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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 3  |  Issue : 2  |  Page : 45-51

Histopathological aspects of neutrophilic dermatoses: Investigation of 38 cases and review of the literature


1 Department of Dermatology, Autoimmune Bullous Diseases Research Center, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Dermatopathology, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Dermatopathology, Razi Dermatology Hospital, Tehran University of Medical Sciences; Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication5-Dec-2016

Correspondence Address:
Alireza Ghanadan
Department of Dermatopathology, Razi Dermatology Hospital, Vahdate Eslami Street, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-6029.195221

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  Abstract 


Introduction: Neutrophilic dermatosis (ND) is a heterogeneous group of diseases with various etiologies and clinical presentations. NDs may clinically present as papule, vesiculopustule, plaque, and nodule of the skin, but they all share the common feature of neutrophilic predominance in the skin. Histological examination of patients with suspected ND is a key step for making the proper diagnosis. Patients and Methods: The aim of this article was to investigate histopathological aspects of different NDs. We obtained our data from medical records of patients at Razi dermatology hospital, between 2012 and 2014. Thirty-eight biopsy records coded under the term of any ND, including Sweet's syndrome (SS), pyoderma gangrenosum (PG), skin lesions of Behcet's disease, neutrophilic drug eruption, amicrobial pustulosis of the folds, pustular vasculitis of the hands, and undetermined ND were recruited in our study. The specimens were evaluated regarding inflammatory reaction pattern, epidermal/adnexal changes, and dermal changes. Results: Most common NDs in our study were PG (42.1%) followed by SS (21.1%). The most common pattern of inflammatory reaction was superficial perivascular and interstitial dermal inflammation in 44.7% of the patients. Exocytosis of neutrophils into epidermis, hair follicle, and eccrine gland was seen in 71%, 18.5%, and 28.9% of the specimens, respectively. Ulceration was only seen in ten PG specimens. Dermal fibrosis and vascular proliferation were reported in all PG patients. Conclusion: The prevalence of some histopathological findings in different types of ND was significantly different. These features seem helpful in distinguishing between different NDs.

Keywords: Behcet's disease, histopathology, neutrophilic dermatosis, pyoderma gangrenosum, Sweet's syndrome


How to cite this article:
Ehsani AH, Aghazadeh N, Dadkhahfar S, Khezri S, Mirzaei M, Ghanadan A. Histopathological aspects of neutrophilic dermatoses: Investigation of 38 cases and review of the literature. Indian J Dermatopathol Diagn Dermatol 2016;3:45-51

How to cite this URL:
Ehsani AH, Aghazadeh N, Dadkhahfar S, Khezri S, Mirzaei M, Ghanadan A. Histopathological aspects of neutrophilic dermatoses: Investigation of 38 cases and review of the literature. Indian J Dermatopathol Diagn Dermatol [serial online] 2016 [cited 2020 Oct 28];3:45-51. Available from: https://www.ijdpdd.com/text.asp?2016/3/2/45/195221




  Introduction Top


Neutrophilic dermatosis (ND) is a heterogeneous group of skin diseases with various etiologies and clinical presentations. All diseases classified under the group of ND share the common feature of neutrophil predominance in dermis.[1] Various skin lesions such as papule, vesiculopustule, plaque, and nodule may be seen in these diseases. NDs are categorized according to the clinical presentation and underlying etiology.[2]

The pathogenesis of NDs remains inclusive; however, some theories have been suggested. An alternation in the function of the immune system has been most commonly proposed [3] as evidenced by the dramatic response of these disorders to the administration of systemic corticosteroids. T-cell cytokines including interleukin-1 and immune complexes possibly play a role in the pathophysiology of ND.[4],[5],[6]

Considering the heterogeneous presentation of NDs, the histopathological evaluation of skin lesions seems to be crucial for making the correct diagnosis. Well-defined NDs include Sweet's syndrome (SS), pyoderma gangrenosum (PG), some lesions of Behcet's disease, and amicrobial pustulosis of folds.[7] SS and PG are the most prevalent diseases in this group. SS was first introduced by Sweet in 1964.[8] Classic forms of SS are characterized by fever and abrupt onset of papule, plaque, or nodules, usually on the upper extremity, face, and neck and typically associated with fever and peripheral blood neutrophilia. Histopathological evaluation shows neutrophilic infiltration which is mainly found in the upper dermis. The involvement of other organs is not uncommon.[9] PG is an inflammatory neutrophilic disease with both systemic and skin involvement.[10] PG is thought to be a neutrophilic dyscrasia caused by the exaggerated release of cytokines as a result of immune reaction.[11] The release of anti-matrix metalloproteinase and tumor necrosis factor alpha can trigger ulceration of the primary lesion of PG.[12] Similar lesion to SS and PG and pathergy test-related lesion in Behcet's disease are also categorized as ND.[7],[13]

Due to the heterogeneity of disorders in ND group, careful evaluation and diagnosis is of great importance. Identifying characteristic histopathologic findings is valuable for diagnosing the underlying disease properly. Our study was designated to investigate the histopathological aspects of NDs in patients and help classify and diagnose different NDs more efficiently.


  Patients and Methods Top


This was a cross-sectional retrospective study. We obtained our data from the medical records of patients at the Dermatopathology Department of Razi Dermatology Hospital, Tehran, between 2012 and 2014. All biopsy records of patients coded under the term of any ND, including SS, PG, skin lesions of Behcet's disease, neutrophilic drug eruption, amicrobial pustulosis of the folds, pustular vasculitis of the hands, and undetermined ND were recruited in our study. [Table 1] summarizes the patients' clinical information and demographic data.
Table 1: Clinical data and associated conditions of 38 patients with neutrophilic dermatosis in Razi hospital

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The paraffin-embedded standard hematoxylin and eosin-stained biopsies of patients were evaluated regarding inflammatory reaction pattern, epidermal/adnexal changes, and dermal changes.

We classified the histopathologic features of specimens with neutrophilic dermal infiltration into the following three groups: Superficial perivascular, superficial perivascular/interstitial, and superficial and deep perivascular/interstitial. Categorization of the inflammatory cell type including lymphocyte, histiocyte, lymphocyte, eosinophil, and plasma cell was considered for the non-neutrophilic infiltrations. We investigated the presence of ulceration and exocytosis of neutrophil to epidermis, hair follicle, and eccrine glands. Vascular changes including vasculopathy, vasculitis, fibrosis, vascular proliferation, and leukocytoclasia were noted. Panniculitis was categorized as septal or mixed septal/lobular. In addition, the presence of collagen degeneration, dermal edema, and dermal abscess was documented.

The data were collected and computerized. Descriptive statistics and percentage frequencies were calculated and analyzed with SPSS 22 (IBM SPSS Statistics V22.0).


  Results Top


Thirty-eight patients with various types of ND were enrolled in our study. The most common diagnosis was PG (42.1%) followed by SS (21.1%). Seven patients (18.4%) had ND due to underlying Behcet's disease. Four patients (10.5%) were diagnosed with neutrophilic drug eruption. Least common diseases were pustular vasculitis of the hands, amicrobial pustulosis of the folds, and undetermined ND [Figure 1]. Demographic and clinical data with associated conditions are summarized in [Table 1] and [Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6]. The histopathological findings in our study were described under three sections: Inflammatory reaction pattern, epidermal/adnexal changes, and dermal changes [Figure 7].
Figure 1: Prevalence of different types of neutrophilic dermatosis in 38 cases in Razi Hospital

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Figure 2: Pyoderma gangrenosum. Large superficial ulcer of the right trunk in a 56-year-old male several months ago with a history of pyoderma gangrenosum and a cribriform scar on the left chest wall (case 3) (H and E, × 10)

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Figure 3: (a) Pyoderma gangrenosum. Large deep ulcer with erosion and crust in the forearm of a 43-year-old female 3 months ago (case 15). (b) Leukocytoclastic vasculitis with neutrophilic infiltration and nuclear debris along with fibrinoid necrosis in vessel walls in pyoderma gangrenosum (H and E, × 20)

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Figure 4: Sweet's syndrome. (a) Painful erythematous plaques on the back (case 18). (b). Leukocytoclastic vasculitis with neutrophilic infiltration and fibrinoid necrosis in Sweet's syndrome (H and E, × 20)

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Figure 5: Behcet's disease. (a) Erythematous papules and pustules of the lower limb (case 30). (b) Leukocytoclastic vasculitis with fibrinoid necrosis of the vessels (H and E, × 20)

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Figure 6: Neutrophilic drug eruption. (a) Erythematous macules and plaques of the back (case 33). (b) Intraepidermal pustule formation with leukocytoclastic vasculitis and dermal edema (H and E, × 20)

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Figure 7: Distribution of vasculopathy, vasculitis, fibrosis, and vascular proliferation in different types of neutrophilic dermatosis

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Inflammatory reaction pattern

Patterns of inflammatory reaction included superficial perivascular and interstitial dermal inflammation in 17 patients (44.7%) and also superficial and deep perivascular/interstitial inflammation in 15 patients (39.5%). However, six patients (15.8%) merely showed superficial perivascular inflammation.

The density of neutrophilic infiltration was mild/moderate in 24 specimens and severe in 14 cases. Severe neutrophilic density was mostly seen in PG, followed by Behcet's disease and SS. Lymphocytes were the most common cells to cause non-neutrophilic infiltration in our patients (42.1%). Histiocyte and plasma cell infiltration was seen only in PG [Table 2].
Table 2: Patterns of inflammation in 38 patients with neutrophilic dermatosis in Razi hospital

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Epidermal and adnexal changes

Neutrophilic epidermotropism or exocytosis of neutrophils into epidermis was seen in 27 (71%) cases. This resulted in epidermal abscess formation in 10 patients (26.3%). Neutrophilic folliculotropism or exocytosis of neutrophils into hair follicles was observed in 7 (18.5%) patients. However, follicular abscess was reported only in two patients (5.25%). Eleven specimens (28.9%) showed neutrophilic eccrinotropism or exocytosis of neutrophils into the eccrine glands. Ulceration was seen in ten specimens (26.3%), and all the biopsies that showed ulceration were diagnosed with PG (P < 0.001) [Table 3].
Table 3: Patterns of epidermal and adnexal changes in 38 patients of neutrophilic dermatosis

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Dermal changes

Dermal changes are illustrated in [Table 4]. Vasculopathy and vasculitis were observed in 16 (42.1%) and 19 (50%) cases, respectively. Among those with vasculitis, nine cases were diagnosed with PG. Five (26.3%) and 3 (15.8%) patients were associated with Behcet's disease and SS, respectively. The remaining two were cases of neutrophilic drug eruption and pustular vasculitis of the hands. Signs of fibrosis and vascular proliferation were seen in all patients who were diagnosed with PG. None of the patients with other diagnosis had this feature (P < 0.0001) [Figure 7].
Table 4: Patterns of dermal changes in 38 patients of neutrophilic dermatosis

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Leukocytoclasia was observed in 22 (57.9%) biopsy specimens in our study. Leukocytoclasia was severe in seven patients. Progression of dermal inflammation into deep layers caused panniculitis in 9 (23.7%) patients. Superficial dermal edema was observed in twenty (52.6%) specimens. Dermal abscess was reported only in two patients (5.3%), of which both were diagnosed by PG.


  Discussion Top


To the best of our knowledge, the current study is among few to describe the histological features of various NDs in a considerable number of patients. NDs are heterogeneous both in clinical presentation and underlying etiology, so histological evaluation is necessary for an exact diagnosis.[14] The most common types of NDs in our study were PG and SS.

Since the first description of SS by Dr. Sweet, hundreds of cases have been reported in literature.[7] Skin biopsy is usually necessary in the diagnosis of SS. Histopathological findings of SS include diffuse dermal neutrophilic infiltration with variable degrees of dermal edema. Dermal infiltration of neutrophils can be diffuse and pan-dermal or perivascular with the occasional involvement of follicles and eccrine glands. Superficial dermal edema is a common finding in SS.[15] In our study, mild/moderate and severe neutrophilic infiltrations were seen in five and three patients, respectively, out of the eight cases with SS. Involvement of follicles or eccrine glands was not observed in any of the patients with SS.

Historically, it was believed that no true vasculitis should be seen when the diagnosis of SS is suggested,[16] but several observations showed that true vasculitis can be encountered in SS.[17] Our findings revealed that three out of eight patients with SS had signs of vasculitis with fibrinoid necrosis. The current study confirmed that existence of vasculitis cannot rule out the diagnosis of SS.

PG was the most frequently diagnosed ND in our patients. Regardless of the underlying etiology of PG, fibrosis and vascular proliferation and ulceration were seen in all cases. No other diagnosis was associated with these features. Histopathological findings of PG tend to be different according to the type of PG, duration of the lesion, and site of biopsy.[18] As it has been illustrated in the earlier studies, the primary lesions of PG can be similar to SS.[19] Our study confirmed that many features such as heavy dermal infiltration, leukocytoclasia, and vasculopathy are prominent in both SS and PG. However, vascular proliferation and fibrosis can be pathognomonic of PG. Dermal edema was found occasionally in PG specimens. Abscess formation was seen in only two specimens, both of which were diagnosed with PG. In our study, more than half of the patients with PG showed vasculitis. This finding was compatible with previous studies that mention a variable degree of vascular damage in PG such as focal vasculitis in well-developed lesions.[20],[21]

Panniculitis was the feature most commonly encountered in patients with SS and PG in our study. Although panniculitis is observed frequently in ND, it should be differentiated from neutrophilic panniculitis, a condition also referred to as subcutaneous SS.[22]

In our study, vasculitis was observed in more than half of the patients with Behcet's disease. Leukocytoclasia along with dermal edema was the other prominent feature. However, the other characteristics of ND such as epidermotropism and adnexal involvement were not frequently observed in this type of ND. It has been proposed that the earlier lesions of Behcet's disease show neutrophilic vascular reaction while the older lesions have perivascular lymphocytic infiltration.[23] The type of non-neutrophilic infiltrate in Behcet's disease cases in our study was lymphocyte and histiocyte in five out of seven patients.


  Conclusion Top


Histological examination of patients with suspected neutrophilic dermatoses is a key step for proper diagnosis of the underlying etiology. This finally results in timely diagnosis and eventually better management of ND patients. Identifying the histopathological features of each type of ND is necessary to reach this goal. Our study revealed some histopathological findings that are helpful in distinguishing between NDs. Ulceration, dermal fibrosis, and vascular proliferation were most commonly seen in PG.

Financial support and sponsorship

This research has been supported by Tehran University of Medical Sciences and Health Services, grant 21881.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Callen JP. Neutrophilic dermatoses. Dermatol Clin 2002;20:409-19.  Back to cited text no. 1
    
2.
James WD. Newer neutrophilic dermatoses. Arch Dermatol 2003;139:101-2.  Back to cited text no. 2
    
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Cohen PR. Neutrophilic dermatoses: A review of current treatment options. Am J Clin Dermatol 2009;10:301-12.  Back to cited text no. 3
    
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Sailler L, Joseph-Hein K, Astudillo L, Madaule S, Ecoiffier M, Dahan S, et al. Pustular vasculitis in a patient with T-cell large granular lymphocyte proliferation and myelodysplasia. Successful treatment by cyclosporin. Br J Dermatol 2003;149:893-4.  Back to cited text no. 4
    
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Jorizzo JL, Schmalstieg FC, Dinehart SM, Daniels JC, Cavallo T, Apisarnthanarax P, et al. Bowel-associated dermatosis-arthritis syndrome. Immune complex-mediated vessel damage and increased neutrophil migration. Arch Intern Med 1984;144:738-40.  Back to cited text no. 5
    
6.
Jones JL, Fletcher A, Graham-Brown RA. An immunohistochemical study of the dermal infiltrate and epidermal staining for interleukin 1 in 12 cases of Sweet's syndrome. Br J Dermatol 1996;134:705-9.  Back to cited text no. 6
    
7.
Bonamigo RR, Razera F, Olm GS. Neutrophilic dermatoses: Part I. An Bras Dermatol 2011;86:11-25.  Back to cited text no. 7
    
8.
Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol 1964;76:349-56.  Back to cited text no. 8
    
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Fitzgerald RL, McBurney EI, Nesbitt LT Jr. Sweet's syndrome. Int J Dermatol 1996;35:9-15.  Back to cited text no. 9
    
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Farhi D, Wallach D, Avril MF. Pyoderma gangrenosum is 100 years old. From Louis Brocq to biotherapies. Rev Prat 2008;58:457-61.  Back to cited text no. 10
    
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Hasselmann DO, Bens G, Tilgen W, Reichrath J. Pyoderma gangrenosum: Clinical presentation and outcome in 18 cases and review of the literature. J Dtsch Dermatol Ges 2007;5:560-4.  Back to cited text no. 11
    
12.
Brooklyn TN, Williams AM, Dunnill MG, Probert CS. T-cell receptor repertoire in pyoderma gangrenosum: Evidence for clonal expansions and trafficking. Br J Dermatol 2007;157:960-6.  Back to cited text no. 12
    
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Jorizzo JL, Abernethy JL, White WL, Mangelsdorf HC, Zouboulis CC, Sarica R, et al. Mucocutaneous criteria for the diagnosis of Behçet's disease: An analysis of clinicopathologic data from multiple international centers. J Am Acad Dermatol 1995;32:968-76.  Back to cited text no. 13
    
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Alavi A, Sajic D, Cerci FB, Ghazarian D, Rosenbach M, Jorizzo J. Neutrophilic dermatoses: An update. Am J Clin Dermatol 2014;15:413-23.  Back to cited text no. 14
    
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Saavedra AP, Kovacs SC, Moschella SL. Neutrophilic dermatoses. Clin Dermatol 2006;24:470-81.  Back to cited text no. 15
    
16.
Parsapour K, Reep MD, Gohar K, Shah V, Church A, Shwayder TA. Familial Sweet's syndrome in 2 brothers, both seen in the first 2 weeks of life. J Am Acad Dermatol 2003;49:132-8.  Back to cited text no. 16
    
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Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis update: Diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. Am J Dermatopathol 2005;27:504-28.  Back to cited text no. 17
    
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Duguid CM, Powell FC. Pyoderma gangrenosum. Clin Dermatol 1993;11:129-33.  Back to cited text no. 18
    
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Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: Pyoderma gangrenosum and Sweet's syndrome. Postgrad Med J 1997;73:65-8.  Back to cited text no. 19
    
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Ahronowitz I, Harp J, Shinkai K. Etiology and management of pyoderma gangrenosum: A comprehensive review. Am J Clin Dermatol 2012;13:191-211.  Back to cited text no. 20
    
21.
Poewll FC, Hackett BC, Wallach D. Pyoderma gangrenosum. In: Goldsmith LA, Fitzpatrick TB, editors. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw-Hill Professional; 2012. p. 371-80.  Back to cited text no. 21
    
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23.
Alpsoy E, Uzun S, Akman A, Acar MA, Memisoglu HR, Basaran E. Histological and immunofluorescence findings of non-follicular papulopustular lesions in patients with Behçet's disease. J Eur Acad Dermatol Venereol 2003;17:521-4.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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