Dandruff, medically termed pityriasis capitis, is a common scalp condition characterized by flaking of the skin. While often considered a cosmetic issue, emerging research is uncovering the complex interplay of microorganisms, host factors, and inflammatory responses that contribute to its development. This article delves into the microscopic aspects of dandruff, exploring the microorganisms involved, the structural changes in the scalp, and the underlying mechanisms that lead to the characteristic itching and scaling.
Seborrheic dermatitis (SD) and dandruff are considered to be on a continuous spectrum of the same disease. Dandruff is typically restricted to the scalp, involving itchy, flaking skin without visible inflammation. SD, on the other hand, can affect the scalp, face, retro-auricular area, and upper chest, causing flaking, scaling, inflammation, and pruritus. It is estimated that SD and dandruff combined affect half of the adult population.
As the skin layers continually replace themselves, cells are pushed outward where they die and flake off. For most individuals, these flakes of skin are too small to be visible. However, certain conditions cause cell turnover to be unusually rapid, especially in the scalp. It is hypothesized that for people with dandruff, skin cells may mature and be shed in two to seven days, as opposed to around a month in people without dandruff.
For a long time, studies on dandruff predominantly focused on fungi, particularly the Malassezia species, which are major fungi colonizing the human scalp and the dominant members of the cutaneous fungal microbiome. Older literature cites the fungus Malassezia furfur (previously known as Pityrosporum ovale) as the cause of dandruff. While this species does occur naturally on the skin surface of people both with and without dandruff, in 2007, it was discovered that the responsible agent is a scalp specific fungus, Malassezia globosa, that metabolizes triglycerides present in sebum by the expression of lipase, resulting in the lipid byproduct oleic acid.
Of the 14 known cultured species of Malassezia, the most clinically significant species are M. restricta and M. globosa. These lipophilic yeasts are found mainly on seborrheic regions of the body. Studies have detected Malassezia on the scalp of dandruff patients, and higher numbers of Malassezia (M. globosa and M. restricta) correlate with SD appearance/severity.
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However, another microorganism community composed of bacteria also inhabits the human scalp and includes facultative anaerobic bacteria, such as P. Using 454 pyrosequencing of the microbiome on scalp dandruff, eleven bacterial phyla were detected, but most sequences were assigned to two bacterial phyla: Actinobacteria (64.9%) and Firmicutes (32.5%). Of the 123 identified genera, Propionibacterium (63.3%, Actinobacteria) and Staphylococcus (32.4%, Firmicutes) comprised more than 95% of the total sequences. A total of 99.7% of the Propionibacterium belonged to P. acne, and 94.9% of the Staphylococcus were Staphylococcus spp (including S. epidermidis, S. capitis and S. It was found that Propionibacterium decreased from 70.8% to 50.2% in the dandruff group, whereas Staphylococcus increased from 26.0% to 43.5%. Redundancy analysis (RDA) identified 33 genera related to severity of dandruff including Staphylococcus showed a significant positive correlation with dandruff. In contrast, only two genera (Propionibacterium and Labrys) showed a significant negative correlation with dandruff.
Dandruff scale is a cluster of corneocytes, which have retained a large degree of cohesion with one another and detach as such from the surface of the stratum corneum. A corneocyte is a protein complex that is made of tiny threads of keratin in an organised matrix. The size and abundance of scales are heterogeneous from one site to another and over time. Parakeratotic cells often make up part of dandruff.
Scalp pruritus is a common and distressing symptom. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. It is most commonly associated with seborrheic dermatitis and psoriasis but appears often without any noticeable skin lesion or obvious diagnosis. It is considered a diagnostically and therapeutically challenging situation particularly when no other body part itches and no detectable lesion is seen. Although scalp itch is considered common, there is a paucity of data published on its prevalence . In a study conducted on a quantitatively representative sample of the French population, scalp itching was reported in 25% of the population .
Scalp pruritus can arise from a variety of conditions including dermatologic, systemic, neurologic and psychogenic diseases. Among patients with psychogenic pruritus, the most commonly affected sites are scalp and face. The most common presentation of scalp pruritus occurs in the setting of seborrheic dermatitis. Pathogenesis of seborrheic dermatitis is complex and appears to result from interactions among scalp skin, sebaceous secretions, Malassezia fungi, and the cutaneous immune system. Kerr et al. suggested an association between the subjective perception of itch in the scalp of seborrheic dermatitis patients and the level of histamine in the skin. They reported also that the scalp histamine level in subjects with seborrheic dermatitis was more than twice that in those without it. Treatment with a commercial potentiated zinc pyrithione shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. A recent large survey of 195 psoriatic patients showed that 58% suffer from scalp pruritus. Another survey in moderate to severe chronic-plaque psoriasis revealed regional variations in the sites of pruritus; the most affected anatomical site was the scalp (50%). Scalp itching is commonly encountered in patients with lichen planopilaris when inflammation is present. Scalp pruritus is seen in approximately 70% of patients. Neuropathic itch in scalp can be seen in association with diabetes mellitus, and herpes zoster. Scribner observed several patients whose primary complaint of pruritus confined to the scalp proved to be caused by unsuspected diabetes. Post herpetic neuralgia (PHN) has been historically associated with pain. However data emerged that PHN also induces Post herpetic itch (PHI). A large epidemiological study reported PHI in roughly half of PHN patients. PHI can coexist with PHN or occur alone. In a patient with PHI on the scalp, quantitation of PGP 9.5-immunoreactive epidermal nerves demonstrated loss of 96% of PGP 9.5 stained epidermal innervation in the itchy area. Concomitantly, quantitative sensory testing indicated severe damage to most sensory modalities except itch. Possible mechanisms include selective preservation of peripheral itch-fibers from neighboring unaffected dermatomes, imbalance between excitation and inhibition of second-order sensory neurons, and/or electrical hyperactivity of hypo-afferented central itch specific neurons. Oaklander has suggested that the excessive scratching observed in some patients with PHI may be due to a reduced sensation of pain. Normally, the act of scratching to relieve itch elicits mild pain, which provides a protective negative feedback to halt further scratching. In PHI, scratching the affected skin area elicits no pain, so that scratching persists unabated, sometimes to the point of severe skin damage. Ross et al. recently demonstrated the existence of itch inhibitory interneurons within the dorsal horn. Bhlhb5 mutant mice lacking these interneurons had persistent itch. Glutamate is one of the major excitatory neurotransmitters in the spinal cord and may have a role in these interneurons. Sensitive skin is characterized by subjective complaints of discomfort without predictable classical visible signs of irritation and without an immunologic response. It was found that 36% of 400 subjects in 2 hospitals declared that they had sensitive skin on scalp. Further epidemiological studies revealed that 44% and 32% subjects declared suffering from sensitive scalp. Itching affects about 60% of subjects with sensitive scalp.
The pathogenesis of scalp pruritus has rarely been investigated. The sensory innervation of the scalp conducted through branches from the trigeminal nerve, cervical plexus and dorsal rami of the cervical nerves. The hair follicle (HF) is highly innervated with four types of specific nerve endings. These are: free nerve endings (nociceptors), lanceolate nerve endings (acceleration detectors), Merkel nerve endings (pressure detectors), and pilo-Ruffini corpuscles (tension detectors). The free nerve endings innervating the HF are from A-delta (thinly myelinated) or C fibers (unmyelinated) that emerge from the superficial nerve plexus. These nerves terminate as free nerve endings in the connective tissue between the sebaceous gland and HF. Furthermore, HF development and cycling do affect the HF innervations. Peters et al. showed that cutaneous and follicular neuropeptide-containing NFs express major hair-cycle-associated changes . Initially, epidermal innervation is very dense, while it decreases and gains neuropeptide expression after penetration of HFs through the epidermis.
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In addition to HF, the scalp has abundant blood vessels more than in any other body region. There are also cyclic changes of perifollicular vascularization. Yano et al. found a significant increase in perifollicular vascularization during the anagen phase of HF, followed by regression of angiogenic blood vessels during the catagen and telogen phases. Pruritus involves different classes of cutaneous unmyelinated, slowly transmitting, sensory C-NFs that are distributed in the epidermis and papillary dermis. They are of two types; mechano-insensitive that are activated by histamine, and mechano--sensitive that cause pruritus with burning when induced activated by cowhage spicules (Mucuna pruriens). Two systematic quantifications of epidermal NF density in multiple body sites revealed that scalp epidermal NF density was comparable to the back, but less than the cheek, neck and distal limbs. This variability in NF density may explain the topographical distribution of sensory thresholds in human skin to temperature as well as itch and pain. Informative data, namely distribution of C-fibers at various body sites, is lacking. Although the scalp is considered extremely itchy in many cutaneous inflammatory diseases and as mentioned above highly innervated, experimental itch studies in humans were not able to demonstrate lower itch thresholds. Rukwied et al. reported that forearm was more itch-sensitive than the scalp when investigated by histamine intradermal microdialysis, whereas topical application of histamine demonstrated that scalp was more itch-sensitive than the forearm skin. Shelly and Arthur had also demonstrated differences in itch perception among various areas of the body by the insertion of cowhage spicules, which activate Proteinase activating receptor 2 (PAR-2), an important non histaminergic itch pathway (see below). In their studies, the scalp showed no response to cowhage spicules. Furthermore, hand and ankle were more sensitive to electrically evoked itch as compared to head and neck. These data corroborate with Essick et al. findings who studied the thresholds for detection of cooling, warming, cold pain and heat pain. They found that the scalp was notably less sensitive to thermal stimulation compared to other body areas, regardless of specific sensation considered. Whether these differences in thermal sensitivity between body sites is related to spatial variation in the density of thermal receptors or to differences in central neural processing is a matter of debate.
Histamine is the prototype of endogenous itch mediator secreted from MCs and can induce pruritus via H1 and H4 receptors on NFs, whereas H3 receptors appear to be involved in the suppression of pruritus. MC can induce pruritus directly also through the release of other mediators such as chymase, tryptase and cytokines. MC also secrete neurotrophins such as nerve growth factor (NGF) that contribute to hyperplasia of NFs in chronic pruritus forms, as has been observed in Atopic dermatitis (AD). MCs function also as hair cycle regulators and are involved in the control of HF regression in murine system. MC number, degranulation activity, histochemical staining characteristics, histamine/heparin skin content, and physical MC-NF contacts all fluctuate significantly during synchronized HF cycling in rodent skin. MC density in scalp skin does not differ significantly from that in forearm skin.
PAR-2 is a G-protein coupled receptor. PAR-2 plays major role in mediating chronic pruritus. During neurogenic inflammation, various endogenous serine proteases such as trypsins from keratinocytes and tryptase from MCs activate PAR-2 on sensory nerve ending to release calcitonin gene-related peptide (CGRP) and substance P (SP). PAR-2 signaling also stimulates the release of neuropeptides from central nerve endings thereby activating CGRP receptor and SP receptor (NK1R) to transmit itch responses to the central nervous system. Recently, it was shown that Cathepsin S which is an endogenous cystein protease evokes itch and activates PAR-2 and 4. Exogenous activators of PAR2 may be serine proteinases generated by bacteria, fungi, and house dust mites. PAR-2 interacts synergistically with transient receptor potential vanilloid-type 1 (TRPV1), thereby amplifying itch sensation (see below). In the skin, PAR-2 is expressed by almost all cell types including keratinocytes, HF, sensory neurons, and MCs. In human HF, PAR-2 is confined to the Inner root sheath (IRS). PAR-2 activation is likely to be involved in pruritus of AD. In addition, skin exposure to exogenous microbial proteases could also induce itch and inflammation via PAR-2. This could explain why staph folliculitis in the scalp is extremely itchy.
TRPV1 receptor is activated by capsaicin, the key ingredient of hot chilli peppers. In addition to capsaicin, TRPV1 can also be activated by heat, acidosis and endogenous endovanilloids such as arachidonic acid derivatives, lipid peroxidation metabolites, and endocannabinoids. When TRPV1 is activated, it causes burning pain, itching and heat sensation, which is suppressed by continuous activation. TRPV1-expressing neurons are required for the behavioral responses to several different pruritic compounds including histamine, serotonin, and endothelin-1. TRPV1-expressing neurons have multiple intracellular mechanisms that generate or mediate itch. TRPV1 is highly expressed on sensory NFs, epidermal keratinocytes, HFs, dermal blood vessels, MCs, sebaceous glands and eccrine sweat glands. In human HF, TRPV1 is confined mainly to the Outer root sheath (ORS) and hair matrix. TRPV1 has a significant role in human hair growth control. In organ culture, TRPV1 activation by capsaicin resulted in hair shaft elongation, suppression of proliferation, induction of apoptosis, premature HF regression (catagen), and up-regulation of intrafollicular transforming growth factor-B2. Cultured human ORS keratinocytes also expressed functional TRPV1, whose stimulation inhibits proliferation, induces apoptosis, up-regulate known endogenous hair growth inhibitors (interleukin-1B, transforming growth factor-B2), and down-regulate known hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor). In rat skin, hair growth retardation, along with alopecia and a decrease in hair shaft thickness, follows as a consequence of capsaicin-induced sensory denervation. Pirt gene was recently identified as a regulator of TRPV1, in both histaminergic and nonhistaminergic itch. Tacrolimus has been reported to have anti-itch property, unrelated to its anti inflammatory property. This was explained possibly by a desensitization of TRPV1 and calcium currents through the phosphatidylinositol 4,5-bisphosphate regulation pathway. It would be of great interest to examine the role of TRPV1 receptor and its ligands in itchy scalp. Another thermosensitive Transient Receptor Potential channel which has been shown to have a role in itch in mice is TRPV3. TRPV3 is abundantly expressed in keratinocytes and scalp HF, mainly the ORS. Activation of TRPV3 shown recently to inhibit human hair growth.
Mrgpr family can be activated directly by peptides with common C-terminal motifs like RFamide, -RYamide, -RYG or -RLamide, neuropeptide AF, γ2-melanocyte-stimulating hormone, bovine adrenal medulla8-22 peptide [BAM8-22] and chloroquine. Recently, direct evidence proved the involvement of some of these peptides in itch sensation. Mouse MrgprA3 and MrgprC11 act as itch receptors in the skin for the pruritogens chloroquine, and bovine adrenal medulla 8-22 peptide (BAM8-22) and synthetic peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) respectively. In human MrgprXs expression was detected exclusively in DRG neurons.
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Opioids and their receptors in the skin comprise part of the endogenous opioid system. It includes three opioid receptors: Mu (MOR), Delta (DOR) and Kappa (KOR), and the opioid peptides, such as enkephalins, endorphins, dynorphins and endomorphins. It is widely accepted that KOR signaling suppresses itch, while MOR signaling can stimulate itch. MOR seems to be important in chronic forms of pruritus, while KOR agonists are important in acute itching. Neuronal communication between pain- and itch-transmitting neurons underlies the role of opioids in pruritus. Many painful stimuli shown to inhibit itch by activating specific nociceptive pathways.
Diagnosis of SD is typically made by history and physical examination. In rare cases, a skin biopsy is needed for differential diagnosis. Histologically, the development of SD can be divided into two stages. In the acute and sub-acute stages, SD shows superficial perivascular and perifollicular inflammatory infiltrates, composed mainly of lymphocytes and histiocytes in association with spongiosis and psoriasiform hyperplasia, and can be coupled with parakeratosis around follicular opening (âshoulder parakeratosisâ). Neutrophils can also be found in the scale crust at the margins of follicular ostia. On the other hand, in chronic lesions, marked psoriasiform hyperplasia and parakeratosis can be present with dilation of the venules of surface plexus which resembles psoriasis. Dandruff shows many common features as SD in histology, such as epidermal hyperplasia, parakeratosis, and Malassezia yeasts surrounding the parakeratotic cells. Whereas inflammatory cells such as lymphocytes and NK cells may be present in great numbers in SD, dandruff shows subtle neutrophil infiltration or no infiltration.
Treatment of SD and dandruff focuses on clearing signs of the disease; ameliorating associated symptoms, especially pruritus; and maintaining remission with long-term therapy. Because the main underlying pathogenic mechanisms involve Malassezia proliferation and local skin irritation and inflammation, the most common treatment is topical antifungal and anti-inflammatory agents. Other widely used therapies are coal tar, lithium gluconate/ succinate and phototherapy. New therapies have also emerged including immune modulators such as topical calcineurin inhibitors, and metronidazole, but their efficacy remains controversial. Alternative therapies have been reported as well, such as tea tree oil. Some factors to be considered before selecting a treatment include efficacy, side effects, ease of use/compliance, and age of the patient.
Antifungal treatments including piroctone olamine, ketoconazole (Sebizole), zinc pyrithione, and selenium disulfide (Selsun Blue) have been found to be effective. Ketoconazole appears to have a longer duration of effect. Ketoconazole is a broad-spectrum antimycotic agent that is active against Candida and M. furfur. Other than zinc pyrithione, the most common anti-dandruff actives (outside the US) and part of many cosmetic shampoos, are piroctone olamine and climbazole.
tags: #itchy #scalp #dandruff #microscope #analysis
