Alopecia

Three types of alopecia can be detected in patients with LE (Sontheimer and Provost 1996). In addition to the permanent scarring alopecia associated with discoid lupus lesions, patients with SLE may experience transient alopecia with increased disease activity. Two types of transient hair loss, a result of the severe catabolic effect of the Table 7.4. Comparative histologic findings in chilblain lupus erythematosus (LE) vs idiopathic chilblains (see Cribier et al. 2001,Viguier et al. 2001)...

Lupus Erythematosus and Sjgrens Syndrome

Sjogren's syndrome (SS) can be associated with all connective tissue diseases. The overlap syndromes of SS and other dermatoses, LE included, form a distinct subtype in the classification of SS. The incidence of SS in connective tissue diseases is different. Mostly, this association appears in systemic sclerosis. Immunologic markers of SS, anti-Ro SSA and anti-La SSB antibodies, occur in all connective tissue diseases, sometimes without clinical evidence. Provost et al. (Provost et al. 1988)...

Graftvs Host Disease as a Model of Systemic Lupus Erythematosus

It is well known that chronic graft-vs-host (GVH) disease in mice has similarities to human SLE, and several models have been used for these investigations. The GVH model offers significant advantages over the existing, spontaneous SLE-prone mice in that it can be reliably induced and it follows a predictable, relatively short time course. Gleichmann and associates successfully induced a syndrome strongly resembling SLE in a suitable chronic GVH disease made in nonirradiated, H-2-incompati-ble...

In Cutaneous Lupus Erythematosus

Lupus erythematosus (LE) is an autoimmune disorder associated with specific and nonspecific skin lesions, UV sensitivity, anti-DNA antibodies, and increased interferon (IFN)-a p production. Although the histopathology of LE is well defined, the pathogenesis of skin lesions in LE is still insufficiently understood and does not explain all the clinical aspects of LE. Approximately 55 of patients with systemic LE (SLE) develop clinically distinctive skin lesions, whereas patients with specific LE...

Chronic Cutaneous Lupus Erythematosus Discoid Lupus Erythematosus

Discoid LE (DLE) is the most common form of LE. Clinically, the head and neck region is affected in most cases. On the face, there may be a butterfly distribution. However, in some cases, the trunk and upper extremities can be also involved. Lesions consist of erythematous scaly patches and plaques. Histologically, in DLE the epidermis and dermis are affected, and the subcutaneous tissue is usually spared. However, patchy infiltrates may be present. Characteristic microscopic features are...

DIF Findings in Systemic Lupus Erythematosus Table 221

The DIF findings in biopsy samples obtained from typical SLE lesions are similar to those seen in DLE or SCLE IgG, IgM, IgA, and C3 are most frequently detected, but other complement components and fibrin may be also present. The intensity of the LBT result in lesional skin was shown to correlate with serum titers of anti-DNA antibodies and with disease activity (Sontheimer and Gilliam 1979). As in other forms of Fig. 22.3. Perivascular deposits of IgG around a dermal vessel in lesional skin...

Lupus Erythematosus Tumidus

LE tumidus (LET) is a probably not so infrequent variety of CLE that is defined histopathologically by LE-type dermal inflammation, accumulation of mucin, and the absence of epidermal involvement (Kuhn et al. 2003). Clinically, it corresponds to erythematous discoid lesions most often of the face (zygomatic area) that are persistent and without a tendency for atrophy and scarring (Kuhn et al. 2000). Lymphocytic infiltration Jessner-Kanof is defined practically in the same way (Jessner and...

Characteristics of Drug Induced Lupus Erythematosus

Systemic lupus erythematosus, often abbreviated SLE, is a serious autoimmune syndrome that usually affects young women. Most lupus is idiopathic, which means that its cause is unknown, but approximately 10 is associated with the use of specific drugs (Adams and Hess 1991). The diagnosis of drug-induced lupus is made on the same basis as idiopathic lupus in addition, the symptoms must have begun after initiation of treatment with a drug and must resolve on discontinuation of that drug treatment....

Clinical Photosensitivity in Lupus Erythematosus

Despite the numerous anecdotal reports and the overwhelming clinical evidence demonstrating the clear relationship between sunlight exposure and the manifestations of LE, almost no systematic studies on photobiologic reactivity in patients with this disease existed until the early 1960s (Hasan et al. 1997, Millard et al. 2000, Leenu-taphong and Boonchai 1999, Walchner et al. 1997). The first group to phototest a larger number (n 25) of patients with LE was Epstein et al. (Epstein et al. 1965)....

And Systemic Lupus Erythematosus

Christof Specker, Matthias Schneider Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune disease characterized by highly varied clinical manifestations in association with autoantibody production (antinuclear antibodies ANAs , anti-double-stranded DNA ds-DNA antibodies, and anti-extractable nuclear antigen antibodies). Next to, for instance, kidneys, brain, heart, and joints, the skin is one of the organs typically affected in lupus. Cutaneous manifestations of lupus...

Experimental Models of Lupus Erythematosus

The etiology and pathogenesis of autoimmune diseases cannot be readily analyzed without appropriate animal models, although no single animal model perfectly mimics a human disease. Animal models are commonly used to study the genetic, environmental, and pathogenic aspects of autoimmune diseases. Regarding experimental autoimmune diseases, these models can be divided into several broad groups (a) inbred mice that spontaneously develop a disease similar to human systemic lupus erythematosus (SLE)...

Apoptosis Genes and Photosensitivity in Lupus

Apoptosis is a form of programmed cell death, over 6-48 h, that is characterized by cell shrinkage and nuclear condensation in response to the activation of the enzyme caspase 3 (Elkon 1997, Salmon and Gordon 1999). On early apoptotic keratinocytes, Casciola-Rosen (1997) reported the formation of surface blebs, which are highly enriched with several lupus autoantigens, including Ro SSA in genetically susceptible individuals, expression of this autoantigen is proposed to initiate an autoantibody...

Lupus Erythematosus and Neutrophilic Dermatosis Sweets Syndrome

Neutrophilic dermatosis was first reported in association with SCLE by Goette in 1985. The next patient, described by Levenstein et al. (Levenstein et al. 1991), had a simultaneous appearance of both SCLE and Sweet's syndrome. The patient was later investigated for SS, and the latter was diagnosed in him. Therefore, the authors recommended that each patient with the clinical picture of both diseases be investigated for SS. Their suggestion is based on the article by Katayama et al. (Katayama et...

Subacute Cutaneous Lupus Erythematosus

The term subacute cutaneous lupus erythematosus was coined in 1977 by Gilliam (Gilliam 1977) and further characterized by Sontheimer et al. (Sontheimer et al. 1979) in 1979. The authors introduced a previously undescribed variant of LE with skin lesions at the neck, shoulders, upper thorax, and arms. Clinically, recurrent annular polycyclic or papulosquamous lesions involve the upper trunk, extensor regions of the arms, and face and neck region. The histopathologic features of SCLE are almost...

Maculopapular Exanthemas

Generalized exanthemas of SLE may appear as transitory indistinct morbilliform macular rashes that regress after hours or days and may wax and wane parallel to disease activity they may persist, however, and transform into more stable macular lesions that are well demarcated, are slightly hypertrophic and scaly, and somewhat resemble the lesions of SCLE. Some may acquire annular shapes or a tylotic morphology (e. g., chilblain lupus). All exanthemas of SLE, except the morbilliform rashes, are...

Apoptosis in Lupus Erythematosus17

FeLipe Andrade, Antony Rosen, Livia CascioLa-RoseN Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by chronic, inflammatory damage of numerous tissues. The highly specific clinical phenotypes of SLE, the unique pathology, and the very specific autoantibody response associated with these phenotypes have provided critical insights into the pathogenesis of lupus. In this regard, photosensitive lupus skin disease and neonatal lupus have been...

Discoid Lupus Erythematosus of the Oral Mucosa

DLE of the oral mucosa is not an infrequent finding. It begins as one or a few round, well-demarcated erythematous plaques with patchy and streaky white hyperkeratosis, most often of the buccal mucosa, the (lower) lips, and the hard palate, that often turn into erosions and even ulcers. Lesions tend to be symptomless. Involvement of the conjunctival mucosa occurs much less often and may lead to ectropium and scarring (differential diagnoses cicatricial pemphigoid, chlamydial conjunctivitis, and...

Discoid Lupus Erythematosus Lesions of Intermediate

At this stage, central atrophy becomes apparent, and active sectors of the lesion appear as annular or semicircular peripheral erythemas (Fig. 11.1C). DLE lesions of the scalp usually belong to this category (see below). Superficial dermatophytic infections typically present as nummular lesions with raised erythematous, scaly borders and central clearing. Annular and semicircular lesions are often found. In contrast to DLE, there is no atrophy. In adults, superficial mycoses are mainly found in...

Lupus Erythematosus Profundus

LE profundus is a variant of LE described by Kaposi (Kaposi 1883) in 1883 and in more detail by Irgang in 1940 (Irgang 1940). LE profundus is a panniculitis, also termed lupus panniculitis. Clinically, LE profundus has a predilection for the face, neck, proximal extremities, trunk, and lower back (Tuffanelli 1985). Histologically, the epidermis and dermis may be involved, with vacuolar degeneration and dermal lymphocytic infiltration (Fig. 21.3). However, the key feature is the prominent...

Dermatosurgical and Laser Therapy in Cutaneous Lupus Erythematosus

In patients with treatment-resistant lesions, different surgical techniques may offer additional alternatives. For many years, cryotherapy has been used to treat LE lesions however, systematic studies are lacking, and the reported numbers in treatment series are low (Ting and Sontheimer 2001). Further surgical techniques that have been reported in individual cases include dermabrasion, laser resurfacing, hair transplantation, and surgical excision of disfiguring lesions. Owing to the...

Of Cutaneous Lupus Erythematosus

The cutaneous manifestations of lupus erythematosus (LE) are notoriously diverse and may mimic a broad range of unrelated skin disorders, although many of its skin symptoms are straightforward and pose few diagnostic problems. Clinical differential diagnosis has a place in directing the dermatologist toward the correct diagnosis in the primary screening process. This chapter summarizes the diagnostic considerations at this point, before additional diagnostic procedures are carried out. Of...

Chilblain Lupus Erythematosus

CHLE, a rare manifestation of CCLE distinguished by Hutchinson in 1888 (Hutchinson 1888), is strongly influenced by environmental factors (Breathnach and Wells 1979, Doutre et al. 1992, Helm and Jones 2002, Rowell 1987, Uter et al. 1988). This subtype seems to be more frequent in women and, interestingly, very uncommon in the United States, as Tuffanelli and Dubois (Tuffanelli and Dubois 1964) failed to detect such lesions among 520 patients however, these patients were collected for the most...

Typical Laboratory Findings

As in idiopathic lupus, antinuclear antibodies (ANAs) are almost always present, and the pattern is usually homogenous. Although antibodies against single-stranded DNA are common, unlike idiopathic lupus, antibodies against double-stranded DNA are uncommon. Antihistone antibodies are classic (Fritzler and Tan 1978) however, they are not diagnostic because they are often present in idiopathic lupus, and the exact specificity is even different for lupus caused by different drugs (Burlingame and...

Lupus Erythematosus and Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) can occur in patients with all subtypes of the spectrum of LE (Moshella 1989). This association has been reported in patients with DLE (Wheatherhead and Adam 1985), SLE, and SCLE (Callen and Ross 1981, Cram et al. 1973). This fact is well known, and the first cases with this association appeared in the early 1960s. Unfortunately, not all of the cases have been investigated using modern immunologic studies, and these cases cannot be specified well. The study by...

Plasmapheresis and Immunoadsorption

Impaired clearance of immune complexes and the production of autoantibodies are characteristic features of LE. Therefore, it was conceivable that the extracorporal removal of these proteins may help improve LE lesions or support current treatments. Plasmapheresis is a procedure that separates plasma proteins from whole blood by cell centrifugation techniques or membrane technology. Subsequently, the plasma is replaced by albumin and saline. Usually plasmapheresis is combined with an...

Subacute Cutaneos Lupus Erythematosus Differential Diagnosis

Psoriasis Erythematosus

Subacute CLE (SCLE) is an exanthematic skin condition with a typical clinical appearance (diagnosis can often be made before the presence of Ro SSA antibodies is documented) that is localized at the trunk and the extensor aspects of the upper extremities, more rarely in the face and neck (Sontheimer et al. 1979). Lesions have an intermediate morphology between DLE and SLE they are erythematous flat plaques, much thinner than DLE, with some dry scaling but without adherent scales and...

Lupus Erythematosus and Lichen Planus

LE and lichen planus (LP) possess different clinical and histologic pictures and immunologic findings. Copeman et al. (Copeman et al. 1970) reported first in 1970 the coexistence of both diseases in four patients. Additionally, several cases of the coexistence of both diseases have been reported (Baumann 1997, Camisa et al. 1984, Davies et al. 1977, Dimitrova et al. 1982, Piamphongsant et al. 1978, Plotnick and Burnham 1986, Razzaque et al. 1982, Romero et al. 1977). Most of the reported cases...

Psoriasis and Lupus Erythematosus

The coincidence of LE and psoriasis seems to be rare. Based on their prevalence in the population, the coexistence of psoriasis with all forms of lupus seems to be less than expected. Dubois (Dubois 1974) reported that 0.6 of 520 patients with systemic LE (SLE) had concurrent psoriasis. Tumarkin et al. (Tumarkin et al. 1971) described 637 patients with discoid LE (DLE), and only 1 had coexistent psoriasis. In 1927, O'Leary (O'Leary 1927) described one of the first cases of coexistent psoriasis...

Lupus Erythematosus and Alopecia Areata

Diffuse alopecia and especially frontal alopecia due to increased hair fragility is more typical for SLE. Scarring alopecia is a frequent clinical feature of DLE and SLE. Alopecia areata is rarely associated with LE. In a large study of 736 patients with alopecia areata, only 2 had DLE and 2 had SLE (Muller and Winkelmann 1963). In 1975, Lerchin et al. (Lerchin et al. 1975) reported a single case of DLE associated with alopecia areata. Werth et al. (Werth et al. 1992) found 4 patients with...

Subsets of Systemic Lupus Erythematosus

In the wide spectrum of clinical manifestations, different subsets of systemic lupus and clusters can be defined by clinical or serologic items. Relevant and established Table 13.3. Typical autoantibodies in patients with systemic lupus erythematosus (SLE) Table 13.3. Typical autoantibodies in patients with systemic lupus erythematosus (SLE) Anti-double-stranded DNA is disease specific, anti-single-stranded DNA is not high titers are associated with clinical activity Protein complexed to six...

Old burntout Lesions of Discoid Lupus Erythematosus

Long lasting DLE lesions are dominated by atrophy, scarring, and depigmentation. Atrophic scars may be indistinguishable from burnt-out DLE, lacking any signs of inflammation, particularly depigmented scars after superficial third-degree burns. Atrophic acne scars differ by their multiplicity and characteristic distribution. They are not accompanied by pigmentary changes in white skin. The characteristically depressed scars after cutaneous leishmaniosis, in contrast, are hyperpigmented. In all...

During Tolerizing Apoptosis

Apoptosis Lupus

The noninflammatory, tolerance-inducing forms of apoptosis that typify developmental and homeostatic situations generate a highly stereotyped form of death, both morphologically and biochemically Hengartner 2000 . This final common death pathway in this form of tolerance-inducing death is mediated by a family of highly specific death proteases caspases , which operate in an autoamplifying cascade that can be activated by numerous upstream signals Thornberry and Lazebnik 1998 . Recent studies...

Bullous Lesions

Bullous lesions occur infrequently in patients with SLE. Blister formation may develop in some lupus lesions, especially at the periphery. This is generally associated with the presence of anti-Ro SSA antibodies. On rare occasions, blister formation, in all probability an extension of the microscopic separation at the dermal-epidermal junction, may become very extensive, especially in anti-Ro SSA antibody-positive photosensitive patients with SLE, producing cutaneous manifestations similar to...

Prognosis of Rare Variants of Cutaneous Lupus Erythematosus

A few studies have been reported concerning the disease courses in rare CLE variants. LE profundus panniculitis is regarded to have a more benign prognosis than SLE. In 10 years of follow-up, only 4 25 of 16 patients were classified as having SLE according to ARA criteria Watanabe and Tsuchida 1996 . In other case series, only 4 of 40 patients fulfilled the criteria for SLE. The major morbidity in this series resulted from disfigurement and occasional disability related to pain 7 18 of 40...

Photosensitivity in Lupus Erythematosus12

Photosensitivity is a characteristic feature of all forms and subsets of lupus erythematosus LE that has been recognized since the first phenomenologic descriptions of this complex disease. In 1881, Cazenave Cazenave 1881 described exacerbations of the disease related to cold, heat, fire, and direct action of the air, and Hutchinson Hutchinson 1888 reported in 1888 that patients with LE did not tolerate the sun well. At the beginning of the 19th century, several physicians had already realized...

Nonspecific Skin Lesions in Patients with Systemic Lupus Erythematosus

A spectrum of other skin symptoms that are not LE proper may accompany SLE. By definition, these lesions can be found in other diseases as well, but they do have diagnostic significance. Vascular lesions play a dominant role. Raynaud's phenomenon occurs frequently in SLE, as it does in other collagen vascular diseases. Leukocytoclastic vasculitis may arise, often associated with periods of increased disease activity it may present as cutaneous necrotizing vasculitis palpable purpura or as...

UV Irradiation Induces Apoptosis of Keratinocytes and Clustering of Lupus Autoantigens in Apoptotic Surface Blebs

Because the epidermis is one of the physiologic targets of the immunopathologic response in lupus, several groups have established an in vitro epidermal model to address the fate of autoantigens in keratinocytes after irradiation with UVB Casci-ola-Rosen et al. 1994, Furukawa et al. 1990,Golan et al. 1992,LeFeber et al. 1984,Natali and Tan 1973 . One of the striking observations made was that several lupus autoantigens including Ro SSA, La SSB, snRNP, and Sm that are normally intracellular...

UV Light Apoptosis and Autoimmunity

The link between photosensitivity and the induction of autoimmune disease can be understood through a model centered on the apoptotic cell. Apoptosis is a process of programmed cell death during which intracellular antigens are translocated to the cell surface, allowing for detection by the immune system Casciola-Rosen and Rosen 1997, Casciola-Rosen et al. 1994, 1995, 1999, Schultz and Harrington 2003 . Because apoptosis is required for the development and maintenance of tissue homeostasis in...

Differential Diagnosis at Particular Sites Discoid Lupus Erythematosus of the Scalp

Scutula Favus

DLE of the scalp Fig. 11.2A typically arises as one or a few roundish erythematous plaques identical to DLE lesions elsewhere on the skin. When atrophy develops, they gradually transform into patches of scarring alopecia that may be surrounded by rims of scaly erythema. In the early phase, it must be distinguished from psoriasis and seborrheic dermatitis see previously herein . In advanced stages, DLE may Fig. 11.2. A Atrophic alopecia in discoid lupus erythematosus. Note the widened...

Neonatal Lupus Erythematosus

Anti Antila

NLE is a rare disease presenting in the neonatal period that resolves in the first 6 months of life. Associated disorders include transient thrombocytopenia, leukopenia, and a congenital heart block. Affected are children of mothers suffering from SLE. Clinically, children exhibit lesions as seen in SCLE. The causative agents are maternal IgG antinuclear antibodies usually anti-Ro SSA, less frequently anti-La SSB, a-fodrin, and U1-RNP . Histologic changes are similar to those of SCLE. However,...

Livedo Reticularis

In recent years, it has been recognized that livedo reticularis is the manifestation of the presence of antiphospholipid antibodies in patients with SLE secondary antiphospholipid syndrome APS . One study indicates that 17 of 66 patients with SLE demonstrated the presence of livedo reticularis and that 81 of these patients demonstrated the presence of antiphospholipid antibodies Yasue 1986 . The APS can also occur in the absence of evidence of SLE and is termed primary APS. Patients with SLE...

Butterfly Rash

Lupus Rash Nasolabial Lines

The butterfly rash or malar rash, a proverbial diagnostic lesion of SLE, is most often seen in early SLE Dubois et al. 1964 . It is composed of at least partially well- Fig. 11.4. A Butterfly rash in systemic lupus erythematosus. A well-demarcated, symmetrical erythema of the malar areas and the back of the nose that has progressed to the forehead and perioral skin. Note the sparing of the nasolabial folds. B Seborrheic dermatitis note the yellowish color and involvement of the nasolabial folds...

Erythematosus

The clinical expression of skin involvement in patients with lupus erythematosus LE is very common and shows great variation. Therefore, it has been difficult to develop a unifying concept of the cutaneous manifestations of this disease, and much attention has been paid to the issue of classifying LE from the dermatologic perspective in the past. However, the only universally accepted criteria for the classification of LE are those of the American Rheumatism Association ARA , now known as the...

Perniosis Chilblains

Perniosis is an inflammatory disease process commonly occurring in patients living in cold, damp geographical regions. It typically consists of erythematous papules involving the fingers, toes, nose, or ears. In general, most cases resolve within a few days and are not related to SLE. However, some lesions persist and demonstrate blister or ulcer formation. French investigators have determined that one third of the patients with chilblain lupus having this disease process for greater than 1...

Discoid Lupus Erythematosus of the Palms and Soles

DLE of the palms and soles is a rare occurrence characterized by sharply demarcated erythemas and adherent scaling the lesions tend to be painful and may become erosive. Atrophy and scarring are the features that allow a distinction from the following Palmoplantarpsoriasis has no signs of atrophy. Note that palmoplantar psoriasis is only rarely an isolated finding. Keratoderma blennorhagicum in patients with Reiter's disease presents with pso-riasiform palmoplantar lesions composed of...

Erythema Multiforme and Lupus Erythematosus Rowells Syndrome

Rowell et al. 1963 described four patients with the clinical picture of chronic DLE associated with erythema multiforme EM . Besides the skin changes compatible with both diseases, the patients had characteristic immunologic findings consisting of the speckled type of ANAs, the anti-SjT type of precipitating antibody to saline extract of human tissues and rheumatoid factor. In some patients, perniotic-like lesions were also observed. Later it turned out that SjT is...

CAMs in Cutaneous Lupus Erythematosus

Figurate Erythema Dermatology

Different patterns of ICAM-1 expression in the epidermis have been documented in LE vs other cutaneous inflammation and also between subsets of LE. In experimentally UVA- and UVB-induced lesions in patients with LE and PLE, those with SCLE showed ICAM-1 expression throughout the epidermis, those with DLE showed basal ICAM-1 staining, and those with PLE showed focal basal ICAM-1 staining associated with lymphocyte infiltrates Stephansson and Ros 1993 . SCLE, erythema multiforme, and lichen...

References

O'Leary PA 1934 Disseminated lupus erythematosus. Minn Med 17 637-644 Baer RL, Harber LC 1965 Photobiology of lupus erythematosus. Arch Dermatol 92 124-128 Brocq L 1921 Precis-atlas de pratique dermatologique. G Doin, Paris, pp 468-477 Casciola-Rosen LA, Anhalt G, Rosen A 1994 Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 179 1317-1330 Cazenave PLA 1851 Lupus erythemateux erytheme centrifuge...

Acute Cutaneous Lupus Erythematosus

Transient Maculopapular Butterfly Rash

The typical clinical manifestations of ACLE are characterized by a localized erythema known as the malar rash or butterfly rash on the central portion of the face or by a generalized, more widespread form Fabbri et al. 2003, Sontheimer and Provost 2003 . Localized ACLE may only affect the skin transiently, and the lesions may last for only several days up to a few weeks. Therefore, at the onset of disease, the patients may mistake this rash for sunburn and may seek medical advice only after the...

Bullous Lesions in Lupus Erythematosus

Lupus Tumidus

The frequency of bullous lesions associated with LE BLE is low, and it has been reported that less than 5 of patients with SLE and skin changes had chronic vesicu-lobullous lesions Gammon and Briggaman 1993, Yell and Wojnarowska 1997 . Confusion has always existed concerning the nosology and classification of the bullous skin changes that can occur in patients with LE, and there has been no consensus in this area for a long time. In 1997, Sontheimer Sontheimer 1997 divided the various types of...

Discoid Lupus Erythematosus

Discoid Lip

The most common form of all chronic cutaneous variants is DLE, which can be localized or generalized, both with and without systemic manifestations of LE. Typical DLE lesions may be present at the onset of SLE in about 5 -10 of patients, and approximately 30 of patients may develop DLE lesions, usually of the generalized type, during the course of SLE Cervera et al. 1993,Hymes and Jordon 1989,Tebbe et al. 1997 . The localized form presents with sharply demarcated, erythematokeratotic, atrophic...