Rash following a drug taking

The onset of a rash following a drug taking is often related to the drug. This is called a drug eruption.

More rarely, in the case of viruses, it may be the natural history of the infection. Drug intake can have either then play no role in the onset of the rash (coincidence) or either trigger the eruption of a poorly understood immunological mechanism (the case of the eruption under ampicillin cases of infectious mononucleosis). In the latter case, there is no reason to consider that this is a drug eruption.Subsequent dosing is not against-indicated, once cured the current infection.

Drug eruptions are skin reactions medication data internally. The routes of administration can be oral (enteral), intravenous, subcutaneous or intramuscular injection.

It affects the skin and sometimes mucous membranes.

They are polymorphic in their clinical expression and severity. Diagnosis is usually a set of arguments, questioning with the chronology of the various drug intake is fundamental.

A small number of situations (Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption) directed primarily towards drug cause.

Skin lesions are not specific in the majority of cases.

They are usually benign, healing with stopping the drug.

The frequency of drug reactions is higher in women and in the elderly.

The most common drugs involved are antibiotics and anticonvulsants (Table I).

Recall the role of pharmacovigilance and legal obligation of all healthcare professionals to report any serious drug or unexpected effects of a drug.

The main drug reactions are described according to their clinical appearance.

Skin lesions are described, the elementary lesion (macula, papule, vesicle, bubble) specified.

Photographs (digital interest) may be made. Achieving mucosa should be clarified, and the affected skin surface.

Severity of the signs (Table II) are sought.

The presence of these signs and the land on which the drug eruption occurs (condition, comorbidities, social isolation) lead to hospitalization.

Laboratory tests are not standardized. More often than we realize an NFS looking for eosinophilia or lymphocytosis, creatinine to detect a possible kidney failure, blood electrolytes in case of suspicion of fluid and electrolyte disorders including dehydration, and liver function tests.

MACULOPAPULAR RASH:

This is the most common drug reaction. It occurs between the 4th and the 14th day after the start of drug intake (peak 9th day).

The rash may occur earlier in case of prior sensitization.

The rash starts on the trunk, the roots of the limbs, elbows and knees and spreads.

There is a polymorphism of the lesions Isolated macules, a morbilliform aspect webs scarlatiniform places as well as the possibility of oedematous papules or plaques, as well as a petechial purpura on the legs.

Itching is usually moderate.

General symptoms, if present, are discreet fever usually mild or absent, asthenia, pruritus. Eosinophilia is inconstant.

The evolution is usually favorable in a week after stopping the drug. Post-inflammatory desquamation may occur.

There is no mucosal involvement, skin detachment (Nikolsky’s sign), bubble, edema of the face, high fever, lymphadenopathy, purpura or necrosis. The deterioration of general condition, extensive skin lesions, severity of functional symptoms (itching, skin burns) are also warning signs. These signs, if present, have to fear the onset of a more serious drug eruption (eg, toxic epidermal necrolysis, drug hypersensitivity syndrome …)

The diagnosis is clinical, based on the timing of onset compared to drug intake, clinical appearance of the rash.

The main differential diagnosis is a rash occurring during viral infection (see erythema). It is more common in children than in adults, there is no polymorphism lesions, enanthema, there is a concept of contagion and flu-like symptoms. Erythema staphylococcal and streptococcal are away (cf. erythema).

Biopsy for histological analysis is mostly useless.

The drugs involved are frequently aminopenicillin, sulfonamides, TB, the antiepileptic, captopril, NSAIDs and former gold salts.

Treatment is based on stopping the drug due to the extent possible. Symptomatic measures are essential: antihistamine such Clarytine® 1 tab / day or 25 mg Atarax® night for discomfort to sleep, application of emollients or topical corticosteroids in decreasing doses.

DIAPER PIGMENTED FIXED:

This is a particular drug eruption by its clinical appearance that is almost pathognomonic.

It occurs within 48 hours after drug intake.

It begins with itching and localized burns.

It then appears one to ten roughly rounded erythematous plaques, although limited, indurated and painful. They are sometimes bullous or vesicular. They can affect the mucous membranes, in isolation or not: external genitalia, lips.They are often balanced on the trunk and limbs. They can leave hyperpigmentation sequelae, allowing retrospective diagnosis.

The outcome was favorable in case of stopping treatment involved.

The lesions are fixed and tend to recur in the same place where new drug intake.

Stopping the drug is due much of the processing. This is often barbiturates, sulfonamides, carbamazepine or cyclins.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS:

The acute generalized exanthematous pustulosis occurs in the first four days (ten days) of drug taking. In subjects already aware, the period may be very short.

With fever, first appear erythematous closets, scarlatiniform, lupus. The folds and trunk (axillary, inguinal) are gladly initially affected.

These cupboards are rapidly developing small superficial pustules, milky nonfollicular, less than 5 mm in diameter.Oral or genital injury is possible. The fever is sometimes higher with chills.

These elements can be feared wrongly septic process, especially since it may be a neutrophilic leukocytosis.

Biopsy, if practiced, shows a pustule in cornea with accumulation of neutrophils in the superficial part of the epidermis, edema of the superficial dermis and leukocytoclastic vasculitis inconsistent.

The prognosis is usually favorable with spontaneous recovery in a fortnight. Complications, rare, can be hypoalbuminemia, hypocalcemia, renal functional impairment. Recall the infectious risk of an extended dermatitis.

On stopping the drug involved, the outcome was favorable in one to two weeks.

The drugs in question are antibiotics (beta-lactams, macrolides), calcium channel blockers (diltiazem), the quinidiques, tetracyclines, fluoroquinolones, Bactrim, synthetic antimalarials.

The differential diagnosis is mainly with besides an infectious process, the superficial pustular psoriasis. In its favor, there is a less abrupt onset, lower fever, a more prolonged course of life and history of psoriasis.

Treatment:

Treatment is based on stopping the drug due, local care (type of emollients Dexeryl® one application per day, local corticosteroid Diprosone® or Betneval®) and maintaining proper hydration.

URTICARIA AND ANGIO-EDEMA:

Urticaria:

The clinical appearance of drug-induced urticaria is comparable to ordinary urticaria. It occurs within minutes or a few hours after drug intake, or seventh day. In this case, it is often fixed, is accompanied by joint pain and is similar to serum sickness.

The beta-lactam antibiotics, insulin, muscle relaxants, bupropion (Zyban) can cause urticaria.

Treatment is based on antihistamines and drug eviction.

Angioedema:

The medicated angioedema is seen especially with penicillins, hyperosmolar iodinated contrast agents and angiotensin converting enzyme inhibitors. It can be with or without urticaria.

It requires immediate hospitalization, administration of corticosteroids (Solumedrol 80 mg) and antihistamines (Polaramine®, 1 bulb) parenterally emergency. In the most severe cases, epinephrine (0.5 mg subcutaneously) may be given (see Edema of the face).

Recall the need for the eviction of aspirin in patients intolerant to non-steroidal anti-inflammatory drugs, whether or not a triad of Widal.

Angioedema occurring as angiotensin converting enzyme inhibitors may recur in sartans.

Corticosteroids may cause a flush in the hours after taking.

PHOTOSENSITIVITY AND Photoallergy:

(See photosensitivity)

DRUG HYPERSENSITIVITY SYNDROME:

The drug hypersensitivity syndrome is a serious drug eruption preferentially occurring 2-6 weeks after the start of drug taking, so much later than other drug eruptions.

The drugs involved are especially anticonvulsants (carbamazepine, phenytoin, phenobarbital …), antibiotics (sulfonamides, trimethoprim-sulfamethoxazole, minocycline …), nonsteroidal anti-inflammatory drugs.

It may begin as a maculopapular rash but quickly noted an extension of the rash and edema particularly strong face.At the status stage, there is a high fever, superficial lymphadenopathy, hepatosplenomegaly and arthromyalgia.

The patient should be hospitalized because there is a risk of causing serious visceral (interstitial lung disease, kidney failure interstitial nephropathy, mixed hepatitis, myocarditis …)

Biologically, there eosinophilia, lymphocytosis with activated lymphocytes and possible mononucleosis and signs related to a possible organ involvement (renal failure, hepatic cytolysis …)

Mortality, probably overestimated by publication bias, would be 10%. It is due to visceral.

Evolution can be extended with possible relapse.

Black patients suffer from more severe DRESS.

Prior or concurrent viral infection is sometimes found (HHV6, HIV, EBV …)

The patient should be hospitalized. The suspects drugs must be stopped. The evolution is usually favorable.Treatment is symptomatic: application of topical steroids such Diprosone® in case of inflammatory lesions, antihistamines important pruritus, substitute according to organ dysfunction.

Systemic corticosteroids are usually avoided because it would promote relapse. Some suggest the administration of intravenous immunoglobulin in the most severe cases.

STEVENS-JOHNSON SYNDROME AND LYELL:

There is a spectrum of bullous diseases characterized by the same histological image, toxic epidermal necrolysis (necrosis of keratinocytes by apoptosis).

This is the most serious drug reactions. HIV subjects are most at risk.

Stevens-Johnson syndrome has a pluriorificielle predominant mucosal involvement with less than 10% skin involvement. Lyell’s syndrome has a top skin involvement at 30% of the body surface.

The drug eruption began about ten days to twenty days after the start of treatment, often by non-specific signs: fever, flu syndrome … She can mimic an ordinary seasonal infection. Then appear mucosal lesions: conjunctivitis, eye burns, oral erosions, nasal, genital, pharyngitis …

Rash is rapidly progressive and extensive, with dark red blotches, pseudo-rosettes, diffuse erythema and especially skin peeling exposing the bright red oozing dermis. The appearance is that of wet laundry.

Delamination can be caused by the surrounding skin pressure (Nikolsky’s sign).

Detachment zones are rather limited in Stevens-Johnson syndrome and greater in toxic epidermal necrolysis. The pseudococardes are more common in Stevens-Johnson syndrome. Then they predominate on the trunk.

The patient should be hospitalized urgently at best if toxic epidermal necrolysis in intensive care or dermatology.There may be fever, poor general condition, food difficulties and significant fluid and electrolyte disorders.

Of visceral involvement may occur: lung, liver, pancreas, digestive, and impaired glucose regulation.

Skin biopsy showed necrosis of the skin over the entire height of the mucous body.

Mortality is high, of the order of 20 to 30%. It is even larger than the drug eruption occurs on unfavorable ground: immunosuppressed, diabetics, renal failure …

Superinfection would be responsible for a large number of deaths.

The patient should be hospitalized urgently in dermatology or service specialized type of resuscitation or burn.

All drugs and those not attributable vitally needed to be decided.

Treatment is mainly symptomatic equilibration with solid electrolyte intake of electrolytes, enteral feeding, local nursing care, analgesics, insulin therapy, correction of any organ failure …

Some suggest treatment with intravenous immunoglobulin remains discussed. It is the same for corticosteroids.

The prognosis is good in most cases.

The risk of death is 20 to 30%. The rééperdimisation occurs within 10 to 30 days in case of favorable outcome. There is a risk of ocular sequelae (adhesions), pigmentary sequelae and nail dystrophies.

VASCULITIS HYPERSENSITIVITY:

The clinical appearance is that of a vascular purpura, infiltrated, predominating on the lower limbs.

There may be a polymorphism of the lesions with pseudo-urticarial lesions bubbles.

There are no thrombocytopenia. Signs of visceral involvement are discreet: polyarthralgias, abdominal pain … must be eliminated syste matically renal impairment (dipstick, creatinine and calculation of creatinine clearance, urine culture …)

Vasculitis occurs 1-10 days (maximum 21 days) after the drug intake. The re-entry of a drug for which the patient is already sensitized, it occurs in less than three days. When in doubt Diagnostic and if visceral involvement, the patient should be hospitalized. The attributable drugs should be stopped. This is most often allopurinol, furosemide, iodine, hydantoin, penicillins, sulphonamides and propio-thiouracil.

DELAYED HYPERSENSITIVITY REACTIONS TO THE INJECTION SITE HEPARINS:

They occur hours to days after the administration of heparin. The lesions at the injection site are eczematiform closets.

There may be itching and remote maculopapular lesions.

The cross-hypersensitivity between low molecular weight heparins and unfractionated. We must entrust the patient to the specialist to perform skin tests to determine which replacement therapy to the patient. We must apply a type of topical corticosteroid Diprosone® see Dermoval® the injection site and make an early relay AVK. Replacement products may be Orgaran® (heparinoid) or Arixtra (fondaparinux).

BABOUIN SYNDROME:

The drug eruption is a very limited perianal erythema and buttocks or groin areas and périgénitales V, symmetrical, with another fold achieved.

There is no systemic involvement.

It occurs a few hours to a few days after taking the drug responsible (mainly beta-lactams and amoxicillin).

The drug discontinuation and symptomatic treatment are sufficient.

OTHER REACTIONS:

Halogenides:

The administration of iodinated or brominated derivatives may result in additional closets or macaroons vegetating, dotted with scabs and oozing.

We call these lesions halogenides.

The folds are readily achieved. The lesions are usually chronic.

Specialist advice is required. The substances in question should be avoided.

Blood and urine levels of iodine and bromine, histology are suggestive.

Hemorrhagic necrosis:

They are secondary to the use of anticoagulants.

Vitamin K can induce hemorrhagic necrosis in early treatment following the fall of the rate of protein C or S

Then there are inflammatory plaques affecting mainly the thighs and abdomen. These plates become ecchymotic and secondarily necrotic.

Various:

There are rare drug reactions and remain in the field of specialty. Include drug pseudolymphomas the pseudoporphyries mimicking cutanea tarda, lichenoid drug eruptions …

Some drugs have also been attributed to the occurrence of various inflammatory skin diseases: systemic lupus erythematosus, pemphigus, dermatomyositis, scleroderma …

MANAGEMENT AND ACCOUNTABILITY:

Supports:

The concepts of care for each type of drug eruption have been detailed above.

Any suspicious or not vitally essential drug should be discontinued. This is imperative for serious drug eruption. In case of less serious drug eruption and life-threatening, the medication may be continued under hospital supervision.Symptomatic treatment should be started (anti-H1 antihistamines possibly corticosteroids). This is the case for example in cases of maculopapular rash under Bactrim® given for Pneumocystis about HIV. The occurrence of mucosal lesions or skin peeling will have to fear the occurrence of bullous drug eruption and stop the drug.

Symptomatic treatment is usually a combination of an anti-H1 antihistamine (eg Clarytine® 1 day; Atarax® 25-50 mg at night when sleeping) and an emollient (eg , Dexeryl® cream 1 tube 250 g).

Desensitization is helpful if true penicillin allergy after allergy testing has been made and be positive.

The support is then allergy

Accountability:

Remember that any health professional has the obligation to report to pharmacovigilance any serious or unexpected adverse events related to medication.

The diagnosis of drug eruption based on a body of evidence. Extrinsic accountability are distinguished (data from the literature and pharmacovigilance centers) and intrinsic (clinical history of the patient). It is based on chronological and semiological criteria.

The interview plays a key role in establishing the chronology and completeness of drug intake. Be careful not to omit certain medications forgotten by the patient (self-medication with non-steroidal anti-inflammatory counter example).The other pitfall is to report wrongly by excess drug eruptions to a drug.

The timing of drug intake facing the clinical aspect is a good orientation element (Table III).

A drug well tolerated earlier may be responsible (initial sensitization phase).

The delay is incompatible if the drug was taken after the beginning of the unrest.

The evolution after drug withdrawal is important.

The improvement after discontinuation of treatment, worsening if pursued are suggestive.

Evolution is called inconclusive if healing is achieved through an effective symptomatic treatment or if the change is unknown.

Reintroduction of the tests are dangerous and should not be performed.

Remember also the importance of the field: think first before a maculopapular rash to a viral infection in children and a drug eruption in adults, more frequent drug reactions in HIV + patients …

The analyzed semiological criteria are the type of accident, contributing factors, possible non-drug etiologies and additional examinations. She then made a decision table, sent to the reporting physician.

Chargeable against-drugs are indicated.

A certificate detailing drug eruption and medicines due to be delivered to the patient. Drug names must be indicated by their trade name and under the international name. The drugs of the same class should be avoided.

The patient will have to show the certificate to any health professional may provide a drug (eg, pharmacist or dentist …)

A similar letter should be sent to the patient’s referring physician.

It should prohibit self-medication. Eventually, it will also give him a list of drugs that can take in place of banned drugs: NSAIDs other class or corticosteroids in case of reaction to NSAIDs; paracetamol if fever …

Some propose to carry out six months after the start of drug eruption skin tests. This is still research. They are cons-indicated if the drug eruption in question was a DRESS, vasculitis, a Stevens-Johnson syndrome or toxic epidermal necrolysis.