Pruritus is a common and often times difficult to treat symptom in many dermatologic and systemic diseases. For pruritus with an inflammatory or autoimmune origin, therapies such as topical ...corticosteroids and antihistamines are often initiated. However, in the case that these and additional systemic therapies are ineffective, thalidomide, an immunomodulator and neuromodulator, may be a useful alternative treatment. Considerable relief of chronic pruritus has been demonstrated with thalidomide in case reports, case series, and controlled trials. Double-blind controlled studies demonstrated thalidomide's efficacy as an antipruritic agent in patients with uremic pruritus, primary biliary cirrhosis, and prurigo nodularis. In case reports, case series, and open-label trials, thalidomide significantly reduced pruritus associated with conditions such as actinic prurigo and paraneoplastic pruritus. Because of variations in study design and evaluation of antipruritic effect, it is difficult to fully understand thalidomide's role based on the evidence described to date in the medical literature. In this review, we provide an overview of the reported findings and evaluate thalidomide's utility in managing refractory pruritus in the context of its adverse risk profile. We propose that thalidomide can be an alternative or combination antipruritic treatment for patients who do not obtain enough relief from conservative therapy.
Itch, or pruritus, is the uncomfortable sensation underlying the desire to scratch. Itch is a very common complaint in the general population that can result from dermatologic, systemic (eg, renal, ...hepatobiliary, endocrine), paraneoplastic, neuropathic, and psychogenic etiologies. Chronic itch is associated with significant sleep disturbances and profoundly reduces overall quality of life. Certain populations, including elderly and African Americans, are at increased risk of experiencing heightened burden of itch. Because of the variable clinical presentation and wide-ranging etiologies, itch presents a challenge for clinicians. The initial evaluation should include a complete blood count, with differential, hepatic, renal, and thyroid function testing along with diabetes screening. Further testing should be guided by history and physical examination findings. There should be a heightened concern for underlying malignancy in individuals older than 60 years of age who have a history of liver disease and diffuse itch less than 12 months of duration. For individuals with chronic pruritus of unknown origin, increased blood eosinophils may serve as a biomarker of T helper cell type 2 polarization and response to immunomodulator therapies. In this first part of a 2-part continuing medical education series, we describe the broader epidemiology and specific conditions associated with itch and the clinical presentation and diagnostic workup for patients with itch.
Itch: Pathogenesis and treatment Sutaria, Nishadh; Adawi, Waleed; Goldberg, Rebecca ...
Journal of the American Academy of Dermatology,
January 2022, 2022-01-00, 20220101, Volume:
86, Issue:
1
Journal Article
Peer reviewed
Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein–coupled receptors and transient receptor potential ...channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.
Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers ...to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.
Prurigo nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life.
To characterize the demographics and comorbidities associated with PN.
Cross-sectional ...study of patients 18 years and older who were seen at the Johns Hopkins Health System between December 6, 2012, and December 6, 2017.
Over the past 5 years, 909 patients with PN were seen at Johns Hopkins Health System. African American patients were 3.4 times more likely to have PN than white patients were (odds ratio OR, 3.4; 95% confidence interval CI, 2.9-3.9; P < .001). A comparison of the study patients and race-matched controls revealed that PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities, including chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR, 10.5; 95% CI, 7.9-13.9; P < .001) to have HIV than were race-matched controls with atopic dermatitis, and 8 times more likely (OR, 8.0; 95% CI, 5.7-11.1; P < .001) to have HIV than were African American patients with psoriasis.
Our data describe patients seen by 1 hospital system. Our data identify associated conditions and comorbidities but are unable to support a causal relationship.
PN disproportionately affects African Americans and is associated with several systemic conditions, including HIV, chronic kidney disease, and diabetes.
Prurigo nodularis (PN) is a chronic disease characterized by intensely pruritic, raised, nodular lesions. Because there are currently no United States Food and Drug Administration-approved therapies ...specifically for PN, management is highly variable, and no consensus exists on treatment regimens.
To provide practical guidance to help United States dermatologists diagnose and effectively treat patients with PN.
We participated in a roundtable discussion to develop consensus recommendations on diagnosis and treatment of PN from a United States perspective.
The core findings in PN are the presence of firm, nodular lesions; pruritus lasting at least 6 weeks; and a history or signs, or both, of repeated scratching, picking, or rubbing. The diagnostic workup involves a complete review of systems, considering potential systemic diseases, and assessment of disease severity, including disease burden and pruritus intensity. Treatment should be selected based on a patient's clinical presentation, comorbidities, and response to prior treatments and should address both neural and immunologic components of pruritus.
Data on PN are from anecdotal or small clinical trials, and all treatments are currently used off-label.
An effective treatment approach for patients with PN should be based on clinical judgment and tailored to the individual needs of the patient.
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