For many skin diseases, pruritus is a significant symptom. The diseases featuring pruritus include autoimmune, genetic, infectious, inflammatory, neoplastic, and pregnancy-related dermatoses. Epidemiologic statistics have been reported for some of these diseases. Pruritus is one of the major diagnostic criteria for atopic dermatitis, a disease which afflicts 11 % of people under 18 years of age (Shaw et al. 2011). In elderly patients with xerosis, 30–60 % experience pruritus (Beauregard and Gilchrest 1987). Another common cause of pruritus is urticaria, which has a lifetime prevalence of 15–20 % in the general population (Soter 1998; Bakker et al. 2013). In patients with psoriasis involving more than 30 % of their skin, 80 % experience itch (Yosipovitch et al. 2000; Krueger et al. 2001). Cutaneous T-cell lymphoma, although rare, is associated with significant pruritus with one study reporting 88 % of their 100 patients with pruritus in the preceding 4 weeks and 46 % indicating that it was often or always a problem (Wright et al. 2013). Contact dermatitis, keloids, and scars are also associated with itch, but the prevalence of itch in these conditions is unknown (Herman 1994; Yosipovitch 2003). Rare skin diseases are also anecdotally reported with pruritus as a significant symptom such as bullous pemphigoid (Bakker et al. 2013), dermatitis herpetiformis (Powell et al. 2004; Passe et al. 2008), and lichen planus (Welz-Kubiak and Reich 2013). However, epidemiologic studies in such rare entities are very difficult to perform.

Chronic pruritus is frequently present in systemic disease (Cassano et al. 2010). Studies have found that 10–50 % of patients with pruritus and no skin findings have an underlying systemic disease, and up to 70 % of these patients have a psychiatric disease (Ferm et al. 2010). Different studies identified systemic causes of chronic pruritus in 14–50 % of patients (Rajka 1966; Beare 1976; Kantor and Lookingbill 1983; Zirwas and Seraly 2001; Afifi et al. 2004). Three studies of patients presenting with pruritus found that 24 % to 57 % of cases were due to dermatoses (Lyell 1972; Weisshaar et al. 2006; Sommer et al. 2007). When the patients with dermatoses were excluded, 31 % of the patients of Lyell and 82 % of the patients of Weisshaar et al. had an underlying systemic disease. A retrospective case review of patients with chronic pruritus revealed that the most severe and long-lasting pruritus occurred in patients with multiple systemic diseases and in those patients where the etiology of pruritus was unknown. Of 139 patients with itch, 47 had one systemic disease, 9 had two or more internal diseases, 24 had neuropathic itch, 31 had psychiatric disease, and 37 had pruritus of unknown origin. Scalp and face pruritus was most common in patients with psychogenic pruritus. The authors concluded that work-up of a patient with chronic pruritus rarely reveals an underlying systemic disease which is responsible for their pruritus (Ferm et al. 2010).

In end-stage renal disease (ESRD), pruritus occurs independent of the etiology of the renal failure. All races, ages, and both genders are susceptible to ESRD pruritus (Senturk et al. 2008). The pathogenesis is unknown but is associated with an elevated C-reactive protein as well as other inflammatory cytokines. The renal failure must be severe to be associated with pruritus and resolves after renal transplant (Berger and Steinhoff 2011). Narita and colleagues found pruritus in 15–49 % of patients with chronic renal failure and 50–90 % of patients undergoing dialysis (Narita et al. 2008). Zucker and colleagues similarly found 66 % of patients undergoing hemodialysis experienced pruritus at some point (Zucker et al. 2003). The ITCH National Registry Study was a prospective, multicenter, longitudinal study of 103 hemodialysis patients. In this group, daily or almost daily itching was reported by 84 % of patients (Mathur et al. 2010). The Observational Dialysis Outcomes and Practice Patterns Study collected data from over 29,000 hemodialysis patients in 12 countries and found that 42 % of these patients experienced moderate to extreme itch during the year they were followed (Pisoni et al. 2006). Other studies reported a pruritus prevalence of 25–86 % in ESRD patients (Young et al. 1973; Bencini et al. 1985; Szepietowski and Schwartz 1998; Zucker et al. 2003; Duque et al. 2006). Differences in pruritus prevalence were found between countries: 38 % in France, 45 % in Japan and the United States, 48 % in the United Kingdom, 49 % in Germany, and 55 % in Italy (Pisoni et al. 2006; Wikström 2007). Tessari et al. saw that 52 % of dialysis patients experience pruritus, with no difference in prevalence between hemodialysis and peritoneal dialysis patients (Tessari et al. 2009). Those patients dialyzed with less permeable and less biocompatible membranes have a lower incidence of pruritus (Murphy and Carmichael 2000; Pauli-Magnus et al. 2000). Additionally, patients on statins are significantly less likely to suffer from pruritus (p = 0.02) (Duque et al. 2006). In patients undergoing hemodialysis, chronic pruritus was associated with poor outcomes (Narita et al. 2008).

The reported prevalence of chronic pruritus in hepatic disease ranges from 15 % to 100 % (Weisshaar and Dalgard 2009). Itching is a frequent symptom of cholestasis occurring in 80–100 % of cases (Bergasa et al. 2000). Pruritus is seen in 5 % of patients with chronic hepatitis (Chia et al. 1998) and 15 % of patients with chronic hepatitis C infection (Maticic et al. 2008). Pruritus is the presenting symptom of primary biliary cirrhosis in 25–70 % of patients, and 10 years after, diagnosis is present in at least 70 % of patients (Heathcote 1997; Bergasa et al. 2000; Mela et al. 2003; Talwalkar et al. 2003). In an online survey, 69 % of women with primary biliary cirrhosis experienced pruritus, and of these women, 75 % experienced itch prior to their diagnosis (Rishe et al. 2008). A case control study of 49 patients with primary biliary cirrhosis echoed these results with a pruritus prevalence of 69 % (Koulentaki et al. 2006).

Hematologic abnormalities can engender pruritus. In a meta-analysis of 10 studies, Saini and colleagues (Saini et al. 2010) found pruritus in 42 % of 821 patients with polycythemia vera. Other investigators found that half of patients with polycythemia vera experience pruritus (Diehn and Tefferi 2001; Vannucchi et al. 2007). Lower mean corpuscular volume and a higher leukocyte count are significantly associated with the presence of pruritus in patients with polycythemia vera (Diehn and Tefferi 2001). In a recent study of 441 polycythemia vera patients, 68.2 % reported aquagenic pruritus (Siegel et al. 2013).

Iron deficiency may play a role in chronic pruritus (Diehn and Tefferi 2001). In a prospective study assessing the frequency of systemic disease in patients with generalized pruritus (n = 55), iron deficiency anemia was found to be the most common cause of generalized pruritus. The mean serum hemoglobin, iron, and cyanocobalamin were significantly lower in the patients with generalized pruritus as compared to the control group (Polat et al. 2008). Additional studies have similarly reported iron deficiency in association with chronic pruritus (Bharati and Yesudian 2008).

Pruritus is associated with hematologic malignancies and less commonly with solid tumors. Thirty percent of Hodgkin’s lymphoma patients report itch (Goldman and Koh 1994). Patients with chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin lymphoma also report pruritus; occasionally, pruritus is the presenting symptom (Daponte et al. 2007; Robak and Robak 2007). Solid tumors, including breast, lung, colon, and prostate neoplasms, represent a rare cause of chronic pruritus (Kleyn et al. 2006). While malignancy-associated itch is usually generalized, in some cases, it is associated with the location of the tumor, which may be due to direct activation of the nerves (McMichael 2004). In contrast, Yosipovitch (2010) described paraneoplastic itch as a distinct entity which is not caused by tumor invasion or compression, occurs early in the natural process of the malignancy, and subsides after the removal of the tumor.

Infectious diseases are also known to engender pruritus, including viral and parasitic infections, as well as skin diseases in HIV patients such as eosinophilic folliculitis and papular pruritic eruption of HIV (Bonacini 2000; Rodwell and Berger 2000; James et al. 2005). Pruritus is also associated with endocrine disorders including hyperthyroidism and diabetes (Jabbour 2003).

Pruritus is a common symptom after burns. In a multicenter cohort study of adult burn survivors, the prevalence of itch at discharge, 6, 12, and 24 months after injury, was 93 %, 86 %, 83 %, and 73 %, respectively. In a group of patients burned 4–10 years ago, 44.4 % reported itching at the area of previous injury (Carrougher et al. 2013).

Pruritus occurs in psychiatric diseases. In a study of 100 inpatient psychiatric patients, 42 % suffered from idiopathic pruritus. Idiopathic pruritus was related to psychosocial stressors, with 29.5 % and 48.5 % prevalences in patients with and without adequate social support, respectively (p = 0.02). Additionally, 48.5 % of patients not regularly employed experienced pruritus compared to 16.7 % of those with regular employment (p = 0.01). This study also found that tricyclic antidepressants reduce pruritus prevalence from 48 % to 14 % (p = 0.09) (Kretzmer et al. 2008). In a similar study, 111 inpatient psychiatric patients at an Israeli hospital were administered a validated itch questionnaire; 32 % of the patients reported pruritus despite few seeking treatment for their pruritus (Mazeh et al. 2008).

Neurologic disease can engender pruritus. Patients who suffer from postherpetic neuralgia following a shingles infection may additionally report postherpetic itch or may only experience itch instead of pain. Oaklander et al. (2003) reviewed three previously collected data sets of patients with recent shingles infection or postherpetic neuralgia from Finland, Seattle, and Liverpool for a sample of 586 individuals to better characterize the epidemiology of postherpetic itch. They found pruritus commonly occurs with postherpetic neuralgia as well as with acute zoster infections. Patients who had shingles on their head, face, and neck were more likely to suffer from postherpetic itch compared to those who only had singles on the torso. In a study looking at the point prevalence of pruritus in people with recent shingles, 17 % of adults from Finland reported itch, 36 % from Liverpool, and 58 % from Seattle (Oaklander et al. 2003). Neuromyelitis optica has also been associated with pruritus; in a small study of 44 patients, 27.3 % reported pruritus (Elsone et al. 2013).

Collagen diseases such as scleroderma and dermatomyositis have a relatively high prevalence of chronic pruritus. Of 959 patients in the Canadian Scleroderma Research Group Registry, 42.6 % reported pruritus during the past month on most days (Razykov et al. 2013). Similarly, a retrospective 30-year chart review of 16 patients with juvenile dermatomyositis revealed pruritus was a symptom in 38 % of patients (Peloro et al. 2001).

Many medications cause pruritus. This pruritus may be secondary to a cutaneous drug reaction (e.g., urticaria), but medications can also provoke pruritus without signs of skin irritation (Reich et al. 2009). For example, 10–50 % of patients receiving intravenous opioids experience pruritus, as do 20–100 % of patients receiving intraspinal or epidural opioid injections (Ganesh and Maxwell 2007). While the exact mechanism for opioid-induced pruritus is not fully understood, μ opioid receptor agonists play a significant role, while serotonin and dopamine D2 receptors appear to play a role as well. Pruritus is also estimated to affect 5–27 % of patients in palliative care. The etiology is complex and possibly due in part to medications (Kleyn et al. 2006).

To understand the QoL impact of pruritus, readers must appreciate the instruments that have been developed to measure such impact. Early researchers utilized proxies to investigate the impact of pruritus such as agitation, poor concentration, anxiety, and depression (Gupta and Gupta 2004; Evers et al. 2005; van Os-Medendorp et al. 2006; Dalgard et al. 2007; Amatya et al. 2008; Zachariae et al. 2008). In an effort to more directly and effectively evaluate the influence of pruritus on QoL, researchers have developed and utilized validated instruments that quantify QoL impact. There are generic, skin-specific, and pruritus-specific instruments used to measure the impact of pruritus. The two commonly used generic tools are the Short-Form 12 and 36. The Short-Form 36 (SF-36) was developed from the Medical Outcomes Study and is a measure of health status consisting of eight domains: physical functioning, limitations due to physical health, limitations due to emotional health, energy level, emotional well-being, social functioning, pain, and general health. The SF-36 has also been condensed into a 12-item version, SF-12, which assesses both physical and mental health. The components of the SF-12 measure general health, daily and social activity limitations as a result of physical and/or mental health, impact of pain on normal work, feelings of calm and peace, energy, and downheartedness (Chen 2012).

The two most commonly used skin-specific instruments are Skindex and the Dermatology Life Quality Index (DLQI), which both ask questions related to pruritus. Skindex-29 asks the frequency of “My skin itches” and Skindex-16 queries “During the past week, how often have you been bothered by your skin condition itching?” (Chren et al. 1997, 2001). Numerous studies have utilized this instrument to investigate the impact of pruritus on QoL, including research into antihistamines (Murota et al. 2010), chronic venous insufficiency (Duque et al. 2005), and dialysis (Tessari et al. 2009). The DLQI is the most frequently used skin-specific QoL questionnaire. DLQI addresses pruritus by asking “Over the last week, how itchy, sore, painful or stinging has your skin been?” (Chen 2012; Finlay and Khan 1994). Investigators have used DLQI to evaluate the impact of pruritus on QoL in multiple studies, including research into ESRD (Szepietowski et al. 2011) and vitiligo (Silverberg and Silverberg 2013). A pediatric version of the DLQI, the Children’s Dermatology Life Quality Index (CDLQI), has been created as well.

Pruritus-specific instruments have been developed and validated to better assess the impact of pruritus. Yosipovitch and colleagues developed the Short-Form Itch Questionnaire, modeled after the Short-Form McGill Pain Questionnaire. The questionnaire includes QoL questions on mood, eating habits, sexual desire and function, and sleep (Melzack 1975; Yosipovitch et al. 2001; Ikoma et al. 2006), but does not fully address all QoL constructs. Studies using the questionnaire include studies of psoriasis patients (Yosipovitch et al. 2000), chronic idiopathic urticaria (Yosipovitch et al. 2002a), and atopic dermatitis (Yosipovitch et al. 2002b). Majeski et al. (2007) modified the Short-Form Itch Questionnaire into the Itch Severity Scale, which also measures the severity and patient burden of pruritus but, unlike the former, does not require interviewer administration.

A more comprehensive validated pruritus-specific QoL instrument is the ItchyQoL, which addresses the symptom, emotional, and functional impact of pruritus. Studies which have utilized ItchyQoL include a small cohort of patients with cutaneous T-cell lymphoma (Chen et al. 2010). ItchyQoL has been translated into German and studied in a cohort of 308 patients with pruritus of diverse etiology: urticaria, atopic eczema, psoriasis, prurigo, renal disease, liver disease, neoplasm, and unknown etiology (Krause et al. 2013).

Other pruritus-specific instruments used in QoL studies include the Eppendorf Itch Questionnaire (Darsow et al. 1997), 5-D itch scale (Elman et al. 2010), and Patient Benefit Index for pruritus (Blome et al. 2009). Weisshaar and colleagues (2011) recently developed a German language questionnaire assessing for chronic pruritus with the goal of usage in epidemiologic studies. The questions assess the course, intensity and quality of pruritus, general health status, sociodemographic data, QoL, and pruritus cognition. Other studies utilize consolidated summary measures of QoL including health economic utilities (Kini et al. 2011) and general questions such as “Has your life changed?” (Weisshaar et al. 2006).

Pruritus has been repeatedly demonstrated to have a significant impact on QoL (Gupta et al. 1994; Yosipovitch et al. 2000, 2002b; Radmanesh 2001; Zucker et al. 2003; Chamlin et al. 2005; van Os-Medendorp et al. 2006; Goon et al. 2007; Wikström 2007; Amatya et al. 2008; Yamamoto et al. 2009). Indeed, the impact of chronic pruritus on QoL has been found not significantly different from the impact of chronic pain on QoL (Kini et al. 2011) with 73 chronic pruritus study patients willing to give up 13 % of their lives to not have pruritus. Halvorsen et al. (2009) found that there was a 3.0 odds (confidence interval: 2.1–4.2) to have suicidal ideation associated in adolescents with chronic itch compared to adolescents without itch, which was comparable to the odds from chronic pain.

A Dutch study found that 13 % of their 167 chronic pruritus patient cohort sought a mental health professional that resulted with 4.8 % prescribed tranquilizers and 6.2 % with antidepressants. Their research suggested that the coping strategy adopted by patients is more responsible for this impact than the pruritus itself; catastrophizing and helpless coping have been found to play a greater role in morbidity from pruritus than itch frequency (van Os-Medendorp et al. 2006). Other studies have also indicated that a support structure may be beneficial as marital status seems to confer a positive impact in pruritus-specific QoL (Kini et al. 2011; Carr et al. 2014).

The deleterious impact of pruritus on QoL has been demonstrated in many different populations. For example, Weisshar and colleagues (2006) compared two populations with pruritus, one in Germany (132 patients) and one in Uganda (84 patients). Patients in both populations exhibited an impaired QoL. Interestingly, while the majority of the etiology of pruritus in these two populations was from a dermatosis, it was the pruritus of unknown origin that led to the greatest QoL impact.