Pruritus

Pruritus

David Croitoru

Ehsan Azimi

Maxwell B. Sauder

The experience of pruritus among cancer patients is common, frequently leads to decreased quality of life, and may be related to multiple factors associated with oncogenesis, secondary organ impairment as well as anticancer therapy. The dichotomy between the reward of scratching and noxiousness of itch may lead to negative behavioral cycles that interfere with routine daily and nocturnal function. Cross-sectional and prospective studies have demonstrated generalized pruritus around 13% in untreated cancer patients,¹ with an incidence of as high as 17.9% to 36% while undergoing treatment with systemic therapy.²,³

While the most common cause of itch in the cancer population, like the general population, is xerosis,⁴ a thorough history and investigation is necessary to rule out additional actionable contributors. Systemic cancer therapies vary in their likelihood of inducing pruritus, with some treatment classes having pruritus as a significant contributor to their adverse event profile (Table 44.1). For example, pruritus is the second most common
cutaneous adverse event across immune checkpoint inhibitors and most common with CTLA-4 inhibitors.⁵,⁶ In addition to anticancer therapy-induced itch, other causes of pruritus include new onset or exacerbation of preexisting inflammatory dermatoses, paraneoplastic causes, systemic or metabolic mediators, infection-related, as well as ancillary medication effects such as those used to treat pain (Table 44.2).

TABLE 44.1 • Anticancer Therapy Classes Associated with Pruritus

Alkylating agents
Androgen-deprivation agents
Aromatase inhibitors
B-Raf inhibitors
Epidermal growth factor 1 (EGFR) and 2 (Her-2) receptor inhibitors
Immune checkpoint inhibitors
Mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) inhibitors
Mammalian target of rapamycin inhibitors
Multikinase inhibitors
Radiation therapy
Selective estrogen receptor modulators (SERMs)
Taxanes
Topoisomerase II inhibitors
Vascular endothelial growth factor receptor inhibitors

TABLE 44.2 • Nontherapeutic Causes of Pruritus in Cancer Patients

Inflammatory dermatoses	Dermatitis (atopic, irritant, allergic contact), psoriasis, pityriasis rubra pilaris, autoimmune bullous disease, lichen planus, drug reactions, urticaria, autoimmune connective tissue diseases, solar dermatoses
Paraneoplastic pruritus	Sézary syndrome, Hodgkin lymphoma, non-Hodgkin lymphoma, hypereosinophilic syndrome, primary cutaneous carcinomas, adenocarcinomas, sarcomas, plasma cell dyscrasias, mastocytosis, other hematologic dyscrasias
Metabolic pruritus	Hyperbilirubinemia; elevated bile acids; thyroid/parathyroid dysregulation; neuropathic, serotonergic, renal dysfunction; iron deficiency
Infections	Bacterial, viral, fungal, parasitic
Infestations	Scabies, pediculosis, arthropod assault

INITIAL ASSESSMENT

The International Forum for the Study of Itch (IFSI) has proposed dividing itch into three major categories: itch affecting inflamed skin, itch affecting noninflamed skin, and itch resulting from a chronic itch-scratch cycle. Initial evaluation should include a detailed history with attention to dermatologic conditions preceding the cancer diagnosis, both to establish a baseline and understand the likelihood of a predisposing dermatosis.⁷ The duration and onset of itch may help with identifying an allergen exposure, for example hours in the case of urticaria, days in the case of contact allergens, and weeks in the case of certain drug reactions. A thorough cancer history including staging, with attention to onset and temporal association with therapeutic interventions, is needed to rule out a dermatologic adverse event. The number of cancer therapies implicated in the development of pruritus due to induction of xerosis or inflammatory dermatoses is vast.⁸ Therapeutic classes vary in their clinical course; however, 2 to 6 weeks has been suggested as a general guide for establishing a chemotherapeutic cause.⁵ Rechallenge evidence and lack of alternative causes can improve diagnostic specificity.

PHYSICAL EXAMINATION

Applying a framework based on IFSI categories (inflamed skin, noninflamed skin, and secondary self-induced lesions) helps to hone pretest etiology prior to a thorough physical examination and investigations.⁹ A full-body skin exam should be performed, noting
any cutaneous findings. If there are cutaneous findings, the morphology and distribution can provide further clues as to etiology (Table 44.3). Testing for dermatographism by firmly stroking the skin with the back of pen to look for a wheal-flare response (Figure 44.1) in all patients, even those with no active urticarial plaques or a known history of hypersensitivity, is recommended. Inspection for signs of systemic disease such as volume overload, hepatobiliary insufficiency or hemolysis, uremia, and thyroid dysfunction should inform metabolic testing. Lymph node and hepatosplenic exams are recommended, as pruritus has been associated with increased burden of disease and poor outcomes in hematopoietic neoplasms, such as cutaneous T-cell lymphoma and Hodgkin lymphoma.¹⁰ Patients with pruritus in noninflamed skin and those with secondary lesions may present with excoriations, sparing areas difficult to reach (Figure 44.2), prurigo nodularis, or evidence of chronic rubbing—lichen simplex chronicus (Figure 44.3) in the absence of other primary lesions.

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