Neutrophilic Urticarial Dermatosis Without Underlying Systemic Disease

| March 1, 2020

J Clin Aesthet Dermatol. 2020;13(3):20–21

by Ryan Gillihan, MD; Navid Farahbakhsh, MCE; and Kiran Motaparthi, MD

Drs. Gillihan and Motaparthi are with the Department of Dermatology at the University of Florida in Gainesville, Florida. Mr. Farahbakhsh is with the University of Florida College of Medicine in Gainesville, Florida.

FUNDING: No funding was provided for this study.

DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article.

ABSTRACT: Neutrophilic urticarial dermatosis (NUD) is rare and poorly understood. First described in 2009, NUD has been reported in association with systemic and autoinflammatory disorders. Here, we describe an example of NUD occurring in the absence of underlying systemic findings that showed an excellent response to low-dose dapsone.

Key words: Dapsone, neutrophilic urticarial dermatosis, urticaria


Neutrophilic urticarial dermatosis (NUD) is a rare and poorly understood dermatologic condition. NUD was first described by Kieffer et al,1 who identified a subset of patients with urticarial eruptions, that histopathologically demonstrated a perivascular and interstitial neutrophilic infiltrate with leukocytoclasia without frank vasculitis or dermal edema.1 All cases of NUD previously described in the literature were reported in patients with concurrent systemic symptoms, such as polyarthritis or fever. Although rare, NUD can occur without a specific associated underlying disease; however, systemic indices of inflammation are typically elevated. The case described here is unique due to the isolated clinicopathologic features of NUD without associated underlying systemic disease.

Case Presentation

A 34-year-old male patient with no significant medical history presented with an eruption on his hands and forearms that had developed 10 days prior. Individual lesions had resolved spontaneously within 24 to 48 hours, but were associated with a burning sensation and mild pruritus not relieved by oral diphenhydramine or hydrocortisone 1% cream. On physical examination, scattered, light pink, targetoid urticarial patches and plaques were observed on the dorsal aspect of both hands (Figure 1A). Physical exam was unremarkable, and the patient did not report fevers, malaise, or arthralgia. Several days after initial presentation to the clinic, the eruption became widespread, involving the arms, neck, chest, and back (Figure 1B).

Telescoping punch biopsy was performed, and histopathology demonstrated an interstitial infiltrate of neutrophils with prominent epitheliotropism of the eccrine units and acrosyringia. Leukocytoclasia, without evidence of vasculitis, was also identified. Dermal edema was not observed (Figure 2).

Complete blood count, metabolic panel, antinuclear antibody, erythrocyte sedimentation rate, and C-reactive protein levels were all within normal limits. Dapsone 25mg daily was initiated, with a rapid response observed within 72 hours. Within four weeks, the patient reported complete clearance.

Discussion

NUD requires clinical and histologic distinction from conventional urticaria, urticarial vasculitis, drug eruptions, and neutrophilic dermatoses, such as Sweet syndrome. Compared to conventional urticaria, NUD is associated with dysesthesia, rather than significant pruritus, and is not responsive to antihistamines. Unlike urticarial vasculitis, drug eruptions, and neutrophilic dermatoses (e.g., Sweet syndrome), NUD typically resolves within 24 to 48 hours.2 To date, patients with NUD were described to have concurrent systemic symptoms, such as polyarthritis or fever. Associated systemic diseases include adult-onset Still disease, systemic lupus erythematosus, Schnitzler syndrome, primary biliary cirrhosis, Sjögren’s syndrome, inflammatory bowel disease, and cryopyrin-associated periodic syndromes (CAPS).1,2,3,6 A recent case series described NUD in children as a presenting feature of systemic juvenile idiopathic arthritis.4

Several subtle but important histologic findings permit the differentiation of NUD from neutrophilic and conventional urticaria, drug eruptions, and leukocytoclastic vasculitis. Neutrophilic epitheliotropism, the identification of neutrophils within the epidermis or adnexae, is a sensitive and specific histologic clue that permits differentiation of NUD from neutrophilic urticaria.2 Relative to conventional urticaria and drug eruptions, the inflammatory infiltrate of NUD lacks eosinophils and papillary dermal edema. An absence of vacuolar interface change with basilar keratinocyte necrosis in NUD permits distinction from drug eruptions as well. Finally, despite the presence of leukocytoclasia in NUD, there is no frank vessel wall necrosis as observed in leukocytoclastic vasculitis.2

In the setting of lupus erythematosus, NUD might be mistaken as a “lupus flare,” prompting immunosuppressive therapy. However, prednisone, methotrexate, hydroxychloroquine, mycophenolate mofetil, and azathioprine do not improve the cutaneous lesions of NUD.1,2,3 Antihistamines are also typically ineffective.2 The most effective therapies are neutrophil migration inhibitors, such as colchicine 0.5 to 1.0mg/day and dapsone 50 to 200mg/day.1,3 NUD is also responsive to interleukin-1 antagonists, such as anakinra, particularly in the context of CAPS.2,6

Conclusion

In conclusion, NUD is typically diagnosed within the context of systemic disease or inflammatory markers. Rarely, NUD can occur as an isolated entity. Histopathology, clinical morphology, symptomatology, and a lack of response to antihistamines are helpful in discriminating NUD from conventional or neutrophilic urticaria, drug eruption, or vasculitis. Distinction from these simulators with overlapping clinicopathologic features is worthwhile, given the excellent response to nonimmunosuppressive agents targeting neutrophils.

References

  1. Kieffer C, Cribier B, Lipsker D. Neutrophilic urticarial dermatosis: a variant of neutrophilic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature. JAMA Dermatol. 2009;88(1):23–31.
  2. Broekaert SMC, et al. Neutrophilic epitheliotropism is a histopathological clue to neutrophilic urticarial dermatosis. Am J Dermatopathol. 2016;38(1): 39–49.
  3. Gusdorf L, Bessis D, Lipsker D. Lupus erythematosus and neutrophilic urticarial dermatosis: a retrospective study of 7 patients. Medicine (Baltimore). 2014;93(29):e351.
  4. Stringer T, Gittler J, Meehan S, et al. Neutrophilic urticarial dermatosis as a presenting feature of systemic juvenile idiopathic arthritis. Pediatr Dermatol. 2018;35(3):e170–e172.
  5. Saeb-Lima M, Charli-Joseph Y, Rodriguez-Acosta E, et al. Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus. Am J Dermatopathol. 2013;35(6):655–660.
  6. Kolivras A, Theunis A, Ferster A, et al. Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement. J Cutan Pathol. 2011;38(2):202–208.

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Category: Case Report, Current Issue

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