Jessner's lymphocytic infiltrate

INTRODUCTION — Jessner's lymphocytic infiltrate (JLI), also called benign lymphocytic infiltration of the skin, is a rare, benign dermatosis with a self-limiting course and an excellent prognosis. It typically presents as erythematous papules and plaques primarily located on the face, neck, or upper back.

However, since the original description by Jessner and Kanof in 1953 [1], the existence of JLI as a distinct disease has been questioned [2]. The list of disorders that overlap clinically and histologically with JLI is vast, indicating that JLI is probably not a separate entity, but rather a clinicopathologic reaction pattern common to different skin diseases [2-8].

In the last few decades, significant advancements in the immunopathologic and molecular diagnosis have enabled a specific diagnosis for many of the cases previously labeled as JLI [8-10]. Nonetheless, some cases of JLI defy a precise diagnosis.

This topic will review the clinical manifestations, diagnosis, differential diagnosis, and management of JLI. Other benign lymphoproliferative skin disorders are discussed separately. (See "Cutaneous T cell pseudolymphomas" and "Cutaneous B cell pseudolymphoma".)

EPIDEMIOLOGY — JLI is rare. Its incidence and prevalence are unknown. JLI usually occurs in older adults, without sex predilection [2]. It is very rare in children, with only a few cases reported in the literature [11,12]. There is no sex or racial predominance.

PATHOGENESIS — The etiology and pathophysiology of JLI are not well understood. Some believe JLI to be a variant of lupus tumidus, a rare subtype of chronic cutaneous lupus erythematosus, or a plaque-type polymorphous light eruption (PMLE) [10]. (See "Tumid lupus erythematosus" and "Polymorphous light eruption".)

Drug-induced cases of JLI have also been described [13-17]. There are single case reports of JLI induced by ustekinumab [18] and etanercept [19]. JLI has also been reported in association with cutaneous B cell lymphomas [20] and immune reconstitution syndrome in human immunodeficiency virus (HIV) [21].

CLINICAL MANIFESTATIONS — JLI presents as persistent, erythematous papules or plaques typically located in the sun-exposed areas, predominantly in the malar region of the face (picture 1A-B) and on the upper back [10,15]. Lesions usually range from several millimeters to several centimeters, may be single or multiple, and are sometimes arranged in an annular or circinate pattern. There are no epidermal changes such as scaling, atrophy, or scarring.

Local or systemic symptoms are usually absent, but burning and pruritus have been occasionally reported. JLI has a chronic waxing and waning course without long-term sequelae [7]. Sun exposure may induce exacerbation of the skin lesions in some patients.

Immunohistochemistry demonstrates an infiltrate consisting predominantly of reactive CD8⁺ T cells, with a few CD4⁺ T cells and B cells [7]. Small clusters of plasmacytoid dendritic cells have been described in JLI as well as in lupus erythematosus tumidus (LET) [5]. T cell receptor (TCR)-gamma gene rearrangement analysis demonstrates a polyclonal T cell population in the majority of cases [7].

PATHOLOGY — Histopathologic examination of JLI shows a normal epidermis without evidence of atrophy, interface changes, or follicular plugging. There is a moderately dense superficial and deep perivascular lymphocytic infiltrate with bland, normal-appearing, mature lymphocytes, which may be deep and involve the subcutis [10]. Mild mucin deposition may be seen in the papillary and reticular dermis. Unlike polymorphous light eruption (PMLE), there is no papillary edema. Direct immunofluorescence is negative.

DIAGNOSIS — The clinical and histologic features of JLI largely overlap with other skin diseases, primarily lupus erythematosus tumidus (LET), polymorphous light eruption (PMLE), and cutaneous lymphoid hyperplasia (see 'Differential diagnosis' below). Thus, the diagnosis of JLI in a patient presenting with asymptomatic persistent, erythematous papules or plaques on of the face (picture 1A-B) or on the upper back is one of exclusion and should be limited to the rare cases that defy a specific diagnosis after extensive diagnostic work-up, which includes:

●History – The patient should be questioned about the onset and course of the skin lesions (eg, seasonal variation, exacerbation with sun exposure), presence of associated local or systemic symptoms, exposure to arthropod bites, and medication history. Seasonal variations may point towards conditions such as PMLE or lupus, which are associated with sensitivity to sunlight and may be exacerbated during summer months. Presence of any systemic symptoms may suggest looking into systemic lupus erythematosus. Arthropod bites and certain medications may be associated with pseudolymphomas or cutaneous lymphoid hyperplasia.

●Skin biopsy – A skin biopsy (punch or excisional) of a fresh lesion that has not been treated with topical corticosteroids for at least two weeks should be performed for routine hematoxylin and eosin (H&E). Immunohistochemical and immunofluorescence staining and molecular studies may be needed for accurate diagnosis and to guide therapy choices. In difficult cases, repeated skin biopsies may be necessary for a definitive diagnosis.

●Laboratory tests – Serologic testing may include antinuclear antibodies in patients with suspected systemic lupus erythematosus and antibodies to Borrelia burgdorferi in patients living in endemic areas for Lyme disease and suspected to have cutaneous lymphoid hyperplasia. (See "Measurement and clinical significance of antinuclear antibodies" and "Diagnosis of Lyme disease" and 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The main differential diagnoses of JLI include lupus erythematosus tumidus (LET), polymorphous light eruption (PMLE), and cutaneous lymphoid hyperplasia. These conditions share clinical and histopathologic features and, in some cases, may be extremely difficult to differentiate from each other.

Lupus erythematosus tumidus — LET is a photosensitive dermatosis presenting with red-violaceous urticarial or edematous plaques or nodules in sun-exposed areas (picture 2A-B). LET is considered a separate entity in the spectrum of cutaneous lupus erythematosus [22,23]. Differentiating LET from JLI may be difficult or impossible, given the extensive overlap of clinical and pathologic features between the two conditions [2]. On histology, both conditions show a normal epidermis and lack of scale and follicular plugging. However, LET is characterized by abundant mucin deposition and, in approximately one-half of the cases, presents mild epidermal alterations and focal basal vacuolization [24]. Direct immunofluorescence in tumid lupus is often negative or nonspecific, but when it is positive, it has a characteristic granular immunoglobulin G (IgG) and/or immunoglobulin M (IgM) deposition at the dermal-epidermal junction and around hair follicles. A minority of patients with LET may have a positive test for antinuclear antibodies. (See "Tumid lupus erythematosus".)

Polymorphous light reaction — PMLE is the most common idiopathic photodermatosis. It presents as pruritic papule, or plaques that appear hours or days after sun exposure and persist for days (picture 3). Histology shows focal epidermal spongiosis with lymphocyte exocytosis and a perivascular and periadnexal lymphohistiocytic infiltrate with occasional plasma cells. Papillary dermal edema and interface changes can be seen in PMLE, but are usually absent in JLI. A positive provocative phototest may be an additional support for the diagnosis of PMLE. (See "Polymorphous light eruption".)

Cutaneous lymphoid hyperplasia — Cutaneous lymphoid hyperplasia, also called cutaneous B cell pseudolymphoma or borrelial lymphocytoma cutis, is a rare reactive B cell proliferation response to a variety of antigenic stimuli. It presents as a skin-colored or red solitary nodule or plaque, preferentially located on the face or chest (picture 4A-B). On histology, there are nodular or diffuse mixed-cellular infiltrates throughout the entire dermis, often with formation of lymphoid follicles. In contrast, in JLI, the infiltrate is predominantly perivascular, and reactive B cell follicles are absent. If the clinical presentation and patient history (eg, exposure to tick bites, living in or having traveled to an endemic area for Lyme disease) is suggestive of borrelial lymphocytoma cutis, laboratory testing for confirmation of borreliosis is recommended. (See "Cutaneous B cell pseudolymphoma" and "Diagnosis of Lyme disease".)

Cutaneous lymphomas — Primary cutaneous follicle center lymphoma (PCFCL) presents as solitary or grouped erythematous, asymptomatic papules, plaques, or tumors with a predilection for the scalp, forehead, neck, and trunk that can mimic inflammatory lesions, including cutaneous lymphoid hyperplasia and JLI. Histopathologic examination shows an epidermis-sparing B cell infiltrate composed of centrocytes and centroblasts with a follicular or diffuse pattern. Immunoglobulin gene rearrangement analysis demonstrates B cell clonality. (See "Primary cutaneous follicle center lymphoma" and "Primary cutaneous marginal zone lymphoma".)

Cutaneous T cell lymphoma (CTCL) usually presents with persistent or progressive erythematous patches or plaques, often located in nonexposed skin areas. Histologic, immunophenotypic, and molecular features that support the diagnosis of CTCL include the presence of epidermotropism and lymphoid atypia, lack of markers of mature T cells (CD2, CD3, CD5, and CD7), and clonal T cell receptor rearrangement. (See "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides".)

Granuloma faciale — Granuloma faciale is a rare inflammatory disorder of the skin presenting as red-brown or violaceous papules, plaques, or nodules most commonly located on the face (picture 5). Histologic examination reveals a mixed inflammatory infiltrate in the dermis with neutrophils, eosinophils, histiocytes, and plasma cells. (See "Granuloma faciale".)

TREATMENT — JLI is a benign process with a self-limiting course. Although lesions are usually asymptomatic, patients with facial lesions resulting in cosmetic disfigurement may require treatment.

Multiple therapies have been used for the treatment of JLI, including topical and intralesional corticosteroids [25], topical calcineurin inhibitors [26], oral auranofin [27], oral antimalarials, oral thalidomide [28,29], single-agent chemotherapy [30,31], pulsed dye laser (PDL) [32,33], and photodynamic therapy (PDT) [34]. However, data on their efficacy are scarce and mainly derived from individual case reports or very small case series with a short follow-up.

In patients in whom a complete diagnostic work-up is inconclusive and a tentative diagnosis of JLI is made, it is reasonable to start treatment with the least harmful modalities, such as a short course of potent or ultra-potent topical corticosteroid (groups 1 to 3 (table 1)) or intralesional corticosteroids (eg, triamcinolone acetonide 10 mg/mL).

There are no established regimens for any of the systemic agents in JLI. Considering the benign and self-limiting nature of JLI, a decision to use a systemic agent (eg, antimalarials, thalidomide, methotrexate) for refractory JLI should be made on a case-by-case basis. Light or laser therapy should be used with caution in patients in whom an underlying lupus diagnosis cannot be excluded [35]. Photoprotection is advised for patients reporting photosensitivity.

PROGNOSIS AND FOLLOW-UP — JLI is a benign, self-limiting disorder with an excellent prognosis [2]. However, given its prolonged course (sometimes years) and the controversy surrounding the JLI diagnosis, a semi-annual re-evaluation, with repeated biopsies and laboratory tests as needed, is appropriate for most patients.

SUMMARY AND RECOMMENDATIONS

●Definition – Jessner's lymphocytic infiltrate (JLI) is a benign dermatosis with a self-limiting course and excellent prognosis. However, whether JLI is a distinct entity or a clinicopathologic reaction pattern common to different skin diseases is still matter of debate. (See 'Introduction' above.)

●Clinical presentation – JLI presents as erythematous papules or plaques located in the sun-exposed areas. Lesions may be single or multiple, the latter sometimes arranged in an annular or circinate pattern (picture 1A-B). (See 'Clinical manifestations' above.)

●Diagnosis – The diagnosis of JLI is one of exclusion and is based upon review of clinical and histologic findings. Histology shows a dense perivascular lymphocytic infiltrate of normal-appearing, mature CD8⁺ T lymphocytes. Direct immunofluorescence is usually negative. (See 'Diagnosis' above and 'Pathology' above.)

●Differential diagnosis – The differential diagnosis of JLI includes primarily lupus erythematosus tumidus (LET), polymorphous light eruption (PMLE), and cutaneous lymphoid hyperplasia (borrelial lymphocytoma cutis). (See 'Differential diagnosis' above.)

●Treatment – JLI is a benign process with a self-limiting course and may not require treatment. For patients who have symptomatic lesions or lesions located on cosmetically sensitive areas, topical or intralesional corticosteroids can be used as initial treatment. (See 'Treatment' above.)