Cutaneous Reactions to Drugs - An Insight

Introduction

Cutaneous adverse drug reactions (CADR), also called toxidermia, are skin conditions resulting from the administration of systemic drugs. These reactions vary from mild erythematous skin lesions to severe reactions like Lyell's syndrome. Most systemic drugs are possible causes of cutaneous adverse reactions, such as antibiotics, anticonvulsants, antineoplastic drugs, nonsteroidal anti-inflammatory drugs, and Allopurinol. In addition, antibiotics and anti-epileptics produce toxidermia.

What Are the Common Cutaneous Reactions to Drugs?

Some of the common drug reactions are mentioned below.

• Morbilliform or exanthematous drug eruption.

• Urticaria.

• Angioedema.

• Drug hypersensitivity syndrome.

• Stevens-Johnson syndrome.

• Serum sickness.

• Hypersensitivity vasculitis also called palpable purpura.

• Fixed drug eruption.

• Lichenoid drug eruption.

• Drug-induced photosensitivity.

• Bullous drug eruptions.

• Drug-induced lupus erythematosus.

• Drug-induced skin pigmentation.

• Systemic contact dermatitis.

• Allergic contact dermatitis.

• Photo contact dermatitis.

• Hair loss.

• Increase in hair.

• Nail dystrophy.

What Are Cutaneous Reactions to Drugs?

There are multiple factors for the variability in drug reactions. However, they can be classified into two broad categories: immunologic and nonimmunologic. The majority of adverse drug reactions are secondary to non-immunologic variants. At the same time, the residual unfavorable responses are immune-mediated. Therefore, the only cases of adverse drug reactions are immune-mediated reactions. Immune-mediated reactions most typically consist of either immediate or delayed immunologic responses. Consequently, it is essential to test for potential allergens to differentiate drug reaction causes. The most common testing methods include epicutaneous patch, prick, and intradermal testing. However, in vivo or in vitro tests cannot establish the drug's causality. Some of the cutaneous drug reactions are mentioned below.

• Bullous reactions.

• Stevens-Johnson syndrome.

• Toxic epidermal necrolysis was known as Lyell syndrome.

• Acute generalized exanthematous pustulosis (AGEP).

• Drug reactions with eosinophilia and systemic symptoms (DRESS).

What Are the Features of Cutaneous Drug Reactions?

Cutaneous drug reactions show various features. Some of the common features of cutaneous drug reactions are mentioned below.

• Exanthematous eruptions.

• Urticarial toxidermia.

• Fixed pigmented erythema (FPE).

• Toxic epidermal necrolysis or TENs.

• Drug reaction with eosinophilia and systemic symptoms (DRESS).

• Acute generalized exanthematous pustulosis (AGEP).

Exanthematous Eruptions:

• Also called morbilliform or ery­thematous maculopapular outbreaks,

• The most common type of drug reaction.

• The rash forms within one day to three weeks.

• Polymorphic maculopapular lesions are seen with no mucosal involvement, resembling features of viral exanthem are present.

• The primary involved site is the trunk or in areas of pressure and trauma. Next, they spread to affect the extremities; clinical features are symmetrical.

• Causative drugs include antibiotics like beta-lactams, sulfonamides, nonsteroidal anti-inflammatory drugs (NSAIDs),

• Antiepileptics such as Carbamazepine, Hydantoins, and Allopurinol.

Urticarial Toxidermia:

• Also called urticaria and Quincke's edema.

• Immediate urticaria occurs rapidly within one or two hours.

• Immediate drug discontinuation is due to the possibility of the consequence of anaphylaxis.

• Delayed urticaria usually occurs slowly, days after the administration of the drugs.

Fixed Pigmented Erythema (FPE):

• Fixed pigmented erythema (FPE), a fixed drug eruption, occurs a few days after administering the offending medication.

• Single or multiple rounds characterize the traditional form of oval-shaped macules, ranging from red to brown.

• These lesions might turn into plaques, vesicles, or blistering.

Toxic Epidermal Necrolysis, TENs:

• Toxic epidermal necrolysis (TEN), also known as Lyell syndrome and Stevens-Johnson syndrome (SJS), is the most severe form of toxidermia or cutaneous drug reactions.

• Symptoms start within a month after initiation of the causative medication.

• The clinical features may spread anywhere in the body.

• The skin lesions typically appear as a dark red or purpuric macular rash. The eruption usually starts on the face and then gradually spreads symmetrically to other body parts.

• A positive Nikolsky sign is observed.

• Other symptoms include high fever, rapid dehydration, and the superinfection of skin lesions.

• Tachypnea (characterized by a higher-than-normal respiratory rate, resulting in unusually quick and shallow breathing).

• Hypoxia (a situation in which the entire or a portion of the body lacks enough oxygen delivery at the tissue level).

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS):

• Also termed drug-induced hypersensitivity syndrome.

• Late-onset skin eruption, two to six weeks after initiation of the medication.

• The nonspecific eruption,

• Pruritic maculopapular exanthem or a febrile erythroderma are present. Infiltrated facial edema.

• Rarely can skin features like small bumps, purpura, or erythema multiforme lesions be seen.

• Commonly involved organs include the liver, kidney, lungs, heart, and pancreas.

• Eosinophilia and a mononucleosis-like syndrome are present.

• Affected people must be hospitalized and should be observed under regular follow-ups.

Acute Generalized Exanthematous Pustulosis (AGEP):

• Scarlatiniform erythematous rash.

• Bumps are small and predominantly present in the axillary and inguinal folds.

• The papules can coalesce.

• Cutaneous desquamation is present.

• Triggers of acute generalized exanthematous pustulosis (AGEP) are the antibiotics, most typically Aminopenicillins and Macrolides.

• Symptoms are acute.

• Burning and pruritus are present.

How to Diagnose Cutaneous Drug Reactions?

A careful history, physical examination, and skin are necessary to diagnose a drug reaction in the skin. The various other diagnostic tools for analyzing cutaneous drug reactions are mentioned below.

• History of the patient.

• Medical history, which includes the intake of antibiotics and anti-epileptic drugs.

• Blood tests include blood count.

• Liver function and kidney function tests.

It is sometimes difficult to determine which drug is responsible for a rash, if any. This is because very few drug reactions have a confirmatory test. An allergy specialist and immunologist can examine the skin. They may perform the following tests:

• Intradermal or prick tests.

• Patch tests.

What Is the Treatment for Drug Eruptions?

The initial mode of treatment includes the cessation of drugs causing adverse reactions and managing the symptoms. Some other treatment measures are mentioned below.

In severe cases, visit a nearby doctor or dermatologist immediately.

• Topical corticosteroids such as Betamethasone cream are effective and reduce symptoms.

• Emollients can be used.

• Antihistamines are helpful for drug-induced skin reactions and other eruptions.

• Educate the patient.

Conclusion

Cutaneous drug reactions are common and cause several skin problems. The symptoms of cutaneous drug reactions include pruritus, rash, edema, vesiculobullous lesions, and other phototoxic reactions. The skin features of cutaneous drug reactions look like allergic reactions, and the treatment is mainly based on the severity of the condition. Patch tests confirm the diagnosis, and treatment is done to manage the symptoms. Patient education regarding the effects of the drugs helps avoid complications.