Page 1815 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1284 PART 11: Special Problems in Critical Care

occurs at the site of contact, which, with time, may become lichenified TABLE 129-5 Chemotherapy-Induced Dermatoses
(thickened with accentuation of skin markings) related to rubbing or
scratching. Type of Reaction Responsible Drugs Treatment
Diagnostic tests for CADR may be useful to determine the causative Alopecia (anagen or Vincristine, cyclophosphamide, • None
agent, the type of reaction, and the prognosis. Skin testing may be telogen effluvium) doxorubicin, daunorubicin,
performed by a prick or intradermal administration of the suspected dactinomycin, paclitaxel
drugs to determine the presence of drug-specific IgE antibodies (type I
Gell-Coombs reactions). Penicillin, muscle relaxants, and barbiturates Mucositis/stomatitis Topotecan, methotrexate, • Oral hygiene
are amenable to this type of testing because their epitopes are known. fluorouracil, doxorubicin, • Magnesium/aluminum
Medicines that undergo significant metabolism and those with unde- dactinomycin, bleomycin, hydroxide
fined epitopes cannot be tested. An in vitro test to study the presence docetaxel, daunorubicin • Viscous lidocaine
of circulating drug-specific IgE antibodies is the radioallergosorbent • Benzocaine
test. Penicillin, insulin, thiopental, protamine, latex, chymopapain, and • Diphenhydramine elixir
selected muscle relaxants can be tested by radioallergosorbent test, with Candidiasis Vincristine, cisplatin, • Nystatin wash/cream
variable consistency. doxorubicin, daunorubicin
When ADRs are mediated by drug-specific T cells (type IV; eg, contact Extravasation reactions Bleomycin, carboplatin, • Discontinue infusion
dermatitis), patch testing is a useful adjunct. It is performed by applying cyclophosphamide, doxorubicin, • Elevate effected extremity
predetermined dilutions of the compound on intact skin for different etoposide, paclitaxel, • Apply local heat or cold
periods and assessing for erythema, edema, or vesiculation, all indicative vinblastine • Debridement/skin grafting
of specific T-cell reactivity. A skin biopsy aids in clarifying the patho- • Use antidotes
physiology of a reaction, for example, by the demonstration of immune a b
complexes, leukocytoclastic vasculitis, or tissue eosinophilia. Blood Hyperpigmentation Bleomycin, cisplatin, • None
(localized or diffuse)
methotrexate, cyclophospha-
c
eosinophil counts have been regarded as an indicator of ADR; however,
recent studies have shown that this criterion carries a low sensitiv- mide, daunorubicin, doxorubicin
fluorouracil, hydroxyurea,
ity (22%-36%, depending on arbitrarily defined cutoff rates), making
routine eosinophil testing unhelpful. Serum tryptase levels are vinblastine, 5-fluorouracil
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useful in reactions caused by diffuse mast cell (anaphylactic or anaphy- Acral erythema Cytarabine, doxorubicin, • Elevate the extremity
lactoid) activation, especially when hemodynamic changes are present. fluorouracil • Cold compresses
Tryptase is a protease stored in the granules of mast cells and released • Analgesics
with mast cell activation. Levels should be obtained within 2 hours of • Pyridoxine 150 mg daily
the anaphylactic episode. Serum tryptase concentrations are recom- Lower extremity Hydroxyurea, methotrexate • Discontinue the drug
mended over serum histamine concentrations due to the greater stability ulcerations
of tryptase. 12 Neutrophilic eccrine Cytarabine, bleomycin, • None
The clinical usefulness of in vitro diagnostic tests to detect the pres- hidradenitis cyclophosphamide, cisplatin,
ence of drug-specific antibodies capable of eliciting basophil histamine topotecan, anthracyclines
release, lymphocyte blast transformation, or complement activation
remains to be proven. These tests carry a low sensitivity, are currently a Causes flagellate streaks of hyperpigmentation.
used mainly as research tools, and therefore are not recommended for b Gingival bands.
routine clinical use. c Flag sign = horizontal hyperpigmented bands on blond hair.
Despite the different proposed mechanisms, overlap is common, and
one cannot infer the pathogenesis of an eruption by its morphology or such as attapulgite, magnesium/aluminum hydroxide, diphenhydramine
causative drug alone. The diagnosis of a drug-related dermatosis encom- elixir, benzocaine, and viscous lidocaine.
passes a complex mental algorithm of probability, time and causality, Candidiasis, with its white, adherent velvety plaques, and varicella
alternative diagnoses, and plausibility. zoster virus may also affect the inside of the mouth. Herpes simplex
■ CHEMOTHERAPY-INDUCED DERMATOSES usually affects the vermilion border of the lips, but in the immunosup-
pressed may cause indolent intraoral ulcers.
Cancer patients may be affected by cutaneous reactions of diverse Intravenous administration of chemotherapeutic agents may result
etiologies, including infections, paraneoplastic pemphigus, dermatomy- in extravasation into surrounding tissues. Severity depends on type,
ositis, graft-versus-host disease (GVHD), nutritional deficiency, metas- quantity, and concentration of drug, and disabling sequelae are
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tases, cutaneous neoplasms, radiation reactions, and administration of uncommon. Agents may be irritants (eg, bleomycin, carboplatin,
chemotherapeutic agents. Table 129-5 includes the most commonly cyclophosphamide, doxorubicin, etoposide, fluorouracil, paclitaxel, or
encountered chemotherapy-induced dermatoses. vinblastine), which cause sclerosis, hyperpigmentation, and tenderness
The most common CADR to chemotherapeutic agents is alopecia along the vein, or vesicants (eg, bleomycin, carmustine, cisplatin, doxoru-
(hair loss), which may present as anagen (hair growth phase) or telogen bicin, etoposide, fluorouracil, melphalan, mechlorethamine, mitomycin,
(hair resting phase) effluvium. Anagen effluvium is usually caused by paclitaxel, vinblastine, or vincristine), which cause burning, necrosis, and
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antineoplastic agents, which weaken the hair shaft, resulting in severe ulceration. Treatment consists of discontinuing the infusion, elevating
hair loss apparent 1 to 2 months after therapy. Telogen effluvium occurs the affected extremity, and applying local heat or cold. Heat should not
secondary to acute physical or psychological stress, malnutrition, or be applied when extravasation of vinca alkaloids occurs because this may
drugs. Spontaneous regrowth with drug discontinuation is the norm for cause ulceration. Surgical debridement and skin grafting may be needed
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both types of alopecia. Treatments are rarely successful. The effective- in persistent ulcers. Antidotes are also recommended (Table 129-6).
ness of 2% topical minoxidil has been inconsistent. 14,15 Localized or diffuse hyperpigmentation is a common CADR, as a
Adverse effects in the oral mucosa occur in 40% of patients as a result result of melanin, carotene, hemoglobin, or other pigment deposition.
of direct drug toxicity or indirectly via effects on the bone marrow. Characteristic gingival bands occur with cisplatin; horizontal hyper-
Stomatitis is a frequent complication leading to erythema, edema, ulcer- pigmented bands on blond hair (flag sign) with methotrexate; flagellate
ation, pain, burning, and xerostomia. Healing occurs within 2 to 3 weeks. streaks of hyperpigmentation with bleomycin; serpentine supravenous
Treatment consists of adequate oral hygiene and the use of topical agents hyperpigmentation primarily with 5-fluorouracil; pigmented nail bands

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