Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management

Sensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.


Introduction
Although the complaint of sensitive scalp (SSc) is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature, where it had no clear definition until recently.The most complete definition of SSc was stablished in 2017 in the International Forum for the Study of Itch and is the same used for sensitive skin (SSk).SSk is "a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations.These unpleasant sensations cannot be explained by lesions attributable to any skin disease.The skin can appear normal or be accompanied by erythema.SSk can affect all body locations, especially the face" [1].
The first study that addressed SSc characteristics was an opinion poll published by Misery et al. [2].Of a sample of 1,011 participants representative of the French population, aged 15 years or older, 44.2% of the subjects selfdeclared having a sensitive to a very SSc, with a higher frequency in women.The authors associated SSc with atopic dermatitis and with SSk in other body areas [2].Previously, a study in SSk reported patients with scalp symptoms associated with the use of hair products [3].More studies were published but still in smaller numbers than the ones investigating skin.As scalp sensitivity has its particularities and may be associated with hair loss, it is important to be studied independently from the skin.We review the publications in this topic to gather the knowledge of epidemiology, etiopathogenesis, classification, clinical manifestations, diagnosis, and management of patients presenting with this disorder [2][3][4][5][6][7][8][9][10][11][12].

Epidemiology
SSc is a frequent complaint in the general population, which prevalence varies between 30 and 50% of individuals [2-5, 12, 13], as shown in Table 1.It is more commonly observed in female patients [2,4,12].Some authors suggest that women perceive skin changes more than men and tend to be more bothered by them [2].Although Misery et al. [2] identified in 2008 a highest scalp sensitivity in patients over 50 years old, other papers did not find a predominance in a specific age group.

Etiopathogenesis and Triggers
SSc can be triggered by several factors, both endogenous and exogenous.The main endogenous factors are emotional stress and hormonal changes, such as the menstrual cycle [2,14].As for exogenous triggers, environmental stimuli (ultraviolet radiation, heat, cold, wind, pollution), cosmetics (shampoos, hair conditioners, and others hair care products), spicy foods, and alcohol  [2,4,10,14].Another possible irritative trigger is topical minoxidil, frequently used in alopecias [13].The etiopathogenesis is still uncertain, but it is believed that the same mechanisms involved in SSk are associated in SSc [13,15].

Neurosensorial Mechanisms
It was hypothesized that SSk is characterized by a hyperreactivity of the cutaneous nerve endings [13,15].It was proposed that transient receptor potential (TRP) channels, expressed on the membrane of group C nerve fibers, play a central role in the skin sensitivity pathophysiology [16].The TRPV1 is expressed in nerve endings, epidermal keratinocytes, dermal mast cells, sebaceous gland-derived sebocytes, and dendritic cells.In fact, the vanilloid receptor 1 (TRPV1) has been appointed as the main mediator of this process as it can be activated by the triggering factors [16].
Immune Response TRPV1 channels' activation induces the release of substance P, neuropeptides, and proinflammatory cytokines, such as interleukin (IL) 2, IL-23, IL-31, interferon γ, and tumor necrosis factor α. Subsequently, the recruitment of inflammatory cells to the skin occurs as an exacerbated immune response, which translates into the unpleasant sensations [13,15,16].

Disruption of the Skin Barrier
In SSk, the defective epidermal barrier facilitates the penetration of irritants and allergens [7,15].In SSc, the disrupted barrier function was demonstrated by elevated pH level and increased transepidermal water loss [5].Also, there is abnormal sebum production and composition and perturbed microbiome, with a significant higher presence of Propionibacterium and lower bacterial diversity [5].

Classification
In 2023, Guerra-Tapia et al. [13] proposed a classification of SSc in two groups: primary and secondary.Primary sensitivity manifests in isolation or alongside any alopecia, such as androgenetic alopecia (AGA), telogen effluvium (TE), alopecia areata (AA), and cicatricial alopecias [13].On the other hand, secondary sensitivity is associated with a skin disease of the scalp, such as seborrheic dermatitis, psoriasis, atopic dermatitis, and contact eczema [13].
In our opinion, this classification is not helpful.Since the diagnosis of SSc as a pathological entity requires the exclusion of other conditions that may explain the symptoms, the inclusion of immune-mediated alopecia in the classification of primary sensitivity is incoherent.Most papers consider that SSc can co-exist with AGA and TE that are non-inflammatory disorders [2,4,6,8].

Clinical Manifestations and Trichodynia
The clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia that can lead to scratching impulse, with a negative impact on quality of life [4,9,10].Trichodynia is a painful sensation of the hair in a context of hair loss [17,18].It is also called as hair pain [19] and is considered as a symptom part of scalp sensitivity.This unpleasant sensation was described by Rebora et al. [17] in 1996, and it is usually reported by patients "as if the hairs were bent in the wrong way," more rarely as "stitches."Previous publications dating from 1946 to 1960 described similar uncomfortable scalp manifestations associated with hair loss [20,21].
Trichodynia is more frequent in women [23][24][25], possibly because they are more affected, seek for medical care more often, or have a higher pain perception [19,31].It is speculated that this condition is associated with perifollicular inflammation, increased expression of substance P in hair follicles, underlying psychiatric disorders, and nutritional deficiencies [19,25,27,32].It can affect the entire scalp or appear in localized areas, especially in the centroparietal region of the scalp, spontaneously or triggered by combing, drying, and use of accessories (hat, cap, barrettes) [2,13,19].
The skin of the SSc can be normal in appearance or present erythema (mild to intense).There are no specific trichoscopic features, but telangiectasias and dilated capillaries were reported [2].Scalp sensitivity is more common in patients with SSk and atopic dermatitis [3,8,10].Anxiety, emotional stress, depression, and other psychiatric conditions can appear as triggers or collateral damage of the scalp discomfort, affecting the quality of life [2,24].

Diagnosis
The diagnosis of SSc is guided by the anamnesis.Misery et al. [4] proposed a scale to evaluate the intensity of the discomfort, named 3S -Sensitive Scalp Scorethat consists in five questions with graduated answers from 0 to 4 (Table 2).The final score is obtained from the sum of the grades given to each type of sensation, classifying the scalp as slightly sensitive (up to 8), sensitive (from 9 to 11), or very sensitive (greater than or equal to 12).Ma et al. [9] proposed the 10Q questionnaire to evaluate symptoms (itching, prickling, tightness, pain, burning) related to triggers (sun, heat, air dryness, wind, humidity, exercises, stress, alcohol, hot beverages, spices).Those are useful tools in patient's follow-up.

Differential Diagnosis
It is essential to rule out dermatological conditions that can cause unpleasant symptoms as seborrheic dermatitis, psoriasis, atopic dermatitis, and contact eczema.

Trigeminal Trophic Syndrome
The trigeminal nerve, also named fifth cranial pair, has a sensitive motor function.It provides sensory innervation to the anterior region of the scalp, face, and auriculotemporal region, performed by the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches [33].Trigeminal trophic syndrome is a rare condition resulting from damage to the nerve due to a variety of causes, such as herpes zoster, trauma, neoplasms, infectious diseases, and iatrogenesis [34,35].This damage promotes intense itching, hypoesthesia, paresthesia, or pain in the territory of the affected branch, and may manifest in the scalp when branches V1 and/ or V3 are affected [34][35][36], as shown in Figure 1.The pruritus tends to be so intense that it can trigger a selfinduced ulcer in the affected area [35,37].The diagnosis of this syndrome involves a complete anamnesis to find the underlying cause, questioning the history of facial or cranial surgeries, previous cerebrovascular accident, and infectious diseases [37][38][39].

Postherpetic Neuralgia
Postherpetic neuralgia is the most common complication of herpes zoster and can occur in up to 20% of patients [38,40].It is manifested by chronic painful neuropathy in the territory of the affected nerve, which can last for months or years [41].The scalp is affected in cases of herpes zoster of V1 branch of the trigeminal nerve.In these cases, the patient has recurrent pain in the forehead and in the anterior region of the scalp, and may also manifest localized pruritus [38].The treatment of postherpetic neuralgia is challenging and demands multidisciplinary follow-up for a better management.

Management
There is lack of good-quality scientific studies to support treatment and still no specific guidelines for SSc management.We collected the recommendations and treatments published in the literature, all based on case series and experts' opinion, and organized them in 3 steps: scalp care, topical and systemic treatment.They are organized in alphabetical order in Figure 2 since there is no proven evidence-based superiority among them.Scalp care (step 1) addresses the barrier function of scalp and can be combined with topical and/or systemic medications.The history of previous treatments should also be considered, as well as the response to the proposed therapies.
Scalp Care Diminish or eliminate potential triggers in the patient's daily routine.Avoid scalp exfoliation [13], hair straighteners [42], and other chemical procedures that can cause irritative contact dermatitis.The scalp hygiene should be performed with non-irritating, amphoteric, or soft anionic surfactants, without any fragrance [13,15].There are personal care products with anti-inflammatory ingredients available on the market [43,44], or they can be personalized for each patient through compounding pharmacies.In the literature, hydrating products containing glycerin, hyaluronic acid, oils, or ceramides are suggested [13,15].For example, Guerra-Tapia et al. [13] recommended a transparent fluid gel formulation with sodium hyaluronate from 0.1% to 0.5%, glycerin 5%, hydroxypropyl methylcellulose 1.5%, Phenonip XB 0.6%, tween 20.1%, and purified water.Topical/Local Treatment Topical anesthetic or antipruritic agents are described as therapeutic choices but without description of specific substances [32].A combination of ketamine 5-10%, amitriptyline 5%, and lidocaine 5% compounded in a Lipoderm cream was published as effective to relieve cutaneous chronic pruritus in different body areas, even in the scalp [45].We recommend to be cautious when using topical anesthetic because of potential systemic toxicity.Capsaicin 0.025-1% is a substance derived from hot pepper, traditionally prescribed for chronic pruritus [46].Capsaicin initially activates the TRPV1, inducing pain and itch sensations, which are reduced during the continuous use of the medication [46].Pimecrolimus cream 10 mg/g once daily is a calcineurin inhibitor indicated as anti-inflammatory and immunomodulator to reduce TRPV1 activation in SSk [13,15,47].However, the use of creams and heavy lotions can be messy and not pleasant on scalp.Topical corticosteroids are commonly described as an option due to its anti-inflammatory effect, but the long-term use should be avoided as they may induce telangiectasias and skin atrophy [13,27,32].For patients already in use of topical minoxidil, consider switching to oral minoxidil if possible.
Some authors suggest benefit in use of mesotherapy with platelet-rich plasma because of its anti-inflammatory effect [48].Trimboli et al. [49] reported a single case of refractory trichodynia treated with botulinum toxin injections in the subcutaneous of the affected scalp.According to the authors, botulinum toxin can inhibit the release of neuropeptides, such as substance P, reducing the painful inflammatory activation of trichodynia [49].

Systemic Treatment
Patients with severe scalp sensitivity or refractory to previous therapies may benefit from oral treatment.Classic drugs in the management of chronic pain and psychodermatological disorders such as tricyclic antidepressants (amitriptyline, doxepin), selective serotoninnorepinephrine reuptake inhibitors (venlafaxine), and anticonvulsants (gabapentin and pregabalin) are used especially in cases of trichodynia [18,27,32,50].Although common practice, the use in SSc is not supported by clinical studies.Tricyclic antidepressants inhibit serotonin and norepinephrine reuptake: block histamine, muscarinic acetylcholine, and noradrenergic receptors.Due to its antihistamine-blocking activity, amitriptyline (10-25 mg/day) and doxepin (10-20 mg/day) can be effective in the management of chronic pruritus and scalp dysesthesia [34,50].Low dose of selective serotoninnorepinephrine reuptake inhibitors, as venlafaxine, may be helpful in cases with scalp discomfort due to psychogenic triggering factors [34].Gabapentin and pregabalin are anticonvulsants and act through inhibition of the neuropathic afferent pathway.They can be used to treat cutaneous neuropathic pain, itch, and cutaneous sensory syndromes [34].Gabapentin has an antipruritic effect, and its starting dose is 300 mg at bedtime that can be increased up to 2,400 mg/day.Pregabalin is also an option for neuropathic pruritus with a dose of 75 mg twice a day, to a maximum of 600 mg/day.Side effects include gastrointestinal alterations, peripheral edema, and weight gain [50].
A short cycle of oral corticosteroids was described in the treatment of SSk.According to authors, 2 weeks' therapy is usually sufficient, with a dose of 0.5 mg/kg/day during the first week and gradual reduction during the second [2].In recent years, low-dose naltrexone became an option in the management of symptomatic disorders of the scalp, such as cicatricial alopecia, trichotillomania, AA [51,52].Naltrexone is a competitive opioid receptor antagonist approved by the FDA since 1984 for the treatment of opioid dependence [51,53].Treatment with doses lower than 5 mg/day has a paradoxical mechanism with analgesia and anti-inflammatory effect, reducing scalp pruritus [51,52,54].Although there are still no specific guidelines, it is suggested nocturnal usage with dose ranges from 1 to 5 mg/day, starting at 3 mg/day and gradually increasing to 5 mg/dayif necessary [52].Lowdose naltrexone has fewer side effects than the usual dose, but insomnia and vivid dreams are reported [51,52].It should not be used during pregnancy or in patients with opioid dependence [51].A successful case report described the use of propranolol 10 mg/day prescribed to a 76-year-old patient with hair loss, trichodynia, and a history of depression.The medication was administered for 2 months with improvement of symptoms after 5 days of use.However, there was a recurrence of the condition 6 months after drug discontinuation [55].

Conclusion
SSc is part of the SSk syndrome and has its particularities.It may be associated with hair disorders and skin diseases of the scalp.It is a frequent discomfort in the general population, which can have a great impact on the patient quality of life, depending on the intensity of unpleasant symptoms.There are still no specific recommendations for the management of this condition, and further studies are needed to elucidate the etiopathogenesis and treatment of the disease.

Fig. 2 .
Fig. 2. Review of treatments for SSc proposed in literature divided into three main pillars: scalp care, topical/local and systemic treatment (organized in alphabetical order).

Table 1 .
Summary of epidemiological studies regarding SSc