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Pathology of Interstitial Granulomatous Drug Reaction

Dr Sampurna Roy MD           





Drugs leading to eruption include calcium channel blockers, beta-blockers, antidepressants, antihistamine and anticonvulsants.

Clinically the lesions present as erythematous to violaceous non-pruritic plaques often with an annular configuration.

Microscopic features:


The epidermis usually reveals an interface dermatitis (basilar vacuolopathy and focal dyskeratosis with lymphocytes present along the dermoepidermal junction).

In some cases, there is a lichenoid pattern of infiltration.

In the dermis there is a diffuse granulomatous dermatitis characterized by interstitial histiocytes, including giant cells .

These are present close to collagen and elastic fibers.

Tissue eosinophilia is present in most cases.

There may be piecemeal fragmentation of collagen and elastic fiber engulfment by giant cells together with variable interstitial mucin deposition.

Collagen necrobiosis with a palisading histiocytic infiltrate is rare.

Blood vessels are infiltrated by mononuclear cells.

There is usually no fibrin deposition and vasculitis.

Extravasated red blood cells may be present (must rule out pigmented purpuric dermatoses).

Lymphoid atypia is often identified.

The cell is characterized by mononuclear cells whose nuclei are hyperchromatic, small to medium-sized, with convoluted nuclear contours. 

In some cases there is a cerebriform morphology.

Differential Diagnosis:

(i) Granuloma Annulare and granuloma annulare-like tissue reactions in systemic disease :

- Absence of significant necrobiosis

- Predominance of lymphocytes over histiocytes

- Presence of eosinophils

- Interface change

There is evidence of vasculitis.

(ii)  Interstitial Granulomatous Dermatitis:  Deep dermis is not thickened and involved.

Rimming of collagen bundles by histiocytes is less prominent.

(iii)  Granulomatous cutaneous T-cell lymphoma and its variant, granulomatous slack skin :

The atypical cells in the interstitial granulomatous drug reaction are usually located in the dermis and are usually  not present within the epidermis.

In cutaneous T-cell lymphoma, the most atypical lymphocytes are usually seen within the epidermis.


Further reading:

Interstitial granulomatous drug reaction to adalimumab.

Interstitial granulomatous drug reaction to anakinra.

Interstitial granulomatous drug reaction presenting as erythroderma: remission after discontinuation of enalapril maleate.

Amoxicillin-Induced Eosinophilic Pneumonia with Granulomatous Reaction: Discrepancy between Drug-Induced Lymphocyte Stimulation Test Findings and the Provocation Drug Test.

A case of interstitial granulomatous drug reaction due to sennoside.

Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.

The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity.





Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)






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