dermatology in general medicine

1. Cutaneous Drug Reactions
Introduction :
•Most frequent adverse reactions to drugs
•Presentation mainly focuses on the incidence, patterns, pathogenesis,
management and prognosis.
Incidence :
•3% of hospital in-patients.
•Reaction usually occurs a few days to 4 weeks after initiation.
•Most common is morbilliform rash ( 91%) and urticaria (6%)
•Severe reactions are too rare.

2. Cutaneous Drug Reactions
Pathogenesis :
•Most reactions are immunological in origin.
•Possibly drug acts as a hapten and binds to proteins.
•The structure formed is recognized as “non self”.
•Most are immune mediated hypresensitivity reactions, classified as
•Immediate reactions.
•Immune complex-dependent reactions.
•Delayed hypersensitivity reactions.
•Non immunologic mechanisms
•Pigmentary changes related to accumulation in dermis of
amiodarone, anti-malarials, minocycline, quinolones.
•Alteration of hair follicles by antimetabolites.
•Lipodystrophy associated with metabolic effects.

3. Cutaneous Drug Reactions
Pathogenesis : Immune mediated
Type I : IgE mediated, menifests as urticaria, angio-oedema and anaphylaxis.
Often caused by proteins and especially insulin.
Type II: Cytotoxic reaction produces haemolysis and purpura. Caused by
penicillin, cephalosporins, sulfonamides and rifampin.
Type III: is immune complex reactions, result in vasculitis, serum sickness
and urticaria. Caused by salicylates, chlorpromazine and sulfonamides.
Type IV: Delayed-type reactions, cell-mediated hypersensitivity, result in contact
dermatitis, exanthematous reactions and photoallergic reactions. Mostcommon, It is
not dose-dependent. Begin usually one to three weeks after medication is started.
There may be eosinophilia and may recur if chemically related drugs are used.
Immediate reactions include Type I and Type II.

4. Cutaneous Drug Reactions
Non immunologic
Warfarin induced necrosis of skin.
➢Rare devastating effect of warfarin therapy, consequence of occlusive
thrombi in vessels of the skin and subcutaneous tissue, and typically
begins three to five days after therapy is initiated.
➢Red, painful plaques evolve to necrosis with hemorrhagic blisters or
necrotic scars, frequently in areas with large quantities of adipose tissue,
including the breasts, hips, and buttocks.
➢Development unrelated to drug dose, and course not altered by
discontinuation.
➢Protein C deficiency causing hypercoagulability and thrombosis folled
by necrosis.
➢Treatment : Vit K, Heparin, and intensive wound care.

5. Cutaneous Drug Reactions
Warfarin induced necrosis of skin.

6. Cutaneous Drug Reactions
Non immunologic : Others
➢Exacerbation or induction of dermatologic disease.
➢Photosensitivity eruptions.
➢Pigmentation changes.
➢Drug induced hair disorders
•Drug induced hair loss
•Hirsutism.
•Hypertrichosis.
➢Drug induced nail disorders
•Onycholysis
•Onychomadesis
•Paronychia
•Nail discoloration.
➢Pruritus.

7. Cutaneous Drug Reactions
Immune Cutaneous Reactions : Benign
Maculopapular eruptions (Morbilliform)
•Most common of all.
•Distribution : starts onTrunk and Intertriginous areas.
•Erythematous macules and papules, frequently symmetric and may become confluent.
•Mucous membrane is seldom involved.
•Moderate to severe Pruritus and fever.
•Lab tests and Skin biopsy : Inconsclusive.
•Differentials :
•Viral exenthems
•Absence of enanthems, absence of ENT and URT symptoms, and Polymorphism of
skin lesions, supports Drug eruptions.
•Develop usually within 1 week of initiation and last less than 2 weeks.
•Management : Oral Anti-histaminics, emollients, and soothing baths.
In severe cases topical steroids can be used, systemic steroids ralely indicated.

8. Cutaneous Drug Reactions
Immune Cutaneous Reactions : Benign
Morbilliform Eruptions.

9. Cutaneous Drug Reactions
Urticaria / Angioedema
•Second most frequent.
•Characterized by pruritic red wheals of varying size.
•Single lesion rarely lasts more than 24 hours.
•Angioedema is deep dermal and subcutaneous edema, may involve respiratory and GI
mucous membranes.
•Severe form : Anaphylactic reaction.
•Mechanism : Three.
➢IgE-dependent mechanism, Immune-Complex dependent and non immunologic
activation of effector pathways.
•IgE dependent reactions usually occurs within 36 hours, but can occur within minutes.
•Immune-Complex reactions occur 6-12 days after exposure.
•There may be fever, hematuria, arthralgias, hepatic and neurologic symptoms.
•Causes : most common are ACEi, NSAIDs, penicillin, and Blood Products, but can
occur with any drug.
•Management : depends on severity, Severe cases with cardio-respiratory involvement
need Epinephrine, IV glucocorticoids. Inpatients with only cutaneous symptoms drug
withdrawal, and antihistamines are sufficient.

10. Cutaneous Drug Reactions
Fixed Drug Eruptions
•One or more sharply demarcated, erythematous lesions leading to blister
formation.
•Hyperpigmentation after resolution usually.
•With re-challenge, lesions reappear in the same (fixed) location, hence
Fixed Drug Eruptions.
•Involve Lips, Hands, Legs, Face, Genitalia, & oral mucosa is common,
cause burning sensation
•FDE are associated with Psedudoephedrine, phenolphthalin,
sulfonamides, TC’s, NSAIDs, and Barbiturates.
•Patch testing is helpful in making dioagnosis.

11. Cutaneous Drug Reactions
Fixed Drug Eruptions

12. Cutaneous Drug Reactions
Severe Cutaneous Reactions :
Pustular Eruptions
•Acute generalised exanthematous pustulosis (AGEP) : acute onset
fever, generalised scarlatiniform erythema, small, sterile, non-follicular
pustules.
•Skin biopsy needed to differentiate it from TEN.
• 7 - 14 days after administration.
•Other Causes : viral infections, mercury exposure, or UV radiation.
•Resolve spontaneously and rapidly, with fever and pustules lasting 7-10
days before desquamation.
•Typical Offenders : β-lactam antibiotics, macrolides and less commonly,
a wide variety of drugs including paracetamol, carbamazepine,
tetracyclines, diltiazem, furosemide, hydrochlorothiazide,
hydroxychloroquine, nifedipine, phenytoin, pseudoephedrine, ranitidine,
sertraline, simvastatin, terbinafine & vancomycin.

13. Cutaneous Drug Reactions
Severe Cutaneous Reactions :
Vasculitis
•Often present as palpable purpuric lesions, limited to
lower extremities or other dependent areas.
•May involve other organs.
•Infections, Malignancy, Collagen Vascular diseases
are non drug related causes of Vasculitis.
•Drugs : Propylthiouracil, Allopurinol, Thiazides,
Sulfonamides, and NSAIDs and other antimicrobials.

14. Cutaneous Drug Reactions
Severe Cutaneous Reactions :
Vasculitis

15. Cutaneous Drug Reactions
Hypersensitivity syndromes.
•a.k.a DRESS (Drug reaction with eosinophlia and
systemic symptoms) and DISH ( Drug induced
hypersensitivity syndrome).
•Rash in DHS occurs 2 to 8 weeks after drug
administration, starts later stays longer than most other
serious skin reactions.
•Initially presents with a morbilliform eruption,
indistinguishable from less serious reactions and
eventually develop into erythematous follicular
papules, pustules, bullae, or purpura.

16. Cutaneous Drug Reactions
Hypersensitivity syndromes.
•Fever, facial and periorbital edema, tender LAP
(75%), Leukocytosis, hepatitis(51%), and sometimes
nephritis(11%), and pneumonitis.
•Drugs : Phenytoin, Carbamazepine, lamotrigine,
minocycline, dapsone, allopurinol and sulfonamide,
abacavir, and zalcitabine.
•Cross-hypersensitivity common, and can occur
between aromatic anticonvulsants (i.e. phenytoin,
carbamazepine and phenobarbitone) as well as
NSAIDs.

17. Cutaneous Drug Reactions
Hypersensitivity syndromes.
Management
➢Treatment consists of immediate withdrawal of all suspected
medicines, followed by supportive care of symptoms.
➢Systemic corticosteroids are generally used in more severe
DHS cases involving significant dermatitis, pneumonitis
and/or hepatitis.
➢Prednisolone 1.5 – 2 mg/kg/day started with slow taper off
over 8 - 12 weeks.
➢Relapses may occur as corticosteroid doses are tapered, and
treatment may need to be continued for several weeks.

18. Cutaneous Drug Reactions
Stevens-Johnson Syndrome
➢Widely distributed purpuric macules and blisters and
prominent involvement of the trunk and face are likely to have
Stevens-Johnson syndrome, which is usually drug-induced
➢Generalized eruption of lesions that initially had a target-like
appearance but then became confluent, brightly erythematous,
and bullous.
➢Drugs implicated : Sulfonamides, nevirapine, allopurinol,
lamotrigine, aromatic anticonvulsants, and oxicam NSAIDs.

19. Cutaneous Drug Reactions
Stevens-Johnson Syndrome

20. Cutaneous Drug Reactions
SJS vs TEN
➢Limited areas of epidermal detachment are usually labeled
Stevens-Johnson syndrome and those with extensive
detachment toxic epidermal necrolysis.
➢Stevens-Johnson syndrome is characterized by sloughing of
less than 10 % of the epidermis
➢Toxic Epidermal Necrolysis is characterized by sloughing of
more than 30 % of the epidermis
➢About 90 percent of patients with each disorder have mucosal
lesions, including painful erosions and crusts on any surface.

21. Cutaneous Drug Reactions
SJS / TEN Management.
➢At present no treatment of proven efficacy
➢Early diagnosis, immediate withdrawl of offending
drug, supportive therapy, treating occular
complications and infections.
➢Systemic steroids ( Prednisolone 1-2 mg/kg) may be
useful early in evolution, but long term use is
associated with higher mortality
➢IVIG unlikely to benefit.

22. Cutaneous Drug Reactions
Prognosis
➢Most cases resolve without complications but it may
take 10 to 14 days for the rash to disappear.
➢Patients with exanthematous eruptions will have mild
desquamation as the rash resolves.
➢The Stevens Johnson syndrome has a mortality of
around 10% whilst toxic epidermal necrolysis carries a
mortality of 50%.*
* Mockenhaupt M; The current understanding of Stevens-Johnson syndrome and toxic epidermal
necrolysis. Expert Rev Clin Immunol. 2011 Nov;7(6):803-13; quiz 814-5.

23. Cutaneous Drug Reactions
Evaluation and management : Algorithm.

24. Cutaneous Drug Reactions
Evaluation & management: Algorithm.(contd..)

25. Cutaneous Drug Reactions
Take Home Message
➢Drug reactions are iatrogenic and hence contravene the principle
of primum non nocere - 'first do no harm'.
➢History is very important, like use of OTC drugs 'alternative' and illicit
medication etc.
➢Most drug reactions are minor and self-limiting.
➢Certain red flags must be noted:
•If the patient is systemically unwell, this is serious.
•If the rash is extensive, it could progress to a serious exfoliative
dermatitis.
•Detachment of the skin is serious.
•Involvement of mucous membranes including eyes and genitalia may
suggest Stevens-Johnson syndrome.
➢Recommendations for future use of drug.