pyoderma gangrenosum are probably a disease continuum in the spectrum of the neutrophilic dermatoses. A variety of diseases including malignancies, inflammatory bowel disease or infection have been described in patients with NDH but the nature of this association is not yet clear [9]. The absence of specific findings to differentiate the neutrophilic dermatoses may sometimes render an exact diagnosis impossible. In that case, clinicians should focus on the individual context of each patient in order to define the most appropriate clinical assessment and treatment. In conclusion, it is generally accepted today that the t ypical histopathological findings of neutrophilic dermatosis of the hands include a neutrophilic inflammatory infiltrate in the papillary and reticular dermis and occasionally intraepidermal pustules, neutrophilic exocytosis, leukocytoclasia or overt secondary vasculitis. Direct immunofluorescence is assumed to be negative but further studies are necessary. Clinical-pathological correlation is key to the diagnosis. Conflict of interest None. Correspondence to Dr. Pedro Mendes-Bastos Department of Dermatology and Venereology Hospital de Curry Cabral R. Beneficiência 8 1069-166 Lisboa, Portugal E-mail: [email protected]
References 1
2
3
4 5
Walling HW, Snipes CJ, Gerami P, Piette W. The relationship between neutrophilic dermatosis of the dorsal hands and sweet syndrome. Arch Dermatol 2006; 142: 57–63. Brajon D, Cuny JF, Barbaud A, Schmutz JL. Dermatose neutrophilique des mains. Ann Dermatol Venereol 2011; 138: 673–6. Byun JW, Hong WK, Song HJ et al. A case of neutrophilic dermatosis of the hands with concomitant involvement of the lips. Ann Dermatol 2010; 22: 106–9. Strutton G, Weedon D, Robertson J. Pustular vasculitis of the dorsal hands. J Am Acad Dermatol 1995; 32: 192–8. Galaria NA, Junkins-Hopkins JM, Kligman D, James WD. Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited. J Am Acad Dermatol 2000; 43: 870–4.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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Focus Dermatopathology – Case for Diagnosis
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Malone JC, Stone SP, Wills-Frank LA et al. Vascular inflammation (vasculitis) in sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol 2002; 138: 345–9. Gilaberte Y, Coscojuela C, Garcia-Prats MD. Neutrophilic dermatosis of the dorsal hands versus pustular vasculitis. J Am Acad Dermatol 2002; 46: 962–3.
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Cohen PR. Skin lesions of sweet syndrome and its dorsal ariant contain vasculitis: an oxymoron or an epiphenomv enon? Arch Dermatol 2002; 138: 400–2. Wang YS, Tan A. Neutrophilic dermatosis of the dorsal hands: an emerging entity. J Eur Acad Dermatol Venereol 2009; 23(4): 451–2.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Rapidly evolving painful ulcerated plaque on the hand
Pedro Mendes-Bastos, Cristina Amaro, Fernando Assis-Pacheco, Jorge Cardoso Department of Dermatology and Venereology, Hospital de Curry Cabral–Centro Hospitalar de Lisboa Central, Lisboa, Portugal Dermatopathology Section – Quiz Case (Prof. Dr. D. Metze)
History An 85-year-old man was referred because of a painful skin lesion on his right hand which had been present for three weeks. His medical history was relevant for diabetic nephropathy on hemodialysis. On physical examination an erythematous well-defined plaque with a violaceous border and pustular surface was observed on the central dorsal aspect of the right hand (Figure 1a). One
week later, worsening was obvious, with foci of ulceration (Figure 1b). A punch biopsy was performed and histopathological examination revealed an intense neutrophilic infiltrate in the superficial and deep dermis, foci of epidermal neutrophilic exocytosis and some endothelial swelling without vasculitis (Figure 2a–c). Grocott, Ziehl-Neelsen and PAS stains were all negative. Blood test results revealed an elevated erythrocyte sedimentation rate (64 mm/h), with normal white blood cell count.
Figure 1 An erythematous well-defined plaque with a violaceous border and pustular surface on the dorsal aspect of the right hand, had developed over three weeks (a); Progression of the lesion, one week after the first clinical observation (b); full recovery after only one week of systemic prednisolone (c).
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
1143
Focus Dermatopathology – Case for Diagnosis
Figure 2 At low magnification, dermal edema and a dense inflammatory infiltrate in the papillary and reticular dermis were observed (haematoxylin and eosin, original magnification × 10) (a). At higher magnification a neutrophilic inflammatory infiltrate fills the dermis, with discrete focal neutrophil exocytosis (haematoxylin and eosin, original magnification × 100) (b). Noticeable endothelial swelling with neutrophils tightly arranged around the vessels; however, overt leukocytoclasia, true vasculitis or fibrinoid necrosis were absent (haematoxylin and eosin, original magnification × 100) (c).
Your diagnosis?
1144
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Focus Dermatopathology – Case for Diagnosis Diagnosis: Neutrophilic dermatosis of the hands
Discussion The patient was treated with oral prednisolone 0.5 mg/Kg/ day and local potassium permanganate wet soaks (1 : 20 000) with full recovery after one week of treatment (Figure 1c). Herpes simplex PCR and bacterial, fungal and mycobacterial cultures were negative. Imaging and endoscopic studies were unremarkable. At 6-month follow-up, the condition recurred but was easily controlled with topical c lobetasol propionate cream. Neutrophilic dermatosis of the hands (NDH) is a rare, recently described inflammatory skin disease, included in the group of neutrophilic dermatoses. It mainly occurs in women (69 % of cases) [1] in the 7th decade of life [2] and it is clinically characterized by papules, plaques, pustules, bullae or ulcers usually limited to one or both hands, though other skin areas can be affected [1–3]. The lesions usually heal without scarring [4]. Like other neutrophilic dermatoses, systemic symptoms or signs such as fever, malaise, a rthralgias or lymphadenopathy, can accompany the skin lesions. In onethird of patients, blood tests may show elevated sedimentation rate, high C-reactive protein, leukocytosis or neutrophilia [1, 3]. Clinical and histopathological knowledge on this entity has been constantly evolving through the last two decades. First described by Strutton et al. in 1995 as “pustular vasculitis of the dorsal hands”, leukocytoclastic vasculitis was initially thought to be a constant histologic finding [4]. Then in 2000, Galaria et al. reported patients with similar clinical and histologic findings, but lacking true vasculitis [5]. Much discussion regarding the defining histopathology aspects arose in the following years. In 2002 Malone et al. admitted that vascular damage was probably secondary to the inflammation and not the primary pathophysiological event [6]; Gilaberte et al. speculated that biopsies performed earlier in the disease course would not have vasculitis and that lesions biopsied later on (like in Strutton’s patients) were more likely to show vasculitis, secondary to the persistent neutrophilic inflammation [7]. Direct immunofluorescence studies on lesional skin have been negative for immunoglobulins or complement [8]. In 2002 Cohen reaffirmed previous opinions and classified the entity “neutrophilic dermatosis of the dorsal hands” as a localized variant of Sweet syndrome and definitely not a vasculitis [8]. A growing number of reported cases with involvement of both, the dorsal and palmar surfaces as well as the fingers and lateral border of the hand lead to the accepted current designation: NDH.
Differential diagnostic considerations include infections, pustular drug reactions, erosive pustular dermatosis, erythema elevatum et diutinum, Sweet syndrome and atypical pyoderma gangrenosum. Due to clinical and histopathological overlap, NDH, Sweet syndrome and atypical pyoderma gangrenosum are probably a disease continuum in the spectrum of the neutrophilic dermatoses. A variety of diseases including malignancies, inflammatory bowel disease or infection have been described in patients with NDH but the nature of this association is not yet clear [9]. The absence of specific findings to differentiate the neutrophilic dermatoses may sometimes render an exact diagnosis impossible. In that case, clinicians should focus on the individual context of each patient in order to define the most appropriate clinical assessment and treatment. In conclusion, it is generally accepted today that the t ypical histopathological findings of neutrophilic dermatosis of the hands include a neutrophilic inflammatory infiltrate in the papillary and reticular dermis and occasionally intraepidermal pustules, neutrophilic exocytosis, leukocytoclasia or overt secondary vasculitis. Direct immunofluorescence is assumed to be negative but further studies are necessary. Clinical-pathological correlation is key to the diagnosis. Conflict of interest None. Correspondence to Dr. Pedro Mendes-Bastos Department of Dermatology and Venereology Hospital de Curry Cabral R. Beneficiência 8 1069-166 Lisboa, Portugal E-mail: [email protected]
References 1
2
3
4 5
Walling HW, Snipes CJ, Gerami P, Piette W. The relationship between neutrophilic dermatosis of the dorsal hands and sweet syndrome. Arch Dermatol 2006; 142: 57–63. Brajon D, Cuny JF, Barbaud A, Schmutz JL. Dermatose neutrophilique des mains. Ann Dermatol Venereol 2011; 138: 673–6. Byun JW, Hong WK, Song HJ et al. A case of neutrophilic dermatosis of the hands with concomitant involvement of the lips. Ann Dermatol 2010; 22: 106–9. Strutton G, Weedon D, Robertson J. Pustular vasculitis of the dorsal hands. J Am Acad Dermatol 1995; 32: 192–8. Galaria NA, Junkins-Hopkins JM, Kligman D, James WD. Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited. J Am Acad Dermatol 2000; 43: 870–4.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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Focus Dermatopathology – Case for Diagnosis
6
7
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Malone JC, Stone SP, Wills-Frank LA et al. Vascular inflammation (vasculitis) in sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol 2002; 138: 345–9. Gilaberte Y, Coscojuela C, Garcia-Prats MD. Neutrophilic dermatosis of the dorsal hands versus pustular vasculitis. J Am Acad Dermatol 2002; 46: 962–3.
8
9
Cohen PR. Skin lesions of sweet syndrome and its dorsal ariant contain vasculitis: an oxymoron or an epiphenomv enon? Arch Dermatol 2002; 138: 400–2. Wang YS, Tan A. Neutrophilic dermatosis of the dorsal hands: an emerging entity. J Eur Acad Dermatol Venereol 2009; 23(4): 451–2.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
