The manifestations of LET consist of erythematous papules, plaques, or annular lesions with a succulent appearance; lesions develop mainly on sun-exposed areas such as the neckline, shoulders, face, and arms. The features that differentiate LET lesions from those of DLE and SCLE are the absence of desquamation, follicular plugs, or atrophy (Figs. 1–3); in addition, they heal without leaving a scar or hypopigmentation.9–12,14–16 The lesions tend to appear in crops, almost always related to exposure to the sun, mainly during the spring and summer. It is important determine the course of lesions after exposure to the sun, as this helps to differentiate LET from polymorphous light eruption. In LET, the lesions do not appear immediately, but rather after a latency period that varies between 24hours and several weeks.11,12,17,18 Moreover, they tend to persist throughout the summer and even into the autumn. Below, we look in detail at certain aspects of photosensitivity in LET and the possible etiological and pathogenic factors involved.

Figure 1.

Characteristic lesions of lupus erythematosus tumidus on the neck.

(0.07MB).

Figure 2.

Characteristic lesions of lupus erythematosus tumidus on the face.

(0.07MB).

Figure 3.

Characteristic lesions of lupus erythematosus tumidus on the back.

(0.07MB).

Another distinctive feature of LET is that it is rarely associated with antinuclear (ANA), anti-Ro, anti-La, or anti-DNA antibodies.9–12,14–16 Blood tests also show few alterations, and it is uncommon to observe cytopenias or abnormalities of renal function. These findings, together with the low frequency of the systemic complications typical of systemic lupus erythematosus (SLE), indicate that the systemic behavior of LET is very similar to that of DLE.

LET is characterized by marked photosensitivity, and this has been demonstrated experimentally in a number of photobiological studies. Based on that research, LET is considered to be the most photosensitive form of CLE, more so even than SCLE. In LET, 70% to 76% of lesions are photoinduced,11,15,17,18 a higher proportion than in SCLE (62% to 63%).11,17 For many years, photosensitivity in CLE has been considered to be very closely linked to the presence of autoantibodies in the blood, principally anti-Ro antibodies.19,20 Although no direct relationship has been demonstrated in vivo between photosensitivity and the presence of these antibodies,21 their involvement in at least some types of lupus erythematosus appears very likely. Another suggestive finding that supports this theory is the appearance of skin lesions in neonatal lupus linked to the presence in the infant's blood of anti-Ro antibodies passed from the mother.22

However, the marked photosensitivity of LET, a disease not typically associated with the presence of ANA, anti-Ro antibodies, or anti-La antibodies in the blood, means that we must consider alternative mechanisms that might give rise to these lesions. The results of recent research point to the involvement of a particular cell type, the plasmacytoid dendritic cells (PDC) and their product, type I interferons (IFNs α and β), as a key elements in the etiology and pathogenesis of the lesions of lupus. Their presence has been demonstrated in biopsies of the skin lesions of SLE,23–26 SCLE, and DLE,23–25,27 as well as in those of LET.23,27–29 IFN-α, together with IFN-γ produced by T lymphocytes, induces the production of a series of chemokines (CXCL 9, 10, and 11) by the structural cells of the skin (keratinocytes, endothelial cells, and fibroblasts); these chemokines, in turn, attract more T lymphocytes and PDCs. This thus sets up a positive feedback loop that amplifies the inflammatory response.23 The mechanism of activation of these PDCs is still not fully understood, but it could have its origin in cell apoptosis caused by UV radiation and the subsequent exposure of autologous DNA. In patients with SLE it has been suggested that this autologous DNA could bind autoantibodies, giving rise to immune complexes that are captured by the PDCs and activate an intracellular receptor.30 However, this mechanism cannot be extrapolated to the forms of CLE that are not associated with autoantibodies in the blood, such as DLE and LET.31 In these 2 diseases, the mechanism of activation of the PDCs could be similar to the one described by Lande et al32 in psoriasis. Those authors identified an antimicrobial peptide called LL37 that binds with autologous DNA to form complexes that are then taken up by the PDCs and trigger Toll-like receptor 9.

The lesions triggered by exposure to sunlight in LET could therefore arise when certain peptides bind to autologous DNA and form complexes that activate the PDCs, thus inducing the production of type I interferon. However, this hypothesis has not yet been confirmed.

Although most authors agree on the clinical features and prognosis of LET, there is still debate about the histopathological features. There is consensus on the microscopic findings in the dermis, where a periadnexal and perivascular lymphocytic infiltrate is observed with interstitial mucin deposits, and several studies have reported that direct immunofluorescence does not usually reveal significant immunoglobulin or complement deposition on the basement membrane.10–12,14,16,33 There are, however, different opinions on the changes in the epidermis. According to Kuhn et al,12,33 the epidermis is intact in practically all cases, and this finding has been confirmed in other studies11,16 (Fig. 4). However, recent research has demonstrated that mild epidermal alterations, including focal vacuolization of the basal layer, hyperkeratosis, and follicular atrophy or plugging, are observed in 61% to 70% of cases; specifically, vacuolization of the basal layer is observed in 19% to 46% of biopsies.10,14 In their description of the papular lesions that we may now classify as LET, McHugh et al8 reported that biopsies from 1 group of patients presented the typical epidermal alterations of lupus, whereas in the remaining cases the epidermis was intact. In our opinion, the findings of those authors may be closer to the true picture since it is not rare in practice to encounter patients who have lesions typical of LET in whom a biopsy reveals epidermal changes. Consensus on this matter and greater definition are important because of its implications in the diagnosis of LET.

Figure 4.

Biopsy of lupus erythematosus tumidus showing a perivascular and periadnexal lymphocytic infiltrate with interstitial mucin deposits and no alterations of the epidermis (photograph supplied by Dr. M.T. Fernández-Figueras) (Hematoxylin-eosin, original magnification x40).

(1.07MB).

The diversity of opinions regarding the epidermal features of LET on light microscopy has given rise to different proposals for the diagnostic criteria of this disease; the key differences between these proposals refer to the histopathological appearance. In 2002, Kuhn et al12 established criteria that included an absence of alterations of the epidermis or at the dermal-epidermal junction.

In clinical practice, as we have mentioned above, some of the patients presenting the lesions typical of LET do not entirely fit the criteria proposed by Kuhn in that mild or moderate epidermal changes are seen in the biopsy. We therefore consider the diagnostic criteria put forward by Vieira et al10 to be closer to reality. Some later studies also accept mild or focal alterations of the epidermis when making a diagnosis of LET.11,14 In Table 1, the authors present their own adaptation of the diagnostic criteria proposed in previous publications. We have added an item on photosensitivity, which is important not for differentiation from the other forms of CLE, but to distinguish LET from certain photodermatoses, particularly polymorphous light eruption.

In summary, in clinical practice, a suspected diagnosis of LET may be established in a patient with erythematous, infiltrated papules, plaques, or annular lesions that, unlike the lesions observed in DLE or SCLE, do not present superficial alterations such as desquamation, atrophy, or erosions. The diagnosis is confirmed by biopsy showing an absence of epidermal alterations or a mild form of the epidermal changes typical of lupus erythematosus, a periadnexal and perivascular lymphocytic infiltrate, and interstitial mucin deposits in the context of a patient who, in general, does not present systemic manifestations of SLE and does not have autoantibodies.

This said, there continue to be certain problems in practice when making a diagnosis of LET. The first issue is the subjectivity of defining a mild degree of microscopic alterations of the epidermis or a clinical absence of superficial alterations. Secondly, some patients present the characteristic lesions of LET in association with autoantibodies or with the systemic manifestations of SLE,16 in which case we must consider the possibility of rare presentations of LET or exclude the diagnosis. Finally, as will be discussed below, the differential diagnosis with other conditions is not always easy.

Some authors have questioned the lupic origin of LET, basing their arguments on the absence of autoantibodies, of any of the systemic manifestations of lupus erythematosus, or of an interface dermatitis in the histology study.34 Those authors consider LET to be a photodermatosis that does not form part of the spectrum of CLE. There is, however, evidence that challenges that assertion. First, as we have seen, a large proportion of cases of LET do present an interface dermatitis.8,10,14 Secondly, as the low frequency of autoantibodies and of systemic manifestations is also observed in DLE, these characteristics are not a solid argument for excluding LET from the spectrum of CLE. It should also be noted that there have been reports of patients with simultaneous lesions of LET and DLE,11,12,16 a finding that supports the view that the two conditions are different forms of the same disease. Finally, the presence of PDCs and proteins induced by IFN-α23,27–29 in the biopsies of LET lesions would suggest a common etiological and pathogenic mechanism with other forms of CLE. Thus, in our opinion, there is sufficient evidence in the literature to consider LET to be a form of lupus erythematosus.

As has been commented above, Gilliam's original classification did not include LET. In successive revisions and modifications of that classification, LET has been included as a subgroup of CCLE (Table 2).35,36 The main reason for this decision is the similarity between LET and CCLE in terms of prognosis and their minimal association with autoantibodies. However, as their clinical features are very different, some authors consider LET to be an independent subtype. Kuhn et al9 suggested that LET should be included as a fourth subtype called intermittent CLE (Table 3). In our opinion, this is a reasonable proposal because the essential characteristic of all the forms of CCLE is the presence of persistent lesions that leave scarring or atrophy, something that does not occur in LET. However, Kuhn et al's proposal has still not been widely accepted, and the most recent review articles continue to situate LET within the CCLE group.36

There are 3 skin conditions that are difficult to differentiate from LET due to their clinical and microscopic similarities: Jessner lymphocytic infiltration, polymorphous light eruption, and reticular erythematous mucinosis.

Jessner lymphocytic infiltration was described in the 1950s by Jessner and Kanof37 as a condition giving rise to nonscarring lesions that mainly affect the face and that present a periadnexal and perivascular lymphocytic infiltrate on light microscopy, without alteration of the epidermis.38 As patients did not show photosensitivity and the condition did not appear to respond to treatment with antimalarials, it was considered not to be lupic in origin. However, some studies published during the following years have cast doubt on these conclusions.39,40 Studies performed in the past decade generally conclude that Jessner lymphocytic infiltration falls within the spectrum of lupus and, in particular, could be considered a form of LET. In a photobiology study in 10 patients with Jessner lymphocytic infiltration, Weber et al41 demonstrated that all the patients developed lesions after photoprovocation and observed a latency period of over 48hours before the appearance of the lesions, as occurs in all forms of CLE. Study of biopsies of the lesions revealed a perivascular and periadnexal infiltrate indistinguishable from LET, with interstitial mucin deposits and an unaltered epidermis. Their findings led them to conclude that there were no significant clinical, pathological, or photobiological differences between Jessner lymphocytic infiltration and LET. Rémy-Leroux et al42 conducted a comparative study of 32 cases of Jessner lymphocytic infiltration and 14 cases of LET. After analyzing the clinical and microscopic features and the response of the 2 groups of patients in the photobiology study, they concluded that Jessner lymphocytic infiltration and LET are indistinguishable. Based on the findings of those studies, Jessner lymphocytic infiltration is now generally considered to be a subtype of LET rather than a separate disease.

Polymorphous light eruption is a photodermatosis that gives rise to a wide variety of skin lesions, although these tend to be monomorphic in any one patient. The lesions may be vesicular or pseudovesicular, or they can take the form of papules or plaques that are difficult to differentiate from LET. In the latter case, certain differences in the clinical course of the lesions are the key to resolving the differential diagnosis. In contrast to LET, the lesions of polymorphous light eruption develop soon after exposure to sunlight and improve within a few days if there is no further exposure. Moreover, the attacks decrease in severity if exposure is maintained, as a very characteristic tolerance phenomenon develops.12 Furthermore, while the lesions in patients with LET typically persist after the summer, episodes of polymorphous light eruption are strictly limited to the spring and summer months. However, it must be said that, in contrast to the situation with Jessner lymphocytic infiltration, there are no clinical or photobiological studies that compare the features of polymorphous light eruption and LET. Microscopically, polymorphous light eruption can also be difficult to differentiate from CLE, as the 2 diseases may share certain common features, such as the perivascular lymphocytic infiltrate, vacuolar changes in the basal layer (that are mild and do not include necrotic keratinocytes), epidermal atrophy, and follicular plugging.43–45 Positive direct immunofluorescence has also been demonstrated in some cases.46 A feature that has come to be considered characteristic of this condition is edema of the papillary dermis. However, a recent study by Pincus et al47 also demonstrated this edema in biopsies from patients with CLE (SCLE and DLE). After reviewing the literature, those authors concluded that the histopathological features that differentiate CLE from polymorphous light eruption are the abundant interstitial mucin deposits, the periadnexal lymphocytic infiltrate, and the intense vacuolar degeneration of the basal layer; in the case of LET, we should focus on the first 2 features. Thus, although LET and polymorphous light eruption may be similar in some aspects, they differ in others, and should be considered to be different diseases. Wackernagel et al29 demonstrated the presence of PDCs in the majority (91%) of biopsies from patients with CLE (including LET, CCLE, and SCLE) and in none of those from patients with polymorphous light eruption, and they concluded that the 2 conditions probably have a different etiology and pathogenesis.

Reticular erythematous mucinosis most often affects young women and typically presents as a reticulated macular or papular erythema. Biopsy of the lesions reveals a periadnexal and perivascular lymphocytic infiltrate associated with interstitial mucin deposits.48 Patients also usually report marked photosensitivity. Because of this, some authors have considered reticular erythematous mucinosis to be a variant of CCLE or LET,12 though it is important to note the finding of immunoglobulin M deposits on the basement membrane in some cases of reticular erythematous mucinosis.49 However, no comparative studies between the 2 conditions that would allow this theory to be confirmed have been published.