Drug Eruption and Interactions - PHARMACEUTICAL REVIEW

650 DESCRIPTION OF THE 34 MOST COMMON REACTION PATTERNS
Pseudoporphyria
Pseudoporphyria is an uncommon, reversible, photoinduced,
cutaneous bullous disorder with clinical, histologic
and immunofluorescent similarities to porphyria cutanea
tarda but without the accompanying biochemical porphyrin
abnormalities. It is commonly seen as localized bullae and
skin fragility on sun-exposed skin, often on the dorsum of the
hands and fingers. While pseudoporphyria has been linked
with numerous causes, including chronic renal failure, dialysis,
and ultraviolet radiation, several medications, primarily
naproxen and other nonsteroidal inflammatory drugs, have
been reported to trigger this reaction pattern. Blue/gray eye
color appears to be an independent risk factor for the development
of pseudoporphyria.
Psoriasis
Many drugs, as a result of their pharmacological action, have
been implicated in the precipitation or exacerbation of psoriasis
or psoriasiform eruptions.
Psoriasis is a common, chronic, papulosquamous disorder
of unknown etiology with characteristic histopathological
features and many biochemical, physiological, and immunological
abnormalities.
Drugs that can precipitate psoriasis are, among others,
beta-blockers and lithium. Drugs that are reported to aggravate
psoriasis are antimalarials, beta-blockers, lithium,
NSAIDs, quinidine, and photosensitizing drugs. The effect
and extent of these drug-induced psoriatic eruptions are
dose-dependent.
Purpura
Purpura, a result of hemorrhage into the skin, can be divided
into thrombocytopenic purpura and non-thrombocytopenic
purpura (vascular purpura). Both thrombocytopenic and
vascular purpura may be due to drugs, and most of the drugs
producing purpura may do so by giving rise to vascular damage
and thrombocytopenia. In both types of purpura, allergic
or toxic (nonallergic) mechanisms may be involved.
Some drugs combine with platelets to form an antigen,
stimulating formation of antibody to the platelet–drug combination.
Thus, the drug appears to act as a hapten; subsequent
antigen–antibody reaction causes platelet destruction
leading to thrombocytopenia.
The purpuric lesions are usually more marked over the
lower portions of the body, notably the legs and dorsal
aspects of the feet in ambulatory patients.
Other drug-induced cutaneous reactions – erythema
multiforme, erythema nodosum, fixed eruption, necrotizing
vasculitis, and others – can have a prominent purpuric component.
A whole host of drugs can give rise to purpura, the most
common being: NSAIDs, thiazide diuretics, phenothiazines,
cytostatics, gold, penicillamine, hydantoins, thiouracils, and
sulfonamides.
Raynaud’s phenomenon
Raynaud’s phenomenon is the paroxysmal, cold-induced
constriction of small arteries and arterioles of the fingers
and, less often, the toes.
Occurring more frequently in women, Raynaud’s phenomenon
is characterized by blanching, pallor, and cyanosis.
In severe cases, secondary changes may occur: thinning and
ridging of the nails, telangiectases of the nail folds, and, in the
later stages, sclerosis and atrophy of the digits.
Rhabdomyolysis
Rhabdomyolysis is the breakdown of muscle fibers, the
result of skeletal muscle injury, that leads to the release of
potentially toxic intracellular contents into the plasma. The
causes are diverse: muscle trauma from vigorous exercise,
electrolyte imbalance, extensive thermal burns, crush injuries,
infections, various toxins and drugs, and a host of other
factors.
Rhabdomyolysis can result from direct muscle injury by
myotoxic drugs such as cocaine, heroin and alcohol. About
10 to 40 percent of patients with rhabdomyolysis develop
acute renal failure.
The classic triad of symptoms of rhabdomyolysis is muscle
pain, weakness and dark urine. Most frequently, the involved
muscle groups are those of the back and lower calves. The
primary diagnostic indicator of this syndrome is significantly
elevated serum creatine phosphokinase.
Some of the drugs that have been reported to cause
rhabdomyolysis are salicylates, amphotericin, quinine, statin
drugs, SSRIs, theophylline, amphetamines, and others.
Toxic epidermal necrolysis (TEN)
Also known as Lyell’s syndrome, toxic epidermal necrolysis
is a rare, serious, acute exfoliative, bullous eruption of the
skin and mucous membranes that usually develops as a reaction
to diverse drugs. TEN can also be a result of a bacterial
or viral infection and can develop after radiation therapy or
vaccinations.
In the drug-induced form of TEN, a morbilliform eruption
accompanied by large red, tender areas of the skin will
develop shortly after the drug has been administered. This
progresses rapidly to blistering, and a widespread exfoliation
of the epidermis develops dramatically over a very short
period accompanied by high fever. The hairy parts of the
body are usually spared. The mucous membranes and eyes
are often involved.
The clinical picture resembles an extensive seconddegree
burn; the patient is acutely ill. Fatigue, vomiting, diarrhea
and angina are prodromal symptoms. In a few hours the
condition becomes grave.
TEN is a medical emergency and unless the offending
agent is discontinued immediately, the outcome may be fatal
in the course of a few days.