Drugs leading to
eruption include calcium channel blockers, beta-blockers,
antidepressants, antihistamine & 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 :
There is evidence of vasculitis or vasculopathy.
(ii)
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.
The interstitial granulomatous drug reaction: a
distinctive clinical and pathological entity.
J Cutan
Pathol. 1998 Feb;25(2):72-8.
We present 20
patients in whom drug therapy was associated with interstitial
histiocytic infiltrates with variable degeneration of collagen and
elastic fibers mimicking early lesions of granuloma annulare (GA).
Most patients had a reproducible clinical presentation comprising
erythematous-to-violaceous, nonpruritic plaques, often with an
annular pattern, predominantly involving inner aspects of the arms,
medial thighs and intertriginous areas. The most frequent clinical
differential diagnoses included cutaneous T cell lymphoma, erythema
annulare centrifigum (EAC), GA, and lupus erythematosus. A drug
reaction was suspected in only 3 cases. The implicated drug classes
included calcium channel blockers, angiotensin converting enzyme
inhibitors, beta-blockers, lipid-lowering agents, antihistamines,
anticonvulsants and antidepressants. Patients were often on two or
more of these drugs; all have been associated with
pseudolymphomatous infiltrates of the skin, the presumptive basis of
which is iatrogenic pertubation of immune function. The defining
histomorphology was diffuse infiltration of the interstitium by
lymphocytes and histiocytes with piecemeal fragmentation of collagen
and elastic fibers in concert with a vacuolar interface dermatitis.
Ten cases showed intermediate and transformed lymphocytes with
hyperchromatic convoluted nuclei disposed interstitially within the
dermis or along the dermoepiderma junction with variable
epidermotropism. In the 15 patients who discontinued the implicated
drug, lesional resolution occurred. We propose the designations
interstitial granulomatous drug reaction for this novel cutaneous
reaction pattern.
Interstitial
granulomatous drug reaction with a histological pattern of
interstitial granulomatous dermatitis.Am
J Dermatopathol. 2001 Aug;23(4):295-8.
The
interstitial granulomatous drug reaction (IGDR) is a novel
drug-associated entity, characterized by violaceous plaques with a
predilection for skin fold areas. Light microscopically, it
resembles the incipient diffuse interstitial phase of granuloma
annulare. Differentiating light microscopic features include the
absence of complete collagen necrobiosis, the presence of interface
dermatitis, and variable lymphoid atypia. The lack of vasculitis
rules out the extravascular necrotizing granuloma (Winkelmann
granuloma) associated with systemic disease. The differential
diagnosis with interstitial granulomatous dermatitis with arthritis
as defined by Ackerman et al. has not been studied until now. Our
aim was to determine the histologic criteria allowing us to
differentiate IGDR without interface dermatitis and lymphoid atypia
from interstitial granulomatous dermatitis. We report three patients
with IGDR triggered, in two cases by respectively angiotensin
convertin enzyme (ACE) inhibitors and furosemide, and in one case by
the association of an ACE inhibitor, furosemide, and fluindione.
Histologic examination showed a histological pattern of interstitial
granulomatous dermatitis. We found a dense, diffuse histiocytic
infiltrate distributed interstitially and in palisaded array within
the reticular dermis. Eosinophils and some neutrophils were
scattered throughout the infiltrate. In some tiny foci, enveloped by
histiocytes, thick collagen bundles associated with basophilic
nuclear debris or "flame figures" were seen. Vasculitis, interface
dermatitis, or lymphoid atypia were absent. Our study allowed us to
expand the histological spectrum of IGDR including a histological
pattern similar to interstitial granulomatous dermatitis. The lack
of degenerated collagen could be a subtle clue in favor of
interstitial granulomatous dermatitis triggered by a drug.
