Skin nontumor
Dermal granulomatous and necrobiotic reaction patterns
Reactive granulomatous dermatitis
Last author update: 24 March 2022
Last staff update: 8 August 2022
Note: Drs. Aghighi and Turner are both first authors on this topic
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PubMed Search: Reactive granulomatous dermatitis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Aghighi M, Turner N, Motaparthi K. Reactive granulomatous dermatitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorinterstitialgranulomatous.html. Accessed August 10th, 2022.
Definition / general
- Dermal reaction pattern associated with autoimmune processes more often than infection or malignancy
- Spectrum of clinicopathologic features that vary with lesion age
- Comprises lesions consistent with palisaded neutrophilic granulomatous dermatitis and interstitial granulomatous dermatitis
Essential features
- Dermal reaction pattern associated with a systemic process, most commonly an autoimmune disease
- Variable clinical presentations including crusted pink-brown papules and plaques on extensor extremities, umbilicated papules on acral site, annular plaques on trunk and indurated linear cords on flanks
- Variable pathologic features including degenerated collagen surrounded by palisades of histiocytes, neutrophils and eosinophils, necrobiotic rosettes and leukocytoclastic vasculitis
- Commonly resolves with management of associated systemic disease
Terminology
- Interstitial granulomatous dermatitis, palisaded neutrophilic granulomatous dermatitis, Winkelmann granuloma, superficial ulcerating rheumatoid necrobiosis
ICD coding
- ICD-10: L92.9 - granulomatous disorder of the skin and subcutaneous tissue, unspecified
Epidemiology
- F > M; adults > children
- Associated with autoimmune disorders > malignancies or infections (Hum Pathol 2014;45:598, JAAD Case Rep 2017;3:425)
- Palisaded neutrophilic granulomatous dermatitis pattern is most commonly associated with rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis
- Interstitial granulomatous dermatitis pattern is most commonly associated with rheumatoid arthritis (RA), seronegative inflammatory arthritis and autoimmune thyroiditis (Arch Dermatol 1994;130:1278)
- Less common associations include malignant processes (e.g., myelodysplastic syndrome and myeloid leukemia), infections (e.g., human immunodeficiency virus [HIV], Epstein-Barr virus [EBV], parvovirus B19 and Streptococcus), autoimmune diseases (including systemic sclerosis and inflammatory bowel disease) and metabolic diseases (including diabetes) (Dermatol Clin 2015;33:373, Clin Case Rep 2019;7:695)
Sites
- Interstitial granulomatous dermatitis: lateral upper trunk, flanks, buttocks and proximal limbs
- Palisaded neutrophilic granulomatous dermatitis: extensor surfaces of extremities
Pathophysiology
- Poorly understood but thought to be caused by immune complex deposition in small blood vessels → vasculitis, local ischemia and collagen degeneration → lymphohistiocytic response (Am J Clin Dermatol 2010;11:171)
Clinical features
- Palisaded neutrophilic granulomatous dermatitis: red crusted or umbilicated papules, plaques and nodules symmetrically distributed and typically on extensor surfaces
- Interstitial granulomatous dermatitis: firm linear cords or annular erythematous plaques on lateral upper trunk, buttocks and proximal limbs
- Usually asymptomatic but may be pruritic or tender
- Significant overlap between palisaded neutrophilic granulomatous dermatitis and interstitial granulomatous dermatitis; lesions consistent with both entities may present in the same patient
- Reference: Dermatol Clin 2015;33:373
Diagnosis
- Clinical features including history of systemic disease
- Punch biopsy
- Reference: Dermatol Clin 2015;33:373
Prognostic factors
- Self resolving (up to 80%) more often than a chronic course (J Eur Acad Dermatol Venereol 2021;35:988)
- Related to activity of underlying systemic process
Case reports
- 47 year old woman with palisaded neutrophilic granulomatous dermatitis and Hodgkin lymphoma (Am J Dermatopathol 2019;41:835)
- 70 year old woman with reactive granulomatous dermatitis and rheumatoid arthritis (JAAD Case Rep 2016;2:67)
- 72 year old woman with reactive granulomatous dermatitis and myelodysplastic syndrome (Ann Hematol 2017;96:1037)
- 3 cases of generalized palisaded neutrophilic granulomatous dermatitis associated with chronic myelomonocytic leukemia (Hum Pathol 2017;64:198)
- 52 patients with reactive granulomatous dermatitis (J Eur Acad Dermatol Venereol 2021;35:988)
Treatment
- Management is focused on treatment of the underlying, triggering disorder
- No standardized lesion directed therapy
- Reports of improvement with topical corticosteroids, topical calcineurin inhibitors, systemic corticosteroids, tetracyclines, hydroxychloroquine, cyclosporin, etanercept and phototherapy (J Eur Acad Dermatol Venereol 2021;35:988)
Clinical images
Contributed by Christine J. Ko, M.D.
Upper extremity reactive granulomatous dermatitis
Symmetric upper
extremity reactive
granulomatous
dermatitis
Images hosted on other servers:
Plaque on thigh
Microscopic (histologic) description
- Inflammatory infiltrate is variable among lesions and as the lesions age (J Eur Acad Dermatol Venereol 2021;35:988, JAAD Case Rep 2017;3:425, Am J Dermatopathol 2015;37:614, Lupus 2016;25:209)
- May be consistent with classical palisaded neutrophilic granulomatous dermatitis or interstitial granulomatous dermatitis (see below) or may be neutrophil predominant, eosinophil predominant or histiocyte predominant
- Interstitial granulomatous dermatitis: small rosettes of necrobiotic collagen surrounded by histiocytes and lymphocytes (floating sign)
- Absent leukocytoclastic vasculitis and minimal or absent mucin deposition
- Scarce neutrophils and eosinophils
- Palisaded neutrophilic granulomatous dermatitis: large foci of necrobiotic collagen surrounded by palisades of histiocytes, lymphocytes and prominent neutrophils
- Leukocytoclastic vasculitis may be present in early lesions
- Mucin deposition is minimal or absent
Microscopic (histologic) images
Virtual slides
Images hosted on other servers:
Necrobiotic rosettes with histiocytes and neutrophils
Sample pathology report
- Upper trunk, punch biopsy:
- Reactive granulomatous dermatitis, eosinophil rich (see comment)
- Comment: There are palisades of histiocytes and eosinophils surrounding degenerated collagen in the superficial to mid dermis.
Differential diagnosis
- Interstitial granulomatous drug reaction:
- Firm papules, plaques and nodules that arise in response to exposure to medications, including antihypertensives, statins and tumor necrosis factor alpha inhibitors
- Presence of vacuolar interface dermatitis helps to differentiate from reactive granulomatous dermatitis
- Granuloma annulare:
- Firm, red-brown smooth or umbilicated papules, patches and subcutaneous nodules that arise most commonly on the extremities but may also be generalized
- Perforating variant may resemble umbilicated lesions of palisaded neutrophilic granulomatous dermatitis
- No clear association with autoimmune disease
- Abundant mucin and scarce neutrophils help to differentiate from reactive granulomatous dermatitis
- Infectious granuloma:
- Suppurative, sarcoidal or diffuse (interstitial) granulomas with positive infectious stains
- Rheumatoid nodules:
- Large nodules overlying extensor surfaces of joints in patients with rheumatoid arthritis
- Palisading granulomas with fibrinoid necrosis, prominent neutrophilic infiltrate and absent mucin deposition in deep dermis or subcutaneous fat
- Leukemia cutis:
- Reactive granulomatous dermatitis has been described in the setting of myelodysplastic syndrome and myeloid leukemia
- Distinguishing myeloid precursors from histiocytes enables differentiation
- Leukocytoclastic vasculitis:
- Purpuric macules and papules, petechiae, urticarial wheals and targetoid papules that favor dependent skin, are seen in small vessel vasculitis
- Small or medium sized vessels with fibrinoid necrosis, erythrocyte extravasation and neutrophilic perivascular infiltrate with karyorrhexis
- Lesions of palisaded neutrophilic granulomatous dermatitis may demonstrate leukocytoclastic vasculitis
- Reactive granulomatous dermatitis may occur in the setting of systemic vasculitides including granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis
- Acute febrile neutrophilic dermatosis (Sweet syndrome):
- Pink, tender edematous papules and plaques that favor the upper trunk; often with concomitant fever and variable systemic involvement
- Papillary dermal edema, dense neutrophilic infiltrate and karyorrhexis without vasculitis
Board review style question #1
A 55 year old woman with systemic lupus erythematosus presents with a 2 month history of pink-brown, crusted papules on the extensor surfaces of her bilateral arms. Punch biopsy findings are presented in the image above. Grocott methenamine silver and Ziehl-Neelsen stains are negative. Which of the following is the best diagnosis?
- Acute febrile neutrophilic dermatosis (Sweet syndrome)
- Erythema elevatum diutinum
- Granuloma annulare
- Reactive granulomatous dermatitis
- Rheumatoid nodule
Board review style answer #1
Board review style question #2
A 42 year old woman with poorly controlled rheumatoid arthritis presents with pink-brown, indurated, cord-like plaques on her trunk and flanks. A punch biopsy is performed and is shown above. Which of the following histopathologic features is characteristic of this entity?
- Degenerated collagen and fibrin surrounded by palisading histiocytes in the subcutaneous fat
- Degenerated collagen surrounded by palisades of histiocytes and neutrophils in the superficial to mid dermis
- Foci of degenerated collagen with dense mucin deposition surrounded by palisades of histiocytes
- Naked granulomas with Langhans type giant cells and asteroid bodies
- Papillary dermal edema with dense neutrophilic infiltrate and karyorrhexis
Board review style answer #2
B. Degenerated collagen surrounded by palisades of histiocytes and neutrophils in the superficial to mid dermis
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Reference: Reactive granulomatous dermatitis
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Reference: Reactive granulomatous dermatitis
