Hindawi BioMed Research International Volume 2019, Article ID 1268430, 11 pages https://doi.org/10.1155/2019/1268430

Review Article : Review of the Pathogenesis, Diagnosis, and Management

Ploysyne Rattanakaemakorn and Poonkiat Suchonwanit

Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Tailand

Correspondence should be addressed to Poonkiat Suchonwanit; [email protected]

Received 28 October 2018; Accepted 3 January 2019; Published 15 January 2019

Academic Editor: Jean Kanitakis

Copyright © 2019 Ploysyne Rattanakaemakorn and Poonkiat Suchonwanit. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Scalp pruritus is a frequent problem encountered in dermatological practice. Tis disorder is caused by various underlying diseases and is a diagnostic and therapeutic challenge. Scalp pruritus may be localized to the scalp or extended to other body areas. It is sometimes not only associated with skin diseases or specifc skin changes, but also associated with lesions secondary to rubbing or scratching. Moreover, scalp pruritus may be difcult to diagnose and manage and may have a great impact on the quality of life of patients. It can be classifed as dermatologic, neuropathic, systemic, and psychogenic scalp pruritus based on the potential underlying disease. A thorough evaluation of patients presenting with scalp pruritus is important. Taking history and performing physical examination and further investigations are essential for diagnosis. Terapeutic strategy comprises removal of the aggravating factors and appropriate treatment of the underlying condition. All treatments should be performed considering an individual approach. Tis review article focuses on the understanding of the pathophysiology and the diagnostic and therapeutic management of scalp pruritus.

1. Introduction symptoms [4]. Tis specifc problem was termed in previous articles as “itchy scalp,” “scalp pruritus,” or “pruritus capitis,” Pruritus, also known as , is an unpleasant sensation that depending on the authors’ preference. In addition, the term evokes a desire to scratch [1]. It is a major and distress- “trichoknesis” was introduced to describe itching sensations, ing symptom of various cutaneous and systemic diseases. which markedly increase by touching the hair [5]. Informa- Pruritus is one of the important symptoms in dermato- tion on scalp pruritus remains limited and quite complicated. logical practice and has a great impact on the quality of Terefore, this disorder is challenging and requires better life of patients. In the skin, several etiologic factors, such understanding of the clinical characteristics and underlying as , cutaneous sensory receptors, C nerve fbers, pathogenesis to establish efective diagnosis and therapeutic and cytokines, are involved in the pathogenesis. Pruritus approaches. Tis review article aims to provide the under- can be classifed into 4 categories based on its mechanisms: standing of the pathophysiology and the diagnostic and prurioreceptive, neurogenic, neuropathic, and psychogenic therapeutic management of scalp pruritus. pruritus [2]. Te disorder may be acute or chronic (more than 6 weeks duration) and can occur as generalized or localized. 2. Epidemiology Te scalp is one of the anatomical areas frequently man- ifested with pruritus. Te symptom is commonly associated Although scalp pruritus is a common problem, specifc with various scalp conditions, such as seborrheic epidemiological study of its prevalence is still limited. Te and psoriasis, but it ofen occurs without any visible skin occurrence of this disorder is reported only in case series lesion or pruritus on other body parts [3]. Systemic dis- and epidemiological studies of other conditions [6]. Te orders, particularly dermatomyositis, sometimes show that prevalenceofscalppruritusinpreviousliteraturerangesfrom scalp pruritus is one of the important treatment-resistant 13 to 45%. 2 BioMed Research International

Hoss and Segal reported that 2 of 11 patients with the contralateral spinothalamic tract. Te transmission can scalp dysesthesia manifest scalp pruritus [7]. A study from be inhibited by stimulating the A� sensory fbers through Singapore revealed a 13% prevalence of scalp pruritus among scratching, which is directed by motor refexes, known patients with generalized idiopathic pruritus [8]. In a ret- as the “gate control theory.” Various mediators, including rospective study of sensitive scalp involving 1,011 French histamine, serotonin, prostaglandin, acetylcholine, cytokines, subjects, itching scalp was reported in 25% of the participants opioids, and neuropeptides, participate in this mechanism [9]. Another survey study among the French population [14]. Neuropathic pruritus occurs along the neurological reported a 21.49% prevalence of scalp pruritus [10]. Further- pathway where the nervous system is damaged. It is fre- more, a large epidemiological study on the prevalence of quently associated with numbness and tingling. Tis type chronic pruritus involving 2,540 people found that 44.6% of of pruritus ofen occurs following conditions that cause subjects have scalp pruritus [11]. A cross-sectional study of nerve damage, such as herpes zoster, trauma, and notalgia 302 geriatric patients revealed a 28% prevalence of pruritus paresthetica. Neurogenic pruritus is mediated by opioid and on scalp area [12]. Among 860 hemodialysis patients, the serotonin receptors. It basically afects the central inhibitory prevalence of scalp pruritus was 43.2% [13]. circuits, which are related to the mechanisms of pruritus in patients with and chronic kidney disease. Psychogenic pruritus is commonly associated with chronic 3. Pathophysiology stress or psychiatric disorders, such as depression and delu- sion of parasitosis. Psychological factors may infuence itch Te pathophysiology of scalp pruritus is rarely investigated perception. due the complex and unclear nature of cutaneous and In addition to 4 major mechanisms, the scalp normal nervous systems. Although it is a frequent problem, its patho- fora is speculated to be an important factor that is involved physiology remains unclear. Various scalp structures and in the pathogenesis of scalp pruritus. Microorganisms, mediators are hypothesized to be involved in the pathogenic including Malassezia species, Propionibacterium species, and process. Terefore, determining the characteristics of scalp staphylococci, are commonly found on the scalp [20, 21]. skin anatomy and physiology is important to better elucidate Malassezia species are identifed as an aggravating factor the pathogenesis of scalp pruritus. in various pruritic skin conditions, including seborrheic Te characteristics of scalp skin are diferent from those dermatitis, pityrosporum folliculitis, and of other body parts. Scalp skin has abundant sensory inner- [22, 23]. Te high number of Malassezia species on the vation from the branches of the trigeminal nerve and blood scalp is believed to be the cause of seborrheic dermatitis vessels. It contains more hair follicles and more sebaceous by increasing interleukin- (IL-) 8 production level [24, 25]. glands and possesses specifc normal fora, resulting in sus- Moreover, the organisms contain lipase, which hydrolyzes ceptibility to certain dermatological problems. Te pruritus human sebum triglycerides into free fatty acids resulting in signal is generally transmitted mainly by small unmyelinated scalp irritation and infammation [26–28]. Staphylococci are C fbers that originate from the skin via the contralateral also hypothesized to be a factor involved in the mechanism spinothalamic tract to multiple brain areas that are responsi- of scalp pruritus. Staphylococcal exotoxins induce IL-31 ble for sensation and emotion. Moreover, several mediators, expression [29] and serine protease activation of protease- such as histamine, tryptase, substance P, bradykinin, and activated receptor-2 receptor [30], which are known pathways opioids, play a role in the mechanisms of pruritus [14]. of pruritus. Interestingly, aberrant C nerve fber function of the scalp Among the components of scalp skin, the stratum has been discovered in previous literatures that makes the corneum and sebaceous glands are important in the protec- scalp a unique entity in pruritus in comparison to other tion of the scalp from various factors. Te human scalp is body areas. Shelly and Arthur reported no itch response to exposed to environmental hazards, such as sunlight, blow- cowhage spicules on the occipital scalp [15]. Rukweid et al. drying, mechanical trauma, and hair care products, which subsequently reported that histamine-induced itch response cause scalp infammation. Stratum corneum acts as a barrier by using intradermal microdialysis on the scalp is less than to protect these exogenous factors. Defect of this layer on the forearm skin [16]. Furthermore, Bin Saif et al. reported the scalp causes scalp scaling and infammation. Sebaceous a signifcant insensitivity of C nerve fbers of the scalp glands produce sebum, which transfers to hair and scalp to various experimental itch induction compared with the surface, which is another scalp barrier to diseases caused by forearm [17]. It would be of great interest to explore the role bacteria and fungi [31, 32]. Patients who are sensitive to hair of C nerve fber function in various disorders that manifest dyes present lower level of scalp sebum [33]. scalp pruritus. Te pathophysiology of scalp pruritus can be explained using 4 major mechanisms, namely, prurioreceptive, neuro- 4. Classification of Scalp Pruritus pathic, neurogenic, and psychogenic, which could promote more than a single mechanism [18, 19]. Prurioreceptive Several classifcations have been introduced to categorize pruritus occurs when the itch is initiated within the skin by pruritus, depending on the diferent etiologies and clinical various infammatory dermatological conditions that trigger manifestations[1,34].Aspreviouslymentioned,thechar- the neurological pathway in the free nerve endings and then acteristic of scalp skin is diferent from that of other body received by the brain through the unmyelinated C fbers along parts. Te scalp comprises a complex neuroanatomy with BioMed Research International 3

Table 1: Proposed clinical classifcation of scalp pruritus.

Classifcation Associated disease Infammatory dermatoses: acne necrotica, alopecia areata, angiolymphoid hyperplasia with eosinophilia, atopic dermatitis, central centrifugal cicatricial alopecia, , discoid erythematosus, folliculitis decalvans, frontal fbrosing alopecia, insect bite, lichen planopilaris, , pityriasis amiantacea, psoriasis, red scalp disease, scars, seborrheic dermatitis, urticaria, xerosis Dermatologic conditions Infectious dermatoses: cutaneous larva migrans, folliculitis, impetigo, pediculosis capitis, scabies, tinea capitis Autoimmune dermatoses: bullous pemphigoid, dermatitis herpetiformis Neoplasms: leukemia cutis, lymphoma cutis Atypical facial neuralgia, brain and spinal cord injury, brain tumors, migraine headache, narrowing of the Neuropathic conditions bony foramina from osteoarthritis, post herpetic neuralgia, scalp dysesthesia, Wallenberg syndrome Cholestatic disease, chronic renal failure, dermatomyositis, diabetes mellitus, drug-induced pruritus Systemic conditions (dobutamine), eosinophilic arteritis of the scalp, Hodgkin and non-Hodgkin lymphoma Anxiety disorders, delusional parasitosis, depression, obsessive compulsive disorders, schizophrenia, Psychogenic conditions somatoform and dissociative disorders, tactile hallucinations Scalp pruritus of Sensitive skin undetermined origin an abundance of sensorineural organs. Terefore, the causes associated with scalp pruritus [46, 47]. An experimental of scalp pruritus are also diferent and arise from various study in patients with CCCA revealed the association of conditions. For diferential diagnostic purposes, the classi- disease severity with cowhage-induced itch [48]. Folliculitis fcation of scalp pruritus has been proposed based on the decalvans, a neutrophilic cicatricial alopecia, is also present potential underlying disease, which categorizes the condition with scalp pruritus [49]. into dermatologic, systemic, neuropathic, and psychogenic Other dermatologic conditions, such as infectious der- diseases [35]. In addition, the term “mixed” is used when matoses, autoimmune dermatoses, and neoplasms, can more than one underlying disease is identifed. “Pruritus of present with scalp pruritus. Te common infectious diseases undetermined origin” is used when no underlying disease can are pediculosis capitis and scabies that ofen occur in chil- be identifed [1, 36]. Te proposed clinical classifcation of dren. Cutaneous larva migrans of the scalp was also reported scalp pruritus is summarized in Table 1. in literature [50]. Red scalp disease, an unknown etiologic condition, presents a difuse erythema of the scalp with 4.1. Dermatologic Conditions. Among the infammatory der- pruritus [51]. matoses, seborrheic dermatitis is the most common disorder presented with scalp pruritus [20]. Te clinical presentation 4.2. Neuropathic Conditions. Pathologic involvement of is erythematous patches or plaques with scales on the scalp. small unmyelinated C nerve fbers is an important Dandruf, known as pityriasis capitis, is considered a mild mechanism in neuropathic conditions. Neuropathic pruritus form of seborrheic dermatitis, which presents scalp scaling of the scalp is commonly associated with diabetes mellitus without erythema. Te pathogenesis of seborrheic dermatitis and herpes zoster. Scribner revealed that several patients is mediated from interactions among scalp skin, sebum, who present scalp pruritus achieve a complete relief when Malassezia fungi, and the immune system [26]. Te histamine the underlying diabetes is controlled [52]. Postherpetic levelinthescalpskinishighinpatientswithseborrheic neuralgia (PHN) following herpes zoster was also reported dermatitis. Reduction of histamine levels is associated with to be associated with pruritus. Scalp pruritus is more likely a signifcant reduction in the intensity of pruritus [37]. to develop afer herpes zoster, particularly in the trigeminal Scalp psoriasis is another infammatory skin disease that (V1)dermatome[53,54].Aretrospectivestudyof600 commonly presents with scalp pruritus. Te scalp is the patients with PHN revealed that scalp pruritus ofen occurs most afected area in psoriasis [38]. A survey study of afer herpes zoster on the head, face, and neck [54]. Other 195 patients with psoriasis revealed that 58% of patients neuropathic conditions that were reported to be associated report scalp pruritus [39]. Other infammatory dermatoses with scalp pruritus are scalp dysesthesia [7], brain and spinal that are associated with scalp pruritus are atopic dermatitis cord injury [55], narrowing of the bony foramina from [39], contact dermatitis [9], pityriasis amiantacea [40], and osteoarthritis [55], Wallenberg syndrome [56], and brain angiolymphoid hyperplasia with eosinophilia [41]. tumors [57]. Scalp pruritus is also commonly reported in patients with cicatricial alopecia when infammation occurs. Lichen planopilaris (LPP) [42–44] and frontal fbrosing alopecia, 4.3. Systemic Conditions. Systemic diseases, including variant of LPP [45], were reported in approximately 70% chronic kidney disease, cholestatic liver diseases, and hema- and 67% of patients with scalp pruritus, respectively. Central tologic malignancy, are associated with chronic pruritus. centrifugal cicatricial alopecia (CCCA), a common cause of Te scalp is also one of the common parts complained by scarring alopecia in African American women, is frequently patients with systemic diseases. Other systemic conditions 4 BioMed Research International reported are drug-induced pruritus by dobutamine [58] and 5. Diagnostic Approach of Scalp Pruritus eosinophilic arteritis of the scalp [59]. Scalp involvement in dermatomyositis is common, and Te initial diagnostic approach in patients with scalp pruritus patients can present with scalp pruritus [60, 61]. Recently, includes history taking and physical examination to deter- scalp pruritus in dermatomyositis has been associated with mine whether the scalp pruritus is caused by a dermatologic small-fber neuropathy. A confocal image of immunostained condition or is secondary to other underlying conditions. Te scalp skin biopsies from a case of dermatomyositis with presence of a primary skin lesion suggests that evaluation severe scalp pruritus revealed decreased density and formed should focus on a dermatologic cause. In the absence of a complex tufs of epidermal nerves, which could explain the primary skin lesion, systemic conditions should be included mechanism of pruritus in patients with dermatomyositis [62]. in the evaluation process.

4.4. Psychogenic Conditions. Psychogenic factors, such as 5.1. History Taking. Te history taking for evaluating scalp anxiety, depression, and delusion of parasitosis, can be the pruritus should include information on the onset, afected cause of scalp pruritus. In any cases, the scalp is a frequent areas other than the scalp, type, severity, and aggravating and area of excoriations, possibly because this area is easily alleviating factors. A detailed history should focus on recent accessible. In patients with generalized pruritus, more than exposures to new possible aggravating factors, such as hair 10% are triggered by psychological factors [63]. Ferm et al. care products (e.g., shampoos, conditioners, hair styling aids, reported that the most commonly afected parts in patients hair dyes, cosmetics applied to the scalp), hair care practice, with psychogenic pruritus are the scalp and face. Teir and current medications. Environmental factors, including retrospective study of patients with chronic pruritus showed sun exposure, travel history, and occupational exposure, are that 16.7% of patients with psychiatric disease had pruritus also important to explore. History of contact with people of the scalp, which was also the most frequent afected area or animals with risk of exposure to infectious organisms, reported among psychiatric patients [64]. such as tinea capitis, pediculosis capitis, and scabies, is also In 2013, Reich et al. introduced the term “trichoknesis” important. In addition, the review of systems for underlying to describe itching sensations, which markedly increase by systemic disease should be performed, particularly for atopy, touching the hair [5]. Trichoknesis is considered a variant diabetes mellitus, thyroid diseases, hematologic malignancy, of trichodynia, a somatoform disorder, which is a painful chronic kidney disease, and cholestatic liver diseases. Patients sensation within hair that becomes more intense when with neuropathic scalp pruritus ofen present abnormal hairs are touched. However, since Ericson et al. discovered sensations, such as burning and stinging, along with pruritus. localization of substance P in the scalp of patients with Currently, no standardized method has been established to trichodynia [65], suggesting a causal relationship, its patho- evaluate the intensity of scalp pruritus. A visual analogue physiology is probably polyetiologic [66]. In addition, small- scale is a useful method to indicate pruritus intensity on a fber neuropathy, an alteration of the nervous system, was line, from 0 (no pruritus) to 10 (the worst pruritus) [74]. hypothesized to be one of the pathogenic processes of both trichodynia and trichoknesis [67]. 5.2. Physical Examination. Physical examination should focus on the dermatological system, particularly the hair and 4.5. Scalp Pruritus of Undetermined Origin. Scalp pruritus scalp area, for evidence of any recognizable skin conditions. with no underlying condition following completion of eval- Establishing whether scalp pruritus preceded the appearance uation is difcult to diagnose. Physicians ofen discuss with of a is important. Primary and secondary their patients and tell them that their scalp is sensitive. skin lesions need to be discriminated. Primary skin lesions Sensitive skin is characterized by complaints of discomfort originate from an underlying condition and are important for sensation, such as itching, burning, and stinging without evaluating the dermatological cause. Manipulations, such as predictable clinical signs [68, 69]. In this condition, the skin scratching and rubbing, can lead to secondary skin lesions, decreases its tolerance threshold against various triggering such as excoriation and lichenifcation, providing a chronic factors with no associated skin diseases [70, 71]. Scalp is course of the disease. Secondary skin lesions may resolve, one of the common afected areas of sensitive skin, the leaving dyspigmentation and scars. Moreover, evidence of so called “sensitive scalp.” Previous studies reported 32 to infection, particularly tinea capitis, pediculosis capitis, and 44% incidence of sensitive scalp [9, 72]. A study from scabies, should be examined. Bedside examinations, such as French population has identifed the triggering factors of dermoscopy, examination using a Wood’s lamp, and micro- sensitive scalp, including heat, cold, pollution, emotions, scopic examination, should be performed to help provide dry air, wet air, water, and shampoos [9]. In addition, hair defnite diagnosis. Although pruritus of systemic disease is dyeing products have been demonstrated to play a role in ofen generalized, it may sometimes present as localized increasing scalp sensitivity [73]. Scalp pruritus was reported pruritus. Terefore, a complete physical examination on as a symptom in 60% of patients with sensitive scalp; it was other body parts should be performed including an eval- found more in women than men and increased with age uation of the liver, spleen, and lymph nodes. Neurological [70]. However, the pathophysiology of sensitive scalp remains system evaluation is necessary in patients with suspected unclear. Categorizing the sensitive scalp into the proposed neuropathic scalp pruritus. Abnormalities in other systems classifcation is difcult, and the term “scalp pruritus of increase the possibility of underlying systemic diseases. How- undetermined origin” is suitable. ever, the presence of primary skin lesion does not exclude an BioMed Research International 5

Scalp pruritus

Primary skin lesions with No primary skin lesions with or without secondary skin or without secondary skin lesions present lesions present

Dermatologic cause Non-dermatologic cause

Detailed history and Detailed history and physical examination physical examination

Consider additional investigation: skin biopsy (histology and DIF) in uncertain case, skin scraping

Neuropathic cause Systemic cause Psychogenic cause

Consider additional Consider additional Drug history: Psychiatric investigation: CBC, investigation: NCS, drug-induced consultation BUN, Cr, , EMG, MRI ALP, TSH, FPG, ANA, anti-HCV, anti-HIV, CXR

DIF: direct immunofluorescence, NCS: nerve conduction study, EMG: electromyography, MRI: magnetic resonance imaging, CBC: complete blood count, BUN: blood urea nitrogen, Cr: creatinine, ALP: alkaline phosphatase, TSH: thyroid-stimulating hormone, FPG: fasting plasma glucose, ANA: antinuclear antibody, Anti-HCV: anti-hepatitis C virus antibody, Anti-HIV: anti-human immunodeficiency virus antibody, CXR: chest x-ray Figure 1: Diagnostic approach for scalp pruritus. underlying systemic disease, and the absence of primary skin antinuclear antibody, anti-hepatitis C virus antibody, anti- lesion does not imply that the causal condition is a systemic human immunodefciency virus antibody, and chest X- disease. ray. In patients with suspected neuropathic scalp pruritus, further investigations, such as nerve conduction study, elec- 5.3. Investigation. If the diagnosis remains unclear afer tromyography, and magnetic resonance imaging, may be history taking and physical examination, laboratory inves- indicated. tigation should be performed following the fndings of When all evaluations reveal negative results, patients with prior evaluation. An initial laboratory investigation con- chronic persistent scalp pruritus should be followed up with sists of complete blood count, blood urea nitrogen, crea- repeated evaluation. Te cause of scalp pruritus may present tinine, bilirubin, alkaline phosphatase, thyroid-stimulating later. Another point to consider is the presence of underlying hormone, and fasting plasma glucose. Further investiga- psychological problems, which should be addressed immedi- tions may include skin scraping and culture, skin biopsy, ately by referring the patient to a psychiatrist. Figure 1 outlines 6 BioMed Research International

Table 2: Principal topical medications for scalp pruritus.

Medication Dosage Adverse efects Many drugs with diferent doses; Skin atrophy, folliculitis, Glucocorticoids prefer using lotion, gel, and foam telangiectasia as vehicle Calcineurin inhibitors Pimecrolimus 1% Stinging or burning sensation Tacrolimus 0.03% - 0.1% Stinging or burning sensation Miscellaneous Menthol 1% - 5% Skin irritation Capsaicin 0.025% - 0.1% Burning sensation Liquor carbonis detergens 3% - 10% Skin irritation, stinging sensation Shampoos containing zinc Shampoos with anti-infammatory efects pyrithione, ketoconazole, Skin irritation, scalp dryness selenium sulfde, or coal tar a diagnostic approach for patients who present with scalp the treatment of scalp pruritus. Moreover, physicians should pruritus. educate and encourage their patients to use medications regularly as prescribed to achieve treatment efectiveness. 6. Management 6.1. Topical Terapy. An appropriate short acting method Management of scalp pruritus is challenging because it is to relieve acute scalp pruritus includes moisturizing with complex, multifactorial, and no generally accepted strategy scalp lotions and oily emollients containing glycerin or exists. Te principle of treatment includes removal of the panthenol that helps scalp dryness. Use of shampoo with an aggravating factors and appropriate treatment of the under- optimal pH (4.5-6.0) reduces the secretion of serine proteases lying condition. Topical therapy is the mainstay of treat- that can initiate scalp pruritus [75]. In addition, cooling ment. For widespread and recalcitrant diseases, a therapeutic scalp with menthol- or camphor-containing shampoo/lotion approach by combination of topical and systemic therapy is or using local anesthetics containing shampoo/lotion-like indicated. In addition, supportive therapy by other modalities polidocanol can temporarily reduce scalp pruritus. Poli- is necessary to maximize therapeutic outcome. Various treat- docanol, a protease-activated receptor-2 antagonist, is a ments have been introduced to treat scalp pruritus; however, nonionic surfactant with local anesthetic efect. Menthol the efcacy of these treatments on scalp pruritus is still provides efect by generating a cool sensation limited since pathophysiology of pruritus in most disorders via activation of transient receptor potential melastatin 8 is unclear. Hair care practices should be performed gently [76, 77]. However, careful use of menthol is necessary because by using hypoallergenic products and avoidance of chemical it can induce skin irritation. Cold compression may help irritants, fragrance, and hot blow-drying. Shampoos with relieve scalp pruritus. Studies on topical antihistamines reveal anti-infammatory efects, such as zinc pyrithione, ketocona- inefectiveness and may cause allergic contact dermatitis zole, selenium sulfde, and coal tar, can be used to reduce scalp [78]. Table 2 demonstrates a list of the principal topical infammation. Depending on the underlying mechanism, medications for scalp pruritus. therapeutic options used should be selected following the Topical corticosteroids can provide a quick relief from pathogenic process. Specifc treatment of a primary condition scalp pruritus in steroid-responsive dermatosis and are avail- ofen results in a relevant improvement of scalp pruritus. able in solutions, foams, and shampoos, which are convenient However, immediate improvement of scalp pruritus is more to use on the scalp. However, studies providing evidence important and is the frst step of the treatment plan. of a signifcant antipruritic efect in the treatment of scalp Notably, the characteristic of scalp skin can prevent pruritus rarely exist [79]. Terefore, single application of optimal treatment. Te presence of hair can interfere with topical corticosteroids for treating pruritus symptom is not treatment reaching the scalp, and scalp thickness decreases advised. Nevertheless, prolonged use of topical steroids on the penetration. Certain vehicles, such as ointment and scalp can induce skin atrophy. cream, can be messy to apply and adhere to the hair Te topical calcineurin inhibitors, tacrolimus and pime- shaf, resulting in a greasy appearance and decreased patient crolimus, were introduced for the treatment of atopic der- compliance due to cosmetic unacceptability. Terefore, the matitis. In addition to improving skin lesions, they also optimal vehicle can be as important as the active ingredient show antipruritic efect. Compared with capsaicin, an initial in achieving efcacy, tolerability, and adherence. Lotion, gel, burning and pruritus possibly occur, which may provide and foam are preferred vehicles owing to their superiority to clinical evidence for assumed transient receptor potential cream and ointment in the treatment within the scalp area. vanilloid 1 (TRPV1) binding. Topical calcineurin inhibitors Lack of medications in appropriate forms is also a problem in have been proven to be efective for various pruritic skin BioMed Research International 7

Table 3: Principal systemic medications for scalp pruritus.

Medication Dosage Adverse efects Antihistamines Chlorphenamine 4 - 16 mg/day orally Drowsiness, dry mouth Hydroxyzine 25 - 50 mg/day orally Drowsiness, dry mouth Diphenhydramine 25 - 100 mg/day orally Drowsiness, dry mouth Cetirizine 10 - 20 mg/day orally Drowsiness, dry mouth Loratadine 10 - 20 mg/day orally Drowsiness, dry mouth Fexofenadine 60 - 360 mg/day orally Drowsiness, dry mouth Levocetirizine 5 - 10 mg/day orally Unusual drowsiness, dry mouth Drowsiness, dry mouth, prolonged 25 - 100 mg/day orally QT interval Anticonvulsants Gabapentin 100 - 1200 mg/day orally Drowsiness, leg edema, constipation Pregabalin 25 - 200 mg/day orally Drowsiness, leg edema Opioids 0.2 mg/kg/min intravenous daily, Hepatotoxicity, nausea and Naloxone preceded by 0.4mg intravenous vomiting, insomnia bolus over 24 hours Hepatotoxicity, nausea and Naltrexone 12.5 - 50 mg/day orally vomiting, abdominal pain, diarrhea Drowsiness, nausea and vomiting, Butorphanol 1 - 4 mg inhaled at bedtime dizziness Antidepressants Drowsiness, dizziness, dry mouth, Amitriptyline 10-150mg/dayorally constipation Insomnia, dry mouth, sexual Paroxetine 10 - 40 mg/day orally dysfunction Mirtazapine 7.5 - 15 mg/day orally Drowsiness, weight gain, dry mouth Miscellaneous Cyclosporin A 3 - 5 mg/kg/day orally Nephrotoxicity, hypertension Teratogenic efect, peripheral Talidomide 100 - 200 mg/day orally neuropathy, drowsiness, constipation

conditions, such as nodularis and genital chronic It is ofen used to treat scalp seborrheic dermatitis and scalp pruritus [80], and could be an alternative option for scalp psoriasis. pruritus. However, medications are only available in ointment and cream which could difcult to use on scalp area. 6.2. Systemic Terapy. Systemic therapy is rarely indicated Capsaicin, a substance that binds to the TRPV1 receptor, in the treatment of scalp pruritus. However, this option is an option for the symptomatic treatment of neuropathic should be considered when topical therapy is inefective scalp pruritus. Topical capsaicin is available in solutions [83]. Currently, no study has investigated the efcacy of which is convenient to use on the scalp. Tis substance owes any systemic therapies for the treatment of scalp pruritus. its antipruritic mechanism to desensitization of the sensory However, initiation of systemic therapy is based on a step- nerve fber and interrupts the conduction of cutaneous by-step approach depending on the severity of scalp pruritus, pruritus. Terefore, topical capsaicin has been reported to the overall status of the patient, and expected adverse efects be efective in postherpetic neuralgia, notalgia paresthet- of the treatment. A list of the principal systemic medications ica, , , and prurigo for scalp pruritus is summarized in Table 3. nodularis [81, 82]. Antihistamines are frequently used in general practice Liquor carbonis detergens, a tar derivative, have an anti- for the treatment of various types of pruritus. Its mechanism infammatory and soothing efect to relieve scalp pruritus. of H1 receptor antagonists is speculated to be efective It can be alternatively used for resistant infammatory der- when pruritus is mediated by histamine. Antihistamines also matoses and is available in 3-10% solutions and shampoos. modulate immunological responses, such as mediator release, 8 BioMed Research International cytokines, and chemokines. Te role of antihistamines for reported in previous studies [95–98]. Although phototherapy the treatment of other pruritic disorders, other than urticaria has never been specifcally reported in the treatment of scalp and mastocytosis, remains controversial [84]. However, pre- pruritus, the use of targeted phototherapy or a UV-light comb vious studies suggested that high dosage or combination of may be considered in recalcitrant cases since the devices can antihistamines show efectiveness in the treatment of chronic improve the transmission of UV to the scalp surface. pruritus with diferent origins [85]. Anticonvulsants and pain modulators, such as gabapentin 6.4. Psychotherapy. Psychotherapies, such as behavior ther- and carbamazepine, which are inhibitors of the neuropathic apy, need to be considered to break the vicious circle of itching aferent pathway, are used for neuropathic pain and also have and scratching [99]. Some patients show an unconscious antipruritic efects [86]. Te antipruritic mechanism is still automatic scratching behavior. Te benefts of psychotherapy unknown, but it has been speculated to involve in both central include stress reduction and increased sense of control of and peripheral pathways. Gabapentin inhibits release of calci- scratching [100]. More importantly, the therapeutic strategies tonin gene-related peptide from primary aferent neurons by do not harm and are likely to improve patient quality increasing gamma-amino butyric acid in the spinal cord [87]. of life. In patients with underlying psychiatric disorders, Gabapentin should be considered as a treatment option in psychotherapy in combination with medical therapy can be patients with suspected neuropathic scalp pruritus; the dose helpful to treat scalp pruritus. of gabapentin is usually started low and titrated up to an efective dose [83]. Adverse efects reported include dizziness, peripheral edema, and worsening of diabetes mellitus. 7. Conclusion Opioid receptor antagonists, such as naloxone and nal- Scalp pruritus continues to be a major dermatological prob- trexone, infuence the neurogenic pruritus by inhibiting itch lem. It is a common and sometimes disabling symptom. transmission. Opioid receptor antagonists showed antipru- Te diagnostic approach to patients with scalp pruritus is ritic efects in , , and complicated and requires multidisciplinary interactions due various pruritic skin conditions, such as atopic dermati- to the complex neuroanatomy of the scalp and incomplete tis, bullous pemphigoid, cutaneous lymphoma, and prurigo understanding of the pathogenesis. Although the under- nodularis [88]. Tese antagonists should be considered as standing of the pathogenesis of scalp pruritus has improved a treatment option for neuropathic scalp pruritus. Adverse signifcantly in recent years, it remains one of the great efects, such as nausea and vomiting, are reported in the frst challenges for medical research. Further investigation and few days. determining more efective antipruritic agents with lower Antidepressants directly infuence central pruritus by adverse efects are necessary. unknown mechanisms. Teir mechanism is speculated to interfere in the neuronal reuptake of neurotransmitters, such Conflicts of Interest as serotonin and norepinephrine. Tricyclic and tetracyclic antidepressants have been reported to be efective. Amitripty- Te authors report no conficts of interest. line is useful in some cases of neuropathic pruritus. Doxepin and mirtazapine possess additional antihistaminic efect [89, 90]. Selective serotonin reuptake inhibitors reveal similar References efects with a better safety profle. Paroxetine has antipruritic [1] S. St¨ander, E. Weisshaar, T.Mettang et al., “Clinical classifcation efect in patients with various types of nondermatologic of itch: a position paper of the international forum for the study pruritus [91]. of itch,” Acta Dermato-Venereologica,vol.87,no.4,pp.291–294, Te other medications that may be considered for treat- 2007. ment of scalp pruritus with special caution are cyclosporin [2] R. Twycross, M. W. Greaves, H. 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