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Dermpath-India

Drug Related Cutaneous Reaction

Dr Sampurna Roy MD            

 

                                                                                                                      

 

 

Drug reaction is defined as undesirable response caused by medicinal substance.

 

Histological features indicative of drug reaction:

1. Presence of eosinophils

2. Activated lymphocytes (larger in size)

3. Apoptotic keratinocytes

4. Presence of plasma cells in some cases.

5. Extravasation of red blood cells

6. Edema in some cases

7. Endothelial cells lining the blood vessels are swollen.
 

 

Drugs causing cutaneous reaction:

1. Antibiotics (Example. Co-trimoxazole, ampicillin, amoxycillin,  penicillin, sulphonamides etc).

2. Non-steroidal anti-inflammatory drugs

(Example. Aspirin, indomethacin, ibuprofen, phenylbutazone, mefenamic acid. 

3. Phenytoin sodium (anticonvulsant)

4. Psychotropic drugs (tricyclic antidepressants, lithium, tranquilizers)  

5. Anticancer chemotherapeutic drugs

(Example. Fluorouracil, doxorubicin, methotrexate etc)

6. Gold

7. Thiazide diuretics

8. Antimalarial drugs

9. Beta- blockers

10.Recombinant cytokines

11. Retinoids

 
Drug Related Clinicopathological Patterns:


1.   Exanthematous Drug 

2.   Halogenoderma

3.   Urticaria

4.   Photosensitive Reaction

5.   Toxic Epidermal Necrolysis

6.   Lichenoid / Interface pattern  

- Lichenoid Drug Reaction

- Fixed drug reaction    

- Erythema Multiforme 

- Lupus erythematous - Like Reaction 

7.  Vesiculobullous and pustular reaction   

8.  Spongiform reaction   

9.  Granulomas

10. Vasculitis   

11. Psoriasiform  Drug  Reactions

12. Acne  

13. Panniculitis

14. Erythema Nodosum    

15. Exfoliative Dermatitis (Erythroderma)

16. Hypersitivity Syndrome

17. Pigmentation

18. Pseudolymphoma

19. Lipodystrophy

20. Elastosis Perforans Serpinginosa 

 

Drug related reactions patterns:

1. Exanthematous drug reaction:

Drugs associated with this reaction include Ampicillin, amoxyllin, allopurinol, co-trimoxazole, penicillin, erythromycin, streptomycin, tetracyclin etc. 

Reaction develops on the first day or within 3 weeks.

Morphological  features:

Erythematous papules and macules. 

First appears on the trunk or on areas of trauma or pressure and later spreads to the extremities.

Microscopic features:  

Small foci of spongiosis, vacuolar degeneration in the basal layer, apoptotic keratinocytes.

Activated lymphocytes, some eosinophils and plasma cells  in the papillary dermis. 

2. Halogenoderma (iododerma, bromoderma, fluroderma):

Caused by ingestion of iodides, bromides  and fluorides.

Clinically, lesions may occur on face, neck , back or extremities as papules, pustules or vegetating nodules.

Microscopic features: Pseudoepitheliomatous hyperplasia of the epidermis, intraepidermal abscesses and in some cases dermal abscesses.

Differential diagnosis: Chromomycosis and sporotrichosis.

3. Urticaria:

Acute urticaria in infants may be  caused by furazolidone used in the treatment of diarrhea.

Chronic urticaria may be aggravated by salicylates.

Cold urticaria may follow use of penicillin  and griseofulvin.

Clinically, urticaria is characterized by transient pruritic, edematous, erythematous papules with central clearing.

Microscopic features: There is mild, perivascular inflammatory infiltrate (mostly lymphocytes, sometimes eosinophils and mast cells) and dermal edema.

In early case intravascular and perivascular neutrophils may be noted.

In coexisting angioedema there is edema of subcutaneous tissue and mucous  membrane.

4. Drug induced lichenoid / interface patterns:

- A: Lichenoid drug eruption

- B: Fixed drug eruption

- C: Erythema multiforme

- D: Lupus erythematosus

A. Lichenoid drug eruption:

Drugs : Beta-adrenergic blockers, methyldopa, antimalarial drugs,  penicillamine etc.

Clinically the lesions mimick lichen planus.

Postinflammatory pigmentation is more prominent than LP.

Microscopic features: Focal parakeratosis.

Mild basal vacuolar change.

Few eosinophils and sometimes plasma cells are present.

Less dense and less band like inflammatory infiltrate.

More pigment incontinence.

Differential diagnosis: Lichen planus.

B. Fixed drug eruption:

Drugs: Sulphonamides, Co-trimoxazole, tetracyline, tranquilizer, quinine and others.

Clinically round or oval erythematous lesion.

Microscopic features: Prominent vacuolar change.

Civatte body formation at and above the level of basal layer.

Inflammation obliterate dermoepidermal junction.

The inflammatory cells in drug eruption extends to mid and upper epidermis. Few neutrophils are present.

Differential diagnosis: Erythema multiforme.

C. Erythema multiforme:

Drugs: Sulfonamides, non-steroidal anti-inflammatory drugs and numerous other drugs.

Microscopic features: Divided into  epidermal, dermal or mixed types depending on the histological features.

Interphase reaction pattern.

Mild to moderate inflammatory infiltrate at the dermoepidermal junction.

Apopotic body at and above the basal layer.

Subepidermal cleft formation in the vesicular lesions.  

D. Lupus erythematosus:

Subacute:  Drugs: Thiazide, antihistamine, calcium channel blocker, griseofulvin, terbinafine etc.

Systemic: 

Drugs: Procainamide, isoniazid, sulphonamide, quinidine, penicillamine, phenylbutazone and many others.

Microscopic features:

Features of interphase dermatitis.

Superficial & deep dermal infiltrate.

Basal vacuolar change and occasional  Civatte bodies.

Epidermal atrophy, dermal edema, superficial mucin, basement membrane thickening.

Follicular plugging. 

Eosinophils may be present in drug induced cases. 

5. Toxic epidermal necrolysis:      

Severe form of Erythema multiforme.

Clinically, presents as generalized erythema which progresses to blistering lesions with peeling of skin.

Classification based on epidermal detachment:

Steven-Johnson Syndrome- Less than 10% of body surface.   

Steven-Johnson Syndrome/ toxic epidermal necrolysis.

Between 10% - 30% of body surface.

Toxic epidermal necrolysis - More than 30%.

Drugs implicated:  Sulphonamide, anticonvulsants, non-steroidal anti-inflammatory drugs, allopurinol, rantidine etc.

Microscopic features:

Subepidermal bulla.

Necrosis of epidermis.

Satellite cell necrosis. 

Perivascular lymphocytic infiltrate.

Necrosis of sweat ducts.

6. Drug related vesiculobullous and pustular reactions:

- Subcorneal pustular dermatosis: Cephalosporin etc.

- Acute generalized exanthematous  pustulosis: Paracetamol, antimalarial, amoxicillin.

- Pemphigus vulgaris and vegetans: Ampicillin

- Pemphigus foliaceus and erythematous: Aspirin etc.

- Subepidermal bulla :

Cell poor -  Pseudoporphyria- Sulphonamide

Eosinophils - Bullous pemphigoid- Ampicillin etc.

Neutrophils - Linear IgA bullous dermatosis- Frusemide

Scarring -  Cicatricial pemphigoid-  Azathioprine etc

Necrosis -  Drug overdose related- morphine, barbiturate

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

 

                                                                                                                                            


 

 

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