Skin nontumor

Dermal perivascular and vasculopathic reaction patterns

Dermal hypersensitivity reaction

Editorial Board Member: Viktoryia Kazlouskaya, M.D., Ph.D.
Jiejun Wu, M.D., Ph.D.
Maxwell A. Fung, M.D.

Last author update: 30 September 2021
Last staff update: 23 January 2023

Copyright: 2021-2023,, Inc.

PubMed Search: Dermal hypersensitivity reaction pathology review [PT]

Jiejun Wu, M.D., Ph.D.
Maxwell A. Fung, M.D.
Page views in 2022: 6,614
Page views in 2023 to date: 821
Cite this page: Wu J, Fung MA. Dermal hypersensitivity reaction. website. Accessed February 8th, 2023.
Definition / general
Essential features
  • Sparse to moderately dense superficial and mid perivascular and interstitial lymphocytic infiltrate with eosinophils
  • Epidermal changes may be absent, minimal (spongiotic or vacuolar interface) or secondary (excoriation)
  • Comparable or equivalent histologic terms: cutaneous hypersensitivity reaction / response, dermal hypersensitivity response, urticarial hypersensitivity reaction
  • For idiopathic pruritic skin conditions, some clinicians include dermal hypersensitivity reaction in their clinical differential diagnosis
  • Similar or equivalent terms: itchy red bump disease, papular dermatitis, subacute prurigo and urticarial dermatitis
  • Note: papular urticaria is a synonym for arthropod bite reactions; drug induced hypersensitivity syndrome (DIHS) is a specific type of drug reaction
ICD coding
  • ICD-10:
    • L30.8 - other specified dermatitis
    • L30.9 - dermatitis, unspecified
  • Idiopathic until or unless confirmed to be other entities based on clinical correlation (see Differential diagnosis)
Clinical features
  • Histologic reaction pattern that must be confirmed microscopically but the final diagnosis requires clinical correlation
  • Deeper tissue sections to rule out other diagnoses may be needed; e.g., folliculitis, spongiotic dermatitis, scabies may become apparent only in deeper sections
  • Exceptionally, may be a paraneoplastic hypersensitivity reaction (J Am Acad Dermatol 2010;63:e13, Clin Exp Dermatol 2016;41:322)
  • No laboratory requests are mandated but screening for evidence of specific causes may be prudent (see Differential diagnosis)
  • Ancillary testing may include a second biopsy for direct immunofluorescence (DIF) testing, scabies prep, complete blood count (CBC) or other serologic studies (J Am Acad Dermatol 2014;70:263)
Prognostic factors
  • Idiopathic cases have chronic course with potentially unsatisfactory responses to treatment (see Treatment)
  • No reported impact on life expectancy in idiopathic cases
Case reports
Clinical images

Contributed by Maxwell A. Fung, M.D.

Crusted papules coalescing into plaques

Papules and lichenified plaques

Multiple papules on the leg

Urticarial papules and plaques

Microscopic (histologic) description
  • Superficial and mid dermal perivascular and interstitial infiltrate involving the superficial (papillary) and mid (upper reticular) dermis; may extend to deep reticular dermis
  • Predominantly lymphocytic infiltrate with eosinophils; with or without neutrophils
  • Varying intensity of infiltrate, typically sparse to moderately dense
  • Epidermal alteration, if present, may consist of minimal parakeratosis, spongiosis, vacuolar interface changes or secondary crust / excoriation
  • References: J Am Acad Dermatol 2002;47:898, Arch Dermatol 2006;142:29, J Am Acad Dermatol 2014;70:263
Microscopic (histologic) images

Contributed by Maxwell A. Fung, M.D.

Itchy red bump disease

Atopic dermatitis

Urticarial dermatitis


Perivascular dermatitis, invisible dermatoses and sclerosing disorders

Sample pathology report
  • Example #1 (circa 2001, University of Connecticut)
    • Clinical information: rule out hypersensitivity reaction
    • Specimen / site: left upper arm
    • Diagnosis: dermal hypersensitivity reaction (see comment)
    • Comment: Deeper sections have been performed. The histological differential diagnosis includes a lesion of urticaria. There is a sparse superficial and mid dermal perivascular infiltrate composed of lymphocytes, histiocytes, neutrophils and eosinophils.

  • Example #2 (circa 1998, Cornell University Medical Center)
    • Superficial and deep perivascular dermatitis, consistent with a dermal hypersensitivity reaction, biopsy:
      • T-01000; T-02471; M-40006
      • ICD-9: V72.6 and 693.89
      • Comment: A reaction to an internal antigen source seems likely because of the deep inflammation; however, slight spongiosis is noted and chronic allergic contact dermatitis cannot be completely ruled out histologically.

  • Example #3 (circa 2020, University of California Davis)
    • Skin, right posterior forearm, punch biopsy:
      • Sparse dermatitis with eosinophils and mild spongiosis (see comment)
      • Comment: The histologic differential diagnosis includes a drug reaction or spongiotic / eczematous dermatitis, as well as a sparse arthropod bite or other hypersensitivity reaction. There is focal epidermal necrosis consistent with external trauma. Overt fungi on H&E is not visible; a fungal stain may be obtained upon request if necessary.

  • Example #4 (circa 2020, University of California Davis)
    • Skin, mid back, punch biopsy:
      • Sparse perivascular and interstitial dermatitis with eosinophils (see comment)
      • Comment: The histologic differential diagnosis includes a drug or other hypersensitivity reaction, nondiagnostic spongiotic / eczematous dermatitis or as a diagnosis of exclusion, an idiopathic eruption (e.g., itchy red bump disease, urticarial dermatitis). Some eosinophils are present near the dermal epidermal junction, so urticarial pemphigoid could also be considered (but not specifically favored). Deeper sections fail to reveal additional findings.
Differential diagnosis
  • Differential diagnosis of dermal hypersensitivity reaction is broad; clinical correlation is required in all instances
  • Drug eruption:
    • Subtle vacuolar interface changes or spongiosis are often present
  • Arthropod bite reaction (papular urticaria):
    • Infiltrates tend to be deeper and denser with abundant eosinophils; may involve subcutis; may show centrally positioned intraepidermal vesicle or crusted erosion / ulcer (punctum)
    • Clinically, the lesions should be exclusively papules, erythematous and usually edematous / urticarial and tend to occur either as a single or localized cluster of papules on the extremities, ideally with a patient confirmed mosquito, flea, mite or other arthropod exposure
  • Atopic dermatitis:
    • Biopsies of atopic dermatitis usually present as spongiotic dermatitis so more prominent spongiosis, such as spongiotic vesicles and confluent or diffuse parakeratosis, would support this possibility
    • Clinically, patients present with eczematous skin plaques or papules and a personal or history of atopy; diagnostic criteria (Hanifin-Rajka) for atopic dermatitis may be applied by the clinician
  • Contact dermatitis:
    • Biopsies of contact dermatitis usually present as spongiotic dermatitis, so more prominent spongiosis, such as spongiotic vesicles and confluent or diffuse parakeratosis, would support this possibility
    • Clinically, allergens or irritants may be confirmed by clinical history or patch testing
  • Spongiotic / eczematous dermatitis, NOS:
    • Dermal hypersensitivity reaction with more prominent spongiosis, such as spongiotic vesicles and confluent or diffuse parakeratosis, would support this possibility
    • Clinical correlation is required to confirm a specific type of spongiotic / eczematous dermatitis (e.g., atopic, contact, nummular)
  • Urticaria:
    • Dermal hypersensitivity reaction with no epidermal changes at all; dermal edema and neutrophils typically present in addition to the lymphocytes and eosinophils
  • Pruritic urticarial papules and plaques of pregnancy (PUPPP):
    • Dermal hypersensitivity reaction, sometimes with more prominent spongiosis and marked papillary dermal edema
  • Associated with malignancy or other systemic conditions:
  • Urticarial vasculitis:
    • In addition to clinical correlation, evidence of vasculitis from another biopsy or a positive direct immunofluorescence (DIF) result would typically be required
  • Bullous pemphigoid:
    • Infiltrate of eosinophils centered upon the dermoepidermal junction and within the epidermis (eosinophilic spongiosis) would be typical of the urticarial or prebullous phase of pemphigoid
    • Positive DIF result from perilesional skin would be required
  • Scabies:
    • Crust and prominent eosinophils are typical
    • Deeper sections, multiple biopsies or scabies prep may be required to identify diagnostic findings (mite, eggs, feces [scybala])
  • Wells syndrome (eosinophilic cellulitis) and other eosinophil predominant infiltrates:
    • Dermal hypersensitivity reaction must contain eosinophils but the infiltrate is predominately lymphocytic (Dermatol Clin 2012;30:667)
    • Flame figures typify Wells syndrome but may be present occasionally in any eosinophil rich dermal infiltrate
  • Viral exanthem:
    • Vacuolar interface dermatitis, often with extravasated erythrocytes and exocytosis of lymphocytes, often accompanies sparse dermal infiltrates
    • Eosinophils are not specifically characteristic of a viral exanthem but would not exclude this possibility
Board review style question #1

Which of the following histologic findings is required for the diagnosis of dermal hypersensitivity reaction?

  1. Eosinophils
  2. Granulomas
  3. Neutrophils
  4. Plasma cells
  5. Spongiosis
Board review style answer #1
A. Eosinophils. Required histologic features of dermal hypersensitivity reaction include a perivascular and interstitial lymphocytic infiltrate with eosinophils. Neutrophils and spongiosis are variable but not required findings. Granulomas and plasma cells are not features of dermal hypersensitivity reaction.

Comment Here

Reference: Dermal hypersensitivity reaction
Board review style question #2
A punch biopsy of a pruritic eruption of 5 years duration involving the trunk of a 64 year old man is reported as a dermal hypersensitivity reaction. The pathologist commented that deeper sections were negative. The microscopic description documents scant parakeratosis and spongiosis. Which of the following may be considered in the differential diagnosis?

  1. Folliculitis
  2. Sarcoid
  3. Syphilis
  4. Urticaria
  5. Urticarial dermatitis
Board review style answer #2
E. Urticarial dermatitis. The negative deeper sections are against folliculitis. Sarcoid would require granulomas which are not a feature of dermal hypersensitivity reaction. Syphilis typically shows a psoriasiform lichenoid pattern with plasma cells. The parakeratosis and spongiosis excludes urticaria.

Comment Here

Reference: Dermal hypersensitivity reaction
Back to top
Image 01 Image 02