hair and scalp changes in cutaneous and systemic lupus 2018

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<p>REVIEW ARTICLE</p><p>Hair and Scalp Changes in Cutaneous and Systemic Lupus</p><p>Erythematosus</p><p>Siriorn Udompanich1 • Kumutnart Chanprapaph1 • Poonkiat Suchonwanit1</p><p>� Springer International Publishing AG, part of Springer Nature 2018</p><p>Abstract Cutaneous and systemic lupus erythematosus</p><p>(SLE) commonly involves the hair and scalp. Alopecia can</p><p>result from direct activity of disease on the scalp or from</p><p>the state of physical stress in the form of telogen effluvium.</p><p>Discoid lupus erythematosus and lupus panniculitis/pro-</p><p>fundus are known to cause scarring alopecia, while accu-</p><p>mulation of recent studies has shown that non-scarring</p><p>alopecia in SLE may have different subtypes, comprising</p><p>lupus erythematosus-specific and lupus erythematosus-</p><p>nonspecific changes on histology. This review aims to</p><p>summarize the clinical pattern, trichoscopic, histopatho-</p><p>logical, and direct immunofluorescence features of differ-</p><p>ent types of alopecia in cutaneous and systemic lupus</p><p>erythematosus, as well as exploring their relationship with</p><p>SLE disease activity.</p><p>Key Points</p><p>Alopecia is among one of the most common</p><p>cutaneous involvements in systemic lupus</p><p>erythematosus (SLE).</p><p>Alopecia in SLE comprises different subtypes.</p><p>Recent studies have introduced new terms such as</p><p>diffuse and patchy alopecia in SLE. These conditions</p><p>have lupus erythematosus-specific changes on</p><p>histology and are reversible after SLE treatment.</p><p>Physicians who encounter patients should always</p><p>spare some time to examine the hair and scalp as</p><p>they can provide valuable clues for the diagnosis and</p><p>monitoring of SLE.</p><p>1 Introduction</p><p>Systemic lupus erythematosus (SLE) affects various organs</p><p>in the body, with cutaneous involvement being the second</p><p>most common clinical manifestation after joint inflamma-</p><p>tion [1]. The active role of dermatologists in detecting,</p><p>monitoring, and managing skin lesions can be challenging</p><p>given the heterogeneous nature of the disease. Neverthe-</p><p>less, details on clinical, trichoscopic, histopathological, and</p><p>direct immunofluorescence (DIF) features of different</p><p>forms of cutaneous lupus erythematosus (LE), along with</p><p>their risks of systemic involvement, have been collectively</p><p>studied and implemented daily in clinical practice.</p><p>On the contrary, hair and scalp involvement in cuta-</p><p>neous and systemic LE may have been overlooked, despite</p><p>the fact that the prevalence of alopecia ranges from 17.3 to</p><p>& Poonkiat Suchonwanit</p><p>poonkiat@hotmail.com</p><p>1 Division of Dermatology, Faculty of Medicine, Ramathibodi</p><p>Hospital, Mahidol University, 270 Rama VI Road,</p><p>Ratchathewi, Bangkok 10400, Thailand</p><p>Am J Clin Dermatol</p><p>https://doi.org/10.1007/s40257-018-0363-8</p><p>http://orcid.org/0000-0001-9723-0563</p><p>http://crossmark.crossref.org/dialog/?doi=10.1007/s40257-018-0363-8&amp;domain=pdf</p><p>http://crossmark.crossref.org/dialog/?doi=10.1007/s40257-018-0363-8&amp;domain=pdf</p><p>https://doi.org/10.1007/s40257-018-0363-8</p><p>85.2% of SLE patients [2–4]. Furthermore, the impact on</p><p>their quality of life can be overwhelming, as evidenced by</p><p>the statistically significant lower Dermatology Life Quality</p><p>Index (DLQI) score [5].</p><p>In this review, we aim to provide a comprehensive</p><p>summary of different types of hair and scalp manifestations</p><p>in cutaneous and systemic LE in the hope of improving our</p><p>understanding and, consequently, patient management.</p><p>Current diagnostic criteria, classification, and scoring sys-</p><p>tems for cutaneous and systemic LE, especially regarding</p><p>the incorporation of alopecia, are discussed, followed by</p><p>details of the clinical presentation, differential diagnosis,</p><p>relationship with SLE, and treatment and prognosis of each</p><p>type of scarring and non-scarring condition. Finally, mis-</p><p>cellaneous conditions that are linked to SLE are discussed,</p><p>thus providing thorough information on all pathologies that</p><p>can occur on the scalp.</p><p>2 Diagnostic Criteria, Classifications, Scoring</p><p>Systems, and the Incorporation of Alopecia</p><p>Alopecia is a common, well-recognized sign of LE, as</p><p>evidenced by its integration into the most widely accepted</p><p>classification and scoring systems for cutaneous and sys-</p><p>temic LE. For SLE, the original diagnostic criteria, by the</p><p>American College of Rheumatology (ACR), were created</p><p>in 1982 and revised in 1997 [6, 7]. In 2012, the Systemic</p><p>Lupus International Collaborating Clinics (SLICC) pro-</p><p>posed a new criteria that proved to be more sensitive in</p><p>clinical practice [8]. For cutaneous involvement, the</p><p>SLICC has incorporated acute cutaneous lupus, chronic</p><p>cutaneous lupus, and oral or nasal ulcers into the criteria, as</p><p>well as a separate section entitled non-scarring alopecia</p><p>that defines as diffuse, thinning or hair fragility with visible</p><p>broken hairs, in the absence of other causes such as</p><p>alopecia areata (AA), drugs, iron deficiency, and andro-</p><p>genic alopecia.</p><p>Cutaneous manifestation of LE can occur as part of SLE</p><p>or as an isolated disease confined to the skin. From the</p><p>dermatologists’ perspective, cutaneous LE can be divided</p><p>into histopathology-specific and non-specific lesions [9].</p><p>Despite not possessing features of LE on histology, the risk</p><p>of systemic disease for non-specific LE is relatively high</p><p>[10]. Following this review, we classified hair involvement</p><p>in the same manner by considering a condition as LE-</p><p>specific when LE and interphase changes have been</p><p>detected on histology, or when the condition has been</p><p>described exclusively in LE patients. Table 1 shows our</p><p>proposed classification for alopecia in SLE, while Table 2</p><p>provides a summarized comparison.</p><p>Various scoring systems for monitoring disease activity</p><p>include alopecia as one of the indicators of SLE</p><p>exacerbations, although they are primarily used in research</p><p>studies. An example is the Systemic Lupus Erythematosus</p><p>Disease Activity Index (SLEDAI), which gives alopecia a</p><p>score of 2 and describes the condition as abnormal, patchy,</p><p>or diffuse loss of hair [11]. The British Isles Lupus Activity</p><p>Group (BILAG) index also mentions alopecia in their</p><p>severity score, dividing alopecia into mild and severe [12].</p><p>Nevertheless, the association between alopecia and SLE</p><p>activity has not been fully validated, given the wide range</p><p>of abnormal clinical and laboratory data in SLE. It is</p><p>possible that different types and extent of alopecia have</p><p>different degrees of correlation, with several studies</p><p>attempting to prove this relationship in the past. In a large</p><p>cross-sectional study of 122 SLE patients, no correlation</p><p>was found between alopecia and SLEDAI [4]. In contrast, a</p><p>study evaluating 74 SLE patients found a statistically sig-</p><p>nificant association between alopecia and other LE cuta-</p><p>neous manifestations, conjunctivitis, and Raynaud’s</p><p>phenomenon. However, there was no association with</p><p>systemic disease manifestations such as arthritis or renal</p><p>involvement, or with laboratory variables such as anti-</p><p>deoxyribonucleic acid antibodies, complement component</p><p>3 (C3), or erythrocyte sedimentation rate (ESR) [13]. These</p><p>findings were derived from cross-sectional studies and</p><p>should be interpreted with caution as timing between onset</p><p>of alopecia and disease severity assessment was obscure.</p><p>Future prospective cohort studies may help justify the</p><p>relationship. Meanwhile, studies on specific types of</p><p>alopecia have provided information on the status of</p><p>patients included in the study, giving an approximate</p><p>estimation of whether or not the pattern correlates with</p><p>disease exacerbation.</p><p>3 Scarring Alopecia in Systemic Lupus</p><p>Erythematosus (SLE)</p><p>Scarring or cicatricial alopecia refers to hair loss conditions</p><p>in which the destruction of follicular stem cells leads to</p><p>permanent alopecia. In patients with SLE, discoid lupus</p><p>erythematosus (DLE) and lupus panniculitis/profundus are</p><p>well known to cause scarring alopecia.</p><p>3.1 Discoid Lupus Erythematosus</p><p>3.1.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and Direct Immunofluorescence</p><p>(DIF) Features</p><p>DLE is classified as chronic cutaneous LE. The most</p><p>common locations</p><p>are on the face, ears and scalp. Up to</p><p>60% of patients with DLE have scalp involvement, one-</p><p>third of whom suffer from scarring alopecia, which can</p><p>S. Udompanich et al.</p><p>greatly impact their quality of life [10]. Classically, DLE is</p><p>a well-demarcated erythematous scaly plaque with epi-</p><p>dermal atrophy, follicular plugging, central hypopigmen-</p><p>tation and peripheral hyperpigmentation in dark-skinned</p><p>individuals. The lesion progressively develops, starting</p><p>from an early non-scarring to late scarring alopecic patch,</p><p>and may be pruritic, tender, or asymptomatic (Fig. 1a).</p><p>Follicular red dots are the most characteristic sign on tri-</p><p>choscopy. Additional trichoscopic findings are large yellow</p><p>dots, thick arborizing vessels, scattered dark-brown dis-</p><p>coloration, and blue-gray dots forming a speckled pattern</p><p>(Fig. 1b) [14–16]. On histopathology, basal vacuolization</p><p>of the epidermis and follicular epithelium (Fig. 1c),</p><p>perieccrine and perivascular lymphocytic infiltration, and</p><p>increased dermal mucin are typically seen. These findings</p><p>are specific to LE. On DIF, granular deposits of mainly</p><p>immunoglobulin (Ig) G and C3 along the dermoepidermal</p><p>junction (DEJ) and follicular epithelium are noted</p><p>(Fig. 1d). However, even in clear-cut DLE cases, DIF can</p><p>be negative [17].</p><p>3.1.2 Differential Diagnosis</p><p>DLE on the scalp must be differentiated from other con-</p><p>ditions that can cause scarring alopecia. Lichen planopi-</p><p>laris (LPP), a form of lichen planus on the scalp, also</p><p>occurs more often in women and presents with perifollic-</p><p>ular erythema, scale, and scarring. Variants of LPP include</p><p>frontal fibrosing alopecia, a condition that affects the</p><p>anterior hairline of postmenopausal women, and Graham–</p><p>Little syndrome, in which scarring alopecia of the scalp is</p><p>accompanied by non-scarring alopecia of the axillary and</p><p>pubic regions and spinous follicular papules on the body</p><p>[18, 19]. Trichoscopic examination reveals discrete white</p><p>dots, a distinguishing sign of LPP that signifies the loss of</p><p>melanin over perifollicular fibrotic tracts. The process of</p><p>fibrosis is relatively more diffuse in DLE, resulting in an</p><p>appearance of milky red or white areas between the folli-</p><p>cles [20]. Blue-gray dots in a target pattern are found in</p><p>LPP, while a speckled pattern suggests DLE [16]. Never-</p><p>theless, the diagnosis of LPP can sometimes be made on</p><p>clinical grounds alone, however confirmatory histology</p><p>sections showing lichenoid infiltration along the follicular</p><p>epithelium or colloid bodies may be required in case of</p><p>doubt. Other differential diagnoses in the scarring alopecia</p><p>group are central centrifugal cicatricial alopecia, Brocq’s</p><p>alopecia, and alopecic patches from morphea. At times,</p><p>early DLE may share similar clinical features with AA as</p><p>both conditions are localized and well-defined. Patchy,</p><p>non-scarring alopecia in SLE, a form of hair loss classified</p><p>as LE-specific and providing similar histopathological and</p><p>DIF features as DLE, should also be included in the dif-</p><p>ferential diagnosis.</p><p>3.1.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>The risk of SLE in patients with DLE is relatively small</p><p>(approximately 5–15%) [21–24], but may be higher when</p><p>the lesions are below the head and neck, or when periun-</p><p>gual telangiectasias, arthritis, or abnormal laboratory</p><p>results are noted, including high titer antinuclear antibodies</p><p>(ANA), leukopenia, anemia, and persistently elevated ESR</p><p>rate [25]. Conversely, among SLE patients, 11.2–17.6%</p><p>developed DLE [26, 27]. The presence of DLE has been</p><p>inconclusively linked with a more benign systemic disease,</p><p>having been associated with a significantly decreased risk</p><p>of arthritis and pleuritis in one cohort and a lower risk of</p><p>end-stage renal disease in the other [26, 27].</p><p>3.1.4 Treatment and Prognosis</p><p>With DLE, prompt diagnosis and treatment are the key, and</p><p>physicians should bear in mind that once the scarring</p><p>process has fully involved the hair follicles, hair loss is</p><p>permanent. Photoprotection with sunscreens, and smoking</p><p>cessation, may play a role in the prevention of new lesions</p><p>[28, 29]. When detected early, DLE lesions respond well to</p><p>oral antimalarial medication and potent topical, oral, and</p><p>intralesional corticosteroids. Topical calcineurin inhibitors</p><p>are also considered first-line treatment, especially on the</p><p>area of thinned skin or where skin atrophy from the disease</p><p>is already evident, although longer treatment duration may</p><p>Table 1 Proposed classification for alopecia in SLE</p><p>LE-specific (alopecia as a direct result of LE activity on the scalp)</p><p>Scarring:</p><p>Discoid lupus erythematosus</p><p>Classic lupus panniculitis/profundus</p><p>Non-scarring:</p><p>Diffuse non-scarring alopecia in SLE</p><p>Patchy, non-scarring alopecia in SLE</p><p>Lupus hair</p><p>Linear and annular lupus panniculitis of the scalp</p><p>LE nonspecific</p><p>Telogen effluvium</p><p>Anagen effluvium</p><p>Alopecia areata</p><p>Secondary cutaneous lesions related to SLE:</p><p>Alopecia mucinosa</p><p>Basaloid follicular hamartoma</p><p>Dystrophic calcinosis cutis on the scalp</p><p>Hair shaft abnormalities related to SLE</p><p>LE lupus erythematosus, SLE systemic lupus erythematosus</p><p>Hair and scalp changes in cutaneous and systemic 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Udompanich et al.</p><p>be required when compared with topical corticosteroids</p><p>[30]. Other treatment modalities with limited supporting</p><p>evidence include methotrexate, topical and systemic reti-</p><p>noids, dapsone, thalidomide, and mycophenolate mofetil.</p><p>Severe cases may benefit from rituximab, ustekinumab,</p><p>and intravenous IG (IVIG). Potential novel therapies,</p><p>including various biologics, are currently under investiga-</p><p>tion [30].</p><p>3.2 Lupus Panniculitis/Lupus Profundus</p><p>3.2.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and DIF Features</p><p>Lupus panniculitis is chronic inflammation of subcutaneous</p><p>tissue caused by LE. This rare type of chronic cutaneous</p><p>LE only features in 2–3% of the group of patients with</p><p>lupus panniculitis. Overlying DLE is found in approxi-</p><p>mately one-third of patients, and together the lesion is</p><p>termed lupus profundus [31]. Lupus panniculitis/profundus</p><p>occurs predominantly in young women. The tender indu-</p><p>rated erythematous subcutaneous nodules or plaques</p><p>appear most frequently on the face, arms, hips, and trunks</p><p>(Fig. 2a). Trichoscopic features have not been reported in</p><p>previous publications. Regarding our experience, large</p><p>yellow dots, black dots, short vellus hairs, thick arborizing</p><p>vessels, and diffuse erythema on the interfollicular areas</p><p>can be observed under trichoscopy. Without proper man-</p><p>agement, the lesion can progressively become atrophic and</p><p>disfiguring. Scalp involvement was reported in up to 16.4%</p><p>of cases, typically resulting in scarring alopecia [32, 33].</p><p>An unusual presentation was reported in the form of scle-</p><p>rodermic linear lupus panniculitis [34]. As opposed to</p><p>classic lupus panniculitis lesions, the invasion of subcuta-</p><p>neous tissue of the scalp by LE may manifest as linear,</p><p>arcuate, or annular patches along the suspected Blaschko’s</p><p>lines of the scalp. This condition is termed linear lupus</p><p>panniculitis of the scalp (LLPS) or linear and annular lupus</p><p>panniculitis of the scalp (LALPS). In contrast to classic</p><p>lupus panniculitis, the alopecia is non-scarring and rever-</p><p>sible. Further information on this condition is discussed</p><p>later in this review.</p><p>Pathology section of lupus panniculitis shows lobular</p><p>panniculitis with hyaline necrosis and predominant lym-</p><p>phoplasmacytic infiltration, occasionally forming lympho-</p><p>cytic aggregation and lymphoid follicles (Fig. 2b) [35].</p><p>Furthermore, the presence of overlying skin changes</p><p>resembling DLE can aid the diagnosis. In a retrospective</p><p>review of biopsy specimens, thickening of the basement</p><p>membrane, basal vacuolization, and pigment incontinence</p><p>were evident, even in cases that displayed no epithelial</p><p>changes clinically [32]. A majority of lesions stain positive</p><p>on DIF, with granular deposition of IgM and C3 at the 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/p><p>d</p><p>ro</p><p>g</p><p>en</p><p>et</p><p>ic</p><p>al</p><p>o</p><p>p</p><p>ec</p><p>ia</p><p>,</p><p>d</p><p>if</p><p>fu</p><p>se</p><p>A</p><p>A</p><p>A</p><p>A</p><p>,</p><p>sy</p><p>p</p><p>h</p><p>il</p><p>it</p><p>ic</p><p>al</p><p>o</p><p>p</p><p>ec</p><p>ia</p><p>,</p><p>p</p><p>so</p><p>ri</p><p>at</p><p>ic</p><p>al</p><p>o</p><p>p</p><p>ec</p><p>ia</p><p>H</p><p>ai</p><p>r</p><p>ab</p><p>n</p><p>o</p><p>rm</p><p>al</p><p>it</p><p>ie</p><p>s</p><p>fo</p><p>u</p><p>n</p><p>d</p><p>in</p><p>h</p><p>y</p><p>p</p><p>o</p><p>th</p><p>y</p><p>ro</p><p>id</p><p>is</p><p>m</p><p>A</p><p>A</p><p>,</p><p>m</p><p>o</p><p>rp</p><p>h</p><p>ea</p><p>(e</p><p>n</p><p>co</p><p>u</p><p>p</p><p>d</p><p>e</p><p>sa</p><p>b</p><p>re</p><p>),</p><p>li</p><p>p</p><p>ed</p><p>em</p><p>at</p><p>o</p><p>u</p><p>s</p><p>al</p><p>o</p><p>p</p><p>ec</p><p>ia</p><p>,</p><p>S</p><p>P</p><p>T</p><p>L</p><p>T</p><p>re</p><p>at</p><p>m</p><p>en</p><p>t</p><p>O</p><p>ra</p><p>l</p><p>an</p><p>ti</p><p>m</p><p>al</p><p>ar</p><p>ia</p><p>ls</p><p>,</p><p>to</p><p>p</p><p>ic</p><p>al</p><p>/o</p><p>ra</p><p>l/</p><p>in</p><p>tr</p><p>al</p><p>es</p><p>io</p><p>n</p><p>al</p><p>co</p><p>rt</p><p>ic</p><p>o</p><p>st</p><p>er</p><p>o</p><p>id</p><p>s</p><p>O</p><p>ra</p><p>l</p><p>an</p><p>ti</p><p>m</p><p>al</p><p>ar</p><p>ia</p><p>ls</p><p>,</p><p>to</p><p>p</p><p>ic</p><p>al</p><p>/o</p><p>ra</p><p>l/</p><p>in</p><p>tr</p><p>al</p><p>es</p><p>io</p><p>n</p><p>al</p><p>co</p><p>rt</p><p>ic</p><p>o</p><p>st</p><p>er</p><p>o</p><p>id</p><p>s</p><p>T</p><p>re</p><p>at</p><p>m</p><p>en</p><p>t</p><p>fo</p><p>r</p><p>S</p><p>L</p><p>E</p><p>T</p><p>re</p><p>at</p><p>m</p><p>en</p><p>t</p><p>fo</p><p>r</p><p>S</p><p>L</p><p>E</p><p>T</p><p>re</p><p>at</p><p>m</p><p>en</p><p>t</p><p>fo</p><p>r</p><p>S</p><p>L</p><p>E</p><p>H</p><p>y</p><p>d</p><p>ro</p><p>x</p><p>y</p><p>ch</p><p>lo</p><p>ro</p><p>q</p><p>u</p><p>in</p><p>e,</p><p>p</p><p>re</p><p>d</p><p>n</p><p>is</p><p>o</p><p>lo</p><p>n</p><p>e,</p><p>in</p><p>tr</p><p>al</p><p>es</p><p>io</p><p>n</p><p>al</p><p>co</p><p>rt</p><p>ic</p><p>o</p><p>st</p><p>er</p><p>o</p><p>id</p><p>s</p><p>P</p><p>ro</p><p>g</p><p>n</p><p>o</p><p>si</p><p>s</p><p>H</p><p>ai</p><p>r</p><p>lo</p><p>ss</p><p>p</p><p>er</p><p>m</p><p>an</p><p>en</p><p>t</p><p>C</p><p>h</p><p>ro</p><p>n</p><p>ic</p><p>,</p><p>re</p><p>la</p><p>p</p><p>si</p><p>n</p><p>g</p><p>n</p><p>at</p><p>u</p><p>re</p><p>R</p><p>ev</p><p>er</p><p>si</p><p>b</p><p>le</p><p>,</p><p>re</p><p>so</p><p>lv</p><p>ed</p><p>af</p><p>te</p><p>r</p><p>im</p><p>p</p><p>ro</p><p>v</p><p>em</p><p>en</p><p>t</p><p>o</p><p>f</p><p>S</p><p>L</p><p>E</p><p>R</p><p>ev</p><p>er</p><p>si</p><p>b</p><p>le</p><p>,</p><p>re</p><p>so</p><p>lv</p><p>ed</p><p>af</p><p>te</p><p>r</p><p>im</p><p>p</p><p>ro</p><p>v</p><p>em</p><p>en</p><p>t</p><p>o</p><p>f</p><p>S</p><p>L</p><p>E</p><p>P</p><p>er</p><p>si</p><p>st</p><p>s</p><p>ev</p><p>en</p><p>af</p><p>te</p><p>r</p><p>S</p><p>L</p><p>E</p><p>tr</p><p>ea</p><p>tm</p><p>en</p><p>t</p><p>O</p><p>ft</p><p>en</p><p>co</p><p>m</p><p>p</p><p>le</p><p>te</p><p>re</p><p>m</p><p>is</p><p>si</p><p>o</p><p>n</p><p>w</p><p>it</p><p>h</p><p>o</p><p>u</p><p>t</p><p>re</p><p>cu</p><p>rr</p><p>en</p><p>ce</p><p>A</p><p>N</p><p>A</p><p>an</p><p>ti</p><p>n</p><p>u</p><p>cl</p><p>ea</p><p>r</p><p>an</p><p>ti</p><p>b</p><p>o</p><p>d</p><p>ie</p><p>s,</p><p>C</p><p>1</p><p>q</p><p>co</p><p>m</p><p>p</p><p>le</p><p>m</p><p>en</p><p>t</p><p>co</p><p>m</p><p>p</p><p>o</p><p>n</p><p>en</p><p>t</p><p>1</p><p>q</p><p>,</p><p>C</p><p>3</p><p>co</p><p>m</p><p>p</p><p>le</p><p>m</p><p>en</p><p>t</p><p>co</p><p>m</p><p>p</p><p>o</p><p>n</p><p>en</p><p>t</p><p>3</p><p>,</p><p>D</p><p>E</p><p>J</p><p>d</p><p>er</p><p>m</p><p>o</p><p>ep</p><p>id</p><p>er</p><p>m</p><p>al</p><p>ju</p><p>n</p><p>ct</p><p>io</p><p>n</p><p>,</p><p>D</p><p>IF</p><p>d</p><p>ir</p><p>ec</p><p>t</p><p>im</p><p>m</p><p>u</p><p>n</p><p>o</p><p>fl</p><p>u</p><p>o</p><p>re</p><p>sc</p><p>en</p><p>ce</p><p>,</p><p>D</p><p>L</p><p>E</p><p>d</p><p>is</p><p>co</p><p>id</p><p>lu</p><p>p</p><p>u</p><p>s</p><p>er</p><p>y</p><p>th</p><p>em</p><p>at</p><p>o</p><p>su</p><p>s,</p><p>F</p><p>g</p><p>fi</p><p>b</p><p>ri</p><p>n</p><p>o</p><p>g</p><p>en</p><p>,</p><p>Ig</p><p>im</p><p>m</p><p>u</p><p>n</p><p>o</p><p>g</p><p>lo</p><p>b</p><p>u</p><p>li</p><p>n</p><p>,</p><p>S</p><p>L</p><p>E</p><p>sy</p><p>st</p><p>em</p><p>ic</p><p>lu</p><p>p</p><p>u</p><p>s</p><p>er</p><p>y</p><p>th</p><p>em</p><p>at</p><p>o</p><p>su</p><p>s,</p><p>S</p><p>P</p><p>T</p><p>L</p><p>su</p><p>b</p><p>cu</p><p>ta</p><p>n</p><p>eo</p><p>u</p><p>s</p><p>p</p><p>an</p><p>n</p><p>ic</p><p>u</p><p>li</p><p>ti</p><p>s-</p><p>li</p><p>k</p><p>e</p><p>T</p><p>-c</p><p>el</p><p>l</p><p>ly</p><p>m</p><p>p</p><p>h</p><p>o</p><p>m</p><p>a</p><p>Hair and scalp changes in cutaneous and systemic LE</p><p>or around blood vessels [35]. Additional investigations for</p><p>lupus panniculitis include immunophenotyping, molecular</p><p>analysis, and polymerase chain reaction analysis of the</p><p>T-cell receptor-c gene rearrangement [36].</p><p>3.2.2 Differential Diagnosis</p><p>Once lupus panniculitis is suspected, the most important</p><p>condition to rule out is subcutaneous panniculitis-like</p><p>T-cell lymphoma (SPTL) as the condition associates with a</p><p>higher risk of morbidity and mortality. In a study com-</p><p>paring 13 SPTL patients with 7 lupus panniculitis patients,</p><p>SPTL more frequently involved the lower extremities,</p><p>buttocks, and scalp [37]. A common perception in the past</p><p>was that atypical lymphocytes, rimming of fat lobules, and</p><p>abnormal T-cell receptor gene rearrangement were suffi-</p><p>cient differentiating factors; however, recent studies have</p><p>reported overlapping features between the two conditions</p><p>[32]. Recently, Ki-67 hot spots were detected in SPTL</p><p>only, but never in lupus panniculitis, thus providing a</p><p>Fig. 2 Lupus panniculitis/profundus on the scalp. a Localized, well-</p><p>defined erythematous indurated plaque behind the left ear, with</p><p>extension to the left posterior hairline, causing scarring alopecia.</p><p>b Lobular panniculitis with predominantly lymphohistiocytic infiltra-</p><p>tion and hyaline necrosis (hematoxylin and eosin stain; original</p><p>magnification 910)</p><p>Fig. 1 Discoid lupus erythematosus. a Two focal areas of round</p><p>plaques, the right showing adherent scale with follicular plugging,</p><p>and the left showing central atrophy. b Trichoscopic features of</p><p>discoid lupus erythematosus: follicular red dots, thick arborizing</p><p>vessels, scattered dark-brown discoloration, and milky red or white</p><p>areas between the follicles (original magnification 920). c Histolog-</p><p>ical section showing thickened basement membrane, focal basal</p><p>vacuolization along the dermoepidermal junction and follicular</p><p>epithelium; perifollicular lymphocytic infiltration is seen (hema-</p><p>toxylin and eosin stain; original magnification 940). d Direct</p><p>immunofluorescence staining of immunoglobulin M showing thick</p><p>homogenous granular deposition along the basement membrane and</p><p>follicular epithelium</p><p>S. Udompanich et al.</p><p>useful differentiating tool [37]. Other forms of panniculitis</p><p>such as traumatic panniculitis or panniculitis associated</p><p>with morphea and dermatomyositis can affect the scalp.</p><p>3.2.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>In a review of 44 cases of lupus profundus, abnormal</p><p>positive ANA titers were detected in up to 95.2% of</p><p>patients; however, these positive ANA results were of</p><p>varying strength and even the lowest ANA titers were</p><p>considered positive [32]. Other possible abnormal labora-</p><p>tory findings are leukopenia, hypocomplementemia, cir-</p><p>culating rheumatoid factors, and increased ESR. The final</p><p>diagnosis of SLE with fulfilled criteria is only made in</p><p>10–50% of cases [32, 33, 38–40].</p><p>3.2.4 Treatment and Prognosis</p><p>Due to its rarity, studies focusing on treatment and their</p><p>outcome are lacking. In clinical practice, the mainstay</p><p>treatment for lupus panniculitis/profundus is antimalarials.</p><p>Systemic corticosteroids, methotrexate, and dapsone are</p><p>added when the disease cannot be controlled by anti-</p><p>malarials alone, or when there is association with SLE.</p><p>Intralesional corticosteroids could be considered as a</p><p>treatment option in selected cases due to the risk of skin</p><p>atrophy [40]. Most patients respond well to treatment but</p><p>are likely to suffer from relapse after treatment discontin-</p><p>uation [36].</p><p>4 Non-Scarring Alopecia in SLE</p><p>The description of non-scarring alopecia in SLE in the</p><p>SLICC criteria is rather unspecific and refers mainly to</p><p>diffuse hair loss [41]. However, the accumulation of</p><p>research studies has pointed out that non-scarring alopecia</p><p>in SLE can in fact manifest as different clinical patterns,</p><p>with variable risk of systemic disease. Figure 3 offers</p><p>approach considerations for non-scarring alopecia in SLE.</p><p>4.1 Diffuse Non-Scarring Alopecia in SLE</p><p>4.1.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and DIF Features</p><p>Diffuse non-scarring hair loss is the most frequently</p><p>observed type of alopecia in SLE, potentially reflecting a</p><p>patient’s disease activity [4, 42]. While altered immune</p><p>status, ongoing physical stress, and a vigorous medication</p><p>regimen can indirectly result in diffuse hair loss (in the</p><p>form of telogen effluvium or anagen effluvium), recent</p><p>research has suggested that the diffuse hair loss may be a</p><p>direct result of SLE activity on the scalp. Gong et al.</p><p>reported on four SLE patients with severe diffuse non-</p><p>scarring alopecia, involving more than 50% of the scalp</p><p>surface area [2]. All four patients were women with active</p><p>SLE flare-up, and, on physical examination, all had scalp</p><p>erythema, scaling, and a positive gentle hair pull test.</p><p>Trichoscopic examination revealed scalp changes, includ-</p><p>ing scaling, telangiectasia, and focal atrichia. The hair</p><p>shafts were segmentally hypopigmented with uneven</p><p>diameter. These heterogeneous findings have led to spec-</p><p>ulation that damage to the hair matrix and dermal papillae</p><p>in SLE may be a selective process. Histopathological</p><p>findings in all four cases revealed epidermal atrophy with</p><p>focal basal vacuolization, thickening of the basement</p><p>membrane, pigment incontinence, increased catagen/telo-</p><p>gen-to-anagen ratio, and mild perifollicular and perivas-</p><p>cular lymphocytic infiltration. DIF revealed IgG and C3 in</p><p>three cases, and IgM and IgA in one case. All four patients</p><p>received treatment according to their disease severity, and</p><p>all achieved complete hair regrowth without recurrence [2].</p><p>From our experience, the extent of hair loss varies</p><p>tremendously from patient to patient, and even in the same</p><p>patient at different points in time. During the follow-up</p><p>period when the disease is quiescent, most patients still</p><p>complain of some degree of hair loss, and physical</p><p>examination indeed revealed diffuse thinning (Fig. 4a),</p><p>with sparse to abundant interfollicular telangiectasia on</p><p>trichoscopy (Fig. 4b). It is possible that some background</p><p>SLE activity is always present on the scalp, and gradual</p><p>accumulation of inflammation along certain hair follicles is</p><p>enough to shorten the anagen phase or induce anagen</p><p>arrest. However, the correlation with SLE exacerbation</p><p>seems to exist only when the alopecia is severe, often</p><p>involving more than 50% of the scalp surface area. This</p><p>may represent a vigorous and synchronized attack on the</p><p>hair follicles. Histopathological findings demonstrate</p><p>specific LE changes (Fig. 4c). In addition, there is usually</p><p>an increased percentage of the catagen/telogen-to-anagen</p><p>ratio, suggesting that SLE has a predilection for anagen</p><p>hair, in a similar manner to AA, which is also an autoim-</p><p>mune condition. DIF further supports the diagnosis of</p><p>cutaneous LE, with homogenous or focal granular deposi-</p><p>tion of mainly IgG and C3 along the DEJ and follicular</p><p>epithelium (Fig. 4d).</p><p>Other important forms of non-scarring alopecia in SLE</p><p>are telogen effluvium and anagen effluvium. Both condi-</p><p>tions appear simultaneously with SLE exacerbation, and its</p><p>vigorous management occurs simultaneously. As these</p><p>conditions relate to SLE, but do not exhibit specific LE</p><p>changes on histopathology, we propose they are classified</p><p>as LE non-specific alopecia. Telogen effluvium is an</p><p>increase in normal telogen hair shedding, occurring</p><p>Hair and scalp changes in cutaneous and systemic LE</p><p>approximately 3–6 months after a precipitating event.</p><p>In</p><p>SLE, it is likely that telogen effluvium results from severe</p><p>catabolic effects and elevated levels of circulating proin-</p><p>flammatory cytokines around the hair follicles [42]. Drugs</p><p>used in SLE have been reported to cause telogen effluvium,</p><p>including chloroquine, hydroxychloroquine, acitretin, aza-</p><p>thioprine, cyclosporine and dexamethasone [43]. On</p><p>examination, diffuse non-scarring alopecia is mild but may</p><p>be accompanied by some short regrowing hairs. The</p><p>severity of hair loss can be a convenient discriminating</p><p>factor as when there is more than 50% hair loss, telogen</p><p>effluvium is unlikely. On trichoscopy, empty hair follicles</p><p>and numerous short regrowing hairs are the most common</p><p>findings [44], while histopathology reveals normal total</p><p>hair count, normal number of terminal hairs, and increased</p><p>telogen count to more than 20% in the absence of any</p><p>inflammation or scarring [20].</p><p>Anagen effluvium is caused by the direct insult of</p><p>chemotherapy on the rapidly dividing hair follicle cells in</p><p>the anagen phase, leading to sudden arrest of mitotic</p><p>activity [45]. Hair shedding begins 1–3 weeks after initi-</p><p>ation of chemotherapy, and, since 90% of scalp hair is in</p><p>the anagen phase, patients can experience extensive hair</p><p>loss [46]. However, the process is reversible and hair tends</p><p>to grow back in 3–6 months after chemotherapy cessation.</p><p>Cyclophosphamide, an alkylating agent frequently used</p><p>during SLE flare-ups, can cause anagen effluvium in more</p><p>than 60% of patients [46]. Another possible mechanism in</p><p>SLE patients is that severe disease exacerbations can</p><p>trigger a temporary shutdown of the follicular stem cells</p><p>and hair matrix cells [42].</p><p>4.1.2 Differential Diagnosis</p><p>Other forms of non-scarring alopecia must be considered,</p><p>namely androgenic alopecia and diffuse AA. History and</p><p>physical examination are usually sufficient; for example,</p><p>the chronic onset and specific pattern of hair loss in</p><p>androgenic alopecia are familiar to dermatologists. Diffuse</p><p>AA is sometimes difficult to diagnose clinically or tricho-</p><p>scopically. Scalp biopsy for horizontal and vertical sections</p><p>can help to establish the diagnosis.</p><p>4.1.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>This type of non-scarring alopecia was initially observed</p><p>and recognized in patients with SLE and therefore is</p><p>exclusive to the disease. In severe cases with more than</p><p>50% hair loss, the correlation with disease activity is</p><p>almost definite [2]. However, as the condition may be</p><p>underrecognized, studies on its true relation with SLE</p><p>disease activity are lacking. Patients from previous studies</p><p>have complained of malar rash, oral ulcers, photosensitiv-</p><p>ity, and other extracutaneous symptoms of SLE [2]. In</p><p>addition to these manifestations, our patients with severe</p><p>diffuse hair loss were admitted with class V lupus nephritis</p><p>and neuropsychiatric symptoms.</p><p>Fig. 3 Approach considerations</p><p>for non-scarring alopecia in</p><p>SLE. SLE systemic lupus</p><p>erythematosus, AA alopecia</p><p>areata</p><p>S. Udompanich et al.</p><p>4.1.4 Treatment and Prognosis</p><p>Treatment of SLE itself is usually sufficient and no pro-</p><p>gression of hair loss is noted after 2–3 weeks of treatment.</p><p>Prominent hair regrowth was observed after 7–8 weeks and</p><p>all patients eventually achieved complete hair regrowth</p><p>without any recurrence [2].</p><p>4.2 Patchy, Non-Scarring Alopecia in SLE</p><p>4.2.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and DIF Features</p><p>During the initial presentation of SLE or at the time of</p><p>disease exacerbations, localized, well-defined patches of</p><p>partial or total hair loss may appear on the scalp. Closer</p><p>inspection of the lesion reveals no evidence of scarring,</p><p>only mild erythema and yellow scale [47]. The hair shafts</p><p>themselves are thin and hypopigmented, suggesting a direct</p><p>insult to the hair follicles (Fig. 5a). This form of alopecia is</p><p>fairly common, contributing up to 15% of alopecia in SLE,</p><p>but has so far received little attention in the literature [4].</p><p>Trichoscopic examination of the hair loss region not only</p><p>confirms hair shaft thinning and hypopigmentation but also</p><p>exhibits unique scalp changes such as polymorphous</p><p>telangiectasia located in the interfollicular area (Fig. 5b)</p><p>[48]. It was speculated that the visible angiotelectasis is</p><p>caused by local vasculitis, and that the pathology may</p><p>result in local inflammation of hair follicles and consequent</p><p>hair loss. Similar to the diffuse form, histological exami-</p><p>nation of patchy alopecia in SLE shows epidermal atrophy,</p><p>focal basal vacuolar degeneration in the epidermis and</p><p>follicular infundibula (Fig. 5c), perieccrine and perivascu-</p><p>lar lymphoplasmacytic inflammation, and increased dermal</p><p>mucin. Deep perifollicular inflammation and an increased</p><p>catagen/telogen percentage in the affected areas was also</p><p>documented. In our opinion, the pathophysiology of pat-</p><p>chy, non-scarring alopecia in SLE may be similar to those</p><p>of severe diffuse type, and that a synchronized and intense</p><p>attack on the hair follicles is involved, but in this case the</p><p>Fig. 4 Diffuse non-scarring alopecia in systemic lupus erythemato-</p><p>sus. a Mild diffuse non-scarring alopecia and severe diffuse non-</p><p>scarring alopecia. b Trichoscopic examination showing hair shaft</p><p>thinning and numerous interfollicular arborizing telangiectasia (orig-</p><p>inal magnification 920). c Epidermal atrophy, basal vacuolization</p><p>along the basement membrane and follicular epithelium with</p><p>melanophages and superficial perivascular lymphohistiocytic infiltra-</p><p>tion (hematoxylin and eosin stain; original magnification 940).</p><p>d Direct immunofluorescence showing homogenous granular depo-</p><p>sition of immunoglobulin M along the basement membrane, and</p><p>homogenous granular deposition of complement 3 along the follicular</p><p>epithelium</p><p>Hair and scalp changes in cutaneous and systemic LE</p><p>inflammation is concentrated in one region. To date, no</p><p>data have been reported on the DIF findings of this con-</p><p>dition. From our experience, DIF from the non-scarring</p><p>alopecic patch resembles those of acute cutaneous LE.</p><p>Epidermal nuclear staining and homogenous granular</p><p>deposition of IgG, IgM, and C3 along the DEJ and follic-</p><p>ular epithelium were observed (Fig. 5d).</p><p>4.2.2 Differential Diagnosis</p><p>In clinical practice, when localized non-scarring alopecia is</p><p>encountered, the main differential diagnosis is AA. Werth</p><p>et al. examined a cohort of 39 patients with DLE and mild</p><p>SLE, and found the incidence of AA to be higher than</p><p>general dermatologic patients (10 and 0.42%, respectively)</p><p>[49]. Biopsies taken from the alopecic patches were con-</p><p>cluded to be consistent with AA, with an increased number</p><p>of catagen hairs and lymphocytic infiltration along fibrous</p><p>tracts and hair follicles. However, DIF studies showed</p><p>homogenous granular deposition of IgG or IgM along the</p><p>DEJ, which was absent on normal scalp specimens taken</p><p>from the same patient. This finding strongly suggests LE</p><p>activity on the alopecic patch. Subsequent publications</p><p>believe that the coexistence between SLE and AA was</p><p>merely an incidental finding and that clinicians may have</p><p>misdiagnosed patchy alopecia in SLE as AA [50]. The</p><p>pathophysiological process of patchy, non-scarring alope-</p><p>cia in SLE is still controversial, whether the condition is</p><p>one of the hair loss presentations from SLE or coexistent</p><p>AA. Due to this inconclusive relationship, we propose that</p><p>AA falls into the group of non-specific LE. Moreover, the</p><p>pathological discriminating features for both conditions are</p><p>unclear. Sperling et al. believed that the peribulbar</p><p>mononuclear cell infiltrate found adjacent to the anagen</p><p>hair bulb is denser in SLE, when compared with AA [47].</p><p>The percentage of catagen and telogen hairs is greatly</p><p>increased [51]. On the contrary, a recent comparative study</p><p>of 21 patients with non-patchy alopecia in SLE and 21 AA</p><p>patients concluded that while AA lesions were character-</p><p>ized by the usual swarm of bee-like lymphocytic inflam-</p><p>mations around the hair</p><p>follicles, this feature is absent in</p><p>SLE patients. The study reported specific trichoscopic</p><p>features, including exclamation mark hairs, black dots, and</p><p>broken hairs, which were only found in AA lesions. The</p><p>study also reported peripilar signs and perifollicular red</p><p>dots as specific trichoscopic features of patchy, non-scar-</p><p>ring alopecia in SLE, thus providing useful clues for the</p><p>differential diagnosis [48]. In general, further studies are</p><p>required to draw definite conclusions on their histological</p><p>differences, but clinicians should always rule out the pos-</p><p>sibility of AA whenever diagnosing patchy alopecia in</p><p>SLE.</p><p>Both clinical and histological features of patchy alope-</p><p>cia in SLE may also resemble hair loss found in secondary</p><p>syphilis. Syphilitic alopecia can be diffuse or localized, but</p><p>the most common pattern has been described as moth-</p><p>eaten, with multiple small areas of non-scarring alopecia</p><p>with an irregular, poorly defined border [52]. Trichoscopy</p><p>Fig. 5 Patchy, non-scarring</p><p>alopecia in systemic lupus</p><p>erythematosus. a Solitary, well-</p><p>defined non-scarring alopecia</p><p>on the left vertex.</p><p>b Trichoscopic features</p><p>showing hair shaft thinning and</p><p>hypopigmentation, along with</p><p>multiple interfollicular</p><p>telangiectasia on the scalp</p><p>(original magnification 920).</p><p>c Lymphocytic infiltration and</p><p>basal vacuolization of the</p><p>follicular epithelium</p><p>(hematoxylin and eosin stain;</p><p>original magnification 960).</p><p>d Direct immunofluorescence</p><p>staining of immunoglobulin M</p><p>showing thick homogenous</p><p>granular deposition along the</p><p>basement membrane and</p><p>follicular epithelium</p><p>S. Udompanich et al.</p><p>shows yellow dots, black dots, a reduced number of ter-</p><p>minal hairs, and intense red-brown pigmentation [52, 53].</p><p>On histology, lymphohistiocytic inflammatory infiltrate</p><p>with abundant plasma cells surrounds the fibrous streamer</p><p>and the bulb [54]. Distinguishing features between syphi-</p><p>litic alopecia and AA have long been a subject of debate as</p><p>some believe the presence of plasma cells and the absence</p><p>of eosinophils are highly suggestive of syphilitic alopecia</p><p>[54]. Some histological features may help to distinguish</p><p>SLE from its histological mimics, such as increased dermal</p><p>mucin, perieccrine lymphocytic infiltration, and focal basal</p><p>vacuolization of the hair follicles [51]. Now that patchy</p><p>alopecia in SLE has been increasingly recognized, it should</p><p>also be added into the frame.</p><p>Finally, an early form of DLE may present as localized,</p><p>non-scarring alopecic patches on the scalp in which,</p><p>without any treatment, epithelial changes and scarring</p><p>alopecia will inevitably pursue. Whether non-scarring,</p><p>patchy alopecia in SLE is the same entity as early DLE is</p><p>questionable, especially when DLE is regarded as biphasic,</p><p>causing non-scarring alopecia in the beginning and irre-</p><p>versible scarring alopecia later on. However, the fact that</p><p>patchy, non-scarring alopecia in SLE occurs abruptly and</p><p>most predominantly in severe uncontrolled SLE cases has</p><p>marked resemblance with AA, and acute LE changes on</p><p>pathology/DIF indicates that the condition may be more</p><p>comparable to acute cutaneous LE, rather than DLE.</p><p>4.2.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>The condition is exclusive to SLE. There is currently no</p><p>documentation on non-scarring alopecic patches, with LE</p><p>features on histopathology, occurring outside the context of</p><p>SLE. The correlation with disease activity is not confirmed,</p><p>but most literature regards the condition as a marker for</p><p>severe, uncontrolled disease [47].</p><p>4.2.4 Treatment and Prognosis</p><p>Similar to the diffuse form, patchy, non-scarring alopecia is</p><p>reversible after treatment of SLE. An increase in vellus hair</p><p>is the earliest sign that emerges, while hair shaft</p><p>hypopigmentation is the earliest feature to disappear, fol-</p><p>lowed by the disappearance of telangiectasia [48].</p><p>4.3 Lupus Hair</p><p>4.3.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and DIF Features</p><p>Originally proposed by Armas-Cruz et al. in 1958, lupus hair</p><p>is used to describe a distinct pattern of non-scarring alopecia</p><p>in chronically active SLE patients [55]. Lupus hair can be</p><p>detected most frequently along the anterior hairline, the hair</p><p>appears short, fragile, coarse and dry, and sometimes mild</p><p>erythema is present in the background (Fig. 6a). Hair growth</p><p>is speculated to be retarded, producing a disheveled</p><p>appearance. Other peripheral scalp regions can also be</p><p>affected but may be less obvious. Hair abnormalities</p><p>described in lupus hair do not always demonstrate hair loss;</p><p>however, in most cases, this change of hair structure asso-</p><p>ciateswith non-scarring alopecia. The incidence ranges from</p><p>10.7 to 30% of all SLE patients. Although lupus hair mani-</p><p>fests in a number of patients with active SLE, this condition</p><p>is still not definitively defined. Trichoscopic, histopatho-</p><p>logic, and DIF features of lupus hair are still unknown. Only</p><p>microscopic examination of lupus hair from the front hairline</p><p>has been reported, revealing a pointed end, which suggested</p><p>hair growth retardation [56]. In our SLE clinics, we have</p><p>come across numerous patients with short, brittle hair along</p><p>their frontal hairline. Hair shaft thinning, hair shaft</p><p>hypopigmentation, broken hairs, and interfollicular telang-</p><p>iectasia were apparent on trichoscopic examination</p><p>(Fig. 6b). These findings are consistent with other forms of</p><p>non-scarring alopecia in SLE. A biopsy taken from our</p><p>patient revealed focal basal vacuolization along theDEJ, and</p><p>sparse superficial perivascular lymphocytic infiltration</p><p>(Fig. 6c). On DIF, granular deposition of IgG along the</p><p>follicular epithelium was observed (Fig. 6d).</p><p>4.3.2 Differential Diagnosis</p><p>The coarse, dry, and dull appearance of lupus hair can</p><p>resemble hair abnormalities found in patients with</p><p>hypothyroidism [55]. The receding hairline may need to be</p><p>differentiated with androgenetic alopecia, as well as frontal</p><p>fibrosing alopecia. Both conditions do not present brittle</p><p>hairs, which can be examined by performing a tug test.</p><p>Scalp biopsy for horizontal and vertical sections should be</p><p>performed, especially in controversial cases. A recent</p><p>report of two cases of histopathologically proven frontal</p><p>fibrosing alopecia-like cutaneous LE stressed the impor-</p><p>tance of skin biopsy [57]. Other differential diagnoses</p><p>belong in the group of acquired hair shaft disorders asso-</p><p>ciated with increased hair fragility, such as trichorrhexis</p><p>nodosa or bubble hair, a condition that is caused by hair</p><p>weathering.</p><p>4.3.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>Lupus hair is a distinct finding of SLE that correlates with</p><p>severe and chronic disease [42]. A previous study found</p><p>that in all patients, the development of lupus hair coincided</p><p>with clinical and laboratory evidence of disease activity;</p><p>Hair and scalp changes in cutaneous and systemic LE</p><p>however, the details of this clinical and laboratory evi-</p><p>dence, as well as the statistical evaluation for this corre-</p><p>lation, were omitted [56].</p><p>4.3.4 Treatment and Prognosis</p><p>After adequate treatment of SLE flare-up, patients’ hair and</p><p>scalp may return to normal. Nonetheless, lupus hair tends</p><p>to persist for longer and can be present even when alopecia</p><p>has resolved [56].</p><p>4.4 Linear and Annular Lupus Panniculitis</p><p>of the Scalp</p><p>4.4.1 Clinical Presentation, Trichoscopic,</p><p>Histopathological, and DIF Features</p><p>LALPS was first reported by Nagai et al. in 2003 [58]. The</p><p>condition represents a unique type of alopecia which,</p><p>despite affecting the subcutaneous tissue, is non-scarring</p><p>and always reversible. This rare entity exists in only 10</p><p>cases reported from different parts of the world, predomi-</p><p>nantly from East Asia, hence its true incidence is unknown.</p><p>Patients present with long-standing peculiar linear, annular,</p><p>or arc-shaped patches of non-scarring alopecia along the</p><p>suspected Blaschko’s line of the scalp. At times, the patch</p><p>may evolve into erythematous plaque with mild tenderness,</p><p>but signs of DLE such as skin atrophy and sclerotic</p><p>changes are usually absent (Fig. 7a). Reported trichoscopic</p><p>features include yellow dots, perifollicular white scales,</p><p>and some patchy erythematous areas [59]. In addition to</p><p>these features, we observed numerous thick arborizing</p><p>vessels, large yellow dots, and black dots in our patients.</p><p>On histology, the abnormality is confined to the sub-</p><p>cutaneous tissue. The epidermis is often unremarkable,</p><p>although basal vacuolar degeneration and epidermal atro-</p><p>phy can still be present. The dermis shows dense perifol-</p><p>licular, perivascular, and perieccrine lymphocytic</p><p>infiltration, while the subcutaneous tissue resembles that of</p><p>lupus panniculitis, showing lobular lymphocytic infiltration</p><p>(Fig. 7b), hyaline fat degeneration, fat necrosis, and</p><p>abundant mucin deposition. DIF from previous cases</p><p>showed granular deposition of IgG or IgM along the</p><p>basement membrane and at the peribulbar area. In some</p><p>cases, DIF was negative for all IGs and C3 [60].</p><p>A plausible explanation for its non-scarring nature could</p><p>be that the pathology is concentrated deep down the hair</p><p>follicles, well below the stem cells reservoir. Alternatively,</p><p>it is possible that we regard the condition as non-scarring</p><p>because it has always been detected and treated early, as</p><p>alopecia is an alerting early sign that typically results in</p><p>patients seeking prompt consultation. A report of sclero-</p><p>dermic linear lupus panniculitis in two cases, both with</p><p>long-standing clinical course, supports the relationship</p><p>between disease duration and the scarring process [34]. It is</p><p>unclear why these lesions follow the lines of Blaschko, in</p><p>which the exact pattern on the head and neck is unknown.</p><p>Nevertheless, it has been hypothesized that linear</p><p>Fig. 6 Lupus hair. a Frontal</p><p>hairline recession with short,</p><p>coarse, dry, and lustreless hair.</p><p>b Trichoscopic examination of</p><p>the frontal hairline showing hair</p><p>shaft thinning and</p><p>hypopigmentation; mild scalp</p><p>erythema is seen in the</p><p>background (original</p><p>magnification 920).</p><p>c Thickened basement</p><p>membrane with a few scattered</p><p>necrotic keratinocytes in the</p><p>epithelium; mild focal basal</p><p>vacuolization along the</p><p>dermoepidermal junction with</p><p>melanophages below; and mild</p><p>superficial perivascular</p><p>lymphocytic infiltration</p><p>(hematoxylin and eosin stain;</p><p>original magnification 940).</p><p>d Direct immunofluorescence</p><p>staining of immunoglobulin G</p><p>showing homogenous granular</p><p>deposition along the follicular</p><p>epithelium</p><p>S. Udompanich et al.</p><p>cutaneous eruptions occur as a result of a genetically pro-</p><p>grammed cloning of cells along Blaschko’s lines during</p><p>early embryogenesis [34].</p><p>4.4.2 Differential Diagnosis</p><p>LALPS should be differentiated from morphea en coup de</p><p>sabre, although the latter typically presents with scarring</p><p>sclerotic plaques. AA and trichotillomania may produce</p><p>non-scarring alopecia with bizarre configurations. In</p><p>addition, whenever there is lymphocytic involvement of</p><p>subcutaneous tissue, SPTL must be ruled out. As men-</p><p>tioned above, the classic form of lupus panniculitis on the</p><p>scalp is usually scarring, and does not follow the lines of</p><p>Blaschko. In comparison to the classic form, LALPS</p><p>occurs in a younger age group, and has a higher frequency</p><p>of male patients and lower rate of association with SLE</p><p>[60].</p><p>4.4.3 Relationship with SLE/Correlation with Disease</p><p>Activity</p><p>LALPS most likely occurs as an isolated cutaneous lesion,</p><p>and development of SLE is probably the rarest among all</p><p>types of alopecia. Approximately 50% of patients had a</p><p>positive ANA test, but a final diagnosis of SLE has not</p><p>been reported.</p><p>4.4.4 Treatment and Prognosis</p><p>Oral hydroxychloroquine and oral and intralestional corti-</p><p>costeroids were the treatment of choice. A majority of</p><p>patients achieved complete recovery within 1 year. Few</p><p>patients had recurrence on the same or different parts of the</p><p>scalp.</p><p>5 Miscellaneous Findings</p><p>Secondary cutaneous lesions related to SLE can involve the</p><p>scalp. For example, accumulation of mucin around hair</p><p>follicles and sebaceous glands can lead to papulonodular</p><p>mucinosis. Up to 79% of the disease associates with SLE</p><p>[61]. When these lesions appear on the scalp, diffuse non-</p><p>scarring alopecia can follow and, if left untreated, can</p><p>result in scarring and irreversible hair loss [62]. This con-</p><p>dition is termed alopecia mucinosa, or follicular mucinosis.</p><p>Basaloid follicular hamartoma is a form of follicular</p><p>alteration that has been reported to associate with SLE and</p><p>can also present on the scalp [63–65]. Clinically, patients</p><p>present with multiple follicular papular lesions, along with</p><p>diffuse non-scarring alopecia. Aggregation of basaloid</p><p>cells can be seen on histology, similar to those found in</p><p>trichoepitheliomas [63, 65]. In a case report by Smith and</p><p>Skelton, oral and topical retinoids proved to be beneficial</p><p>[63].</p><p>Other miscellaneous findings include diffuse dystrophic</p><p>calcinosis cutis on the scalp following the development of</p><p>DLE, and scarring alopecia in a patient with long-standing</p><p>SLE [66]. This is a rather rare phenomenon as dystrophic</p><p>calcinosis cutis normally occurs in systemic sclerosis and</p><p>juvenile dermatomyositis. Morphea and cutaneous LE</p><p>developing in the same lesion has been reported in previous</p><p>literature [34, 67–74]. Possible mechanisms are that both</p><p>diseases coexisted or that one evolved into the other;</p><p>however, there are no reports of such combinations on the</p><p>scalp.</p><p>Finally, it is important to bear in mind that SLE can alter</p><p>hair quality without any hair loss. Seyahi et al. quantita-</p><p>tively compared the hair thickness of SLE patients with</p><p>that of patients with rheumatoid arthritis, as well as healthy</p><p>controls [75]. The mean hair diameter in SLE patients was</p><p>significantly lower than that of healthy controls, even after</p><p>age-adjusted analysis. Among the SLE group, no differ-</p><p>ences in hair diameter were seen in patients using aza-</p><p>thioprine/cyclophosphamide and corticosteroids when</p><p>compared with patients who were not using those agents.</p><p>This finding eliminates the effect of a drug as a confounder.</p><p>However, no difference was seen between SLE and</p><p>rheumatoid arthritis, suggesting that the apparent reduction</p><p>in hair diameter could have reflected the state of being ill.</p><p>Hair shaft hypopigmentation is not uncommon in our SLE</p><p>clinics. A valid explanation could be the effect of chloro-</p><p>quine. However, a majority of our patients are taking</p><p>hydroxychloroquine, for which reports of hair hypopig-</p><p>mentation are exceedingly rare. Hair lightening after</p><p>Fig. 7 Linear and annular lupus panniculitis of the scalp. a Linear</p><p>non-scarring alopecic patch in a bizarre configuration. b Lobular</p><p>panniculitis with lymphocytes and deep lymphocytic infiltration</p><p>surrounding a hair follicle (hematoxylin and eosin stain; original</p><p>magnification 910)</p><p>Hair and scalp changes in cutaneous and systemic LE</p><p>chloroquine use was even reported to revert back to normal</p><p>after switching to hydroxychloroquine. Whether or not</p><p>SLE itself can alter hair pigmentation is unknown [76].</p><p>6 Conclusions</p><p>Hair and scalp involvement in SLE is common, with a wide</p><p>variety of clinical manifestations. Scarring alopecia such as</p><p>DLE and lupus panniculitis/profundus are familiar condi-</p><p>tions and are typically confined to the skin. Non-scarring</p><p>alopecia in SLE comprises different clinical phenotypes,</p><p>including the diffuse type, patchy type, and the renowned</p><p>lupus hair. These conditions are believed to reflect SLE</p><p>disease activity. LALPS is non-scarring despite involving</p><p>subcutaneous tissue. Emerging studies suggest that these</p><p>non-scarring conditions may have specific LE changes on</p><p>histopathology and are often reversible after SLE treat-</p><p>ment. Other miscellaneous conditions related to SLE can</p><p>affect the scalp. In addition, reduced hair diameter and hair</p><p>shaft hypopigmentation can occur without any evidence of</p><p>hair loss. Physicians should always spare some time to</p><p>examine the hair and scalp</p><p>as they can provide valuable</p><p>clues for the diagnosis and monitoring of SLE.</p><p>Compliance with Ethical Standards</p><p>Funding No funding was received to assist in the preparation of this</p><p>review.</p><p>Conflicts of interest Siriorn Udompanich, Kumutnart Chanprapaph,</p><p>and Poonkiat Suchonwanit have no conflicts of interest to declare.</p><p>References</p><p>1. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla</p><p>P, et al. Systemic lupus erythematosus: clinical and immunologic</p><p>patterns of disease expression in a cohort of 1000 patients. The</p><p>European Working Party on Systemic Lupus Erythematosus.</p><p>Medicine (Baltimore). 1993;72(2):113–24.</p><p>2. 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Udompanich et al.</p><p>Hair and Scalp Changes in Cutaneous and Systemic Lupus Erythematosus</p><p>Abstract</p><p>Introduction</p><p>Diagnostic Criteria, Classifications, Scoring Systems, and the Incorporation of Alopecia</p><p>Scarring Alopecia in Systemic Lupus Erythematosus (SLE)</p><p>Discoid Lupus Erythematosus</p><p>Clinical Presentation, Trichoscopic, Histopathological, and Direct Immunofluorescence (DIF) Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Lupus Panniculitis/Lupus Profundus</p><p>Clinical Presentation, Trichoscopic, Histopathological, and DIF Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Non-Scarring Alopecia in SLE</p><p>Diffuse Non-Scarring Alopecia in SLE</p><p>Clinical Presentation, Trichoscopic, Histopathological, and DIF Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Patchy, Non-Scarring Alopecia in SLE</p><p>Clinical Presentation, Trichoscopic, Histopathological, and DIF Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Lupus Hair</p><p>Clinical Presentation, Trichoscopic, Histopathological, and DIF Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Linear and Annular Lupus Panniculitis of the Scalp</p><p>Clinical Presentation, Trichoscopic, Histopathological, and DIF Features</p><p>Differential Diagnosis</p><p>Relationship with SLE/Correlation with Disease Activity</p><p>Treatment and Prognosis</p><p>Miscellaneous Findings</p><p>Conclusions</p><p>References</p>