Actinic prurigo (AP) is an idiopathic photodermatosis, that develop bilaterally and symmetrically, affecting predominantly areas of the face, neck, trunk, and extremities, particularly on the nasal dorsum, zygomatic arches, lower lip, and conjunctiva.1,2 Since it is extremely pruritic, excoriations, serohematic crusts, areas of lichenification, scars, and residual hypo- or hyperpigmentation appear.1-5
IgE was first discovered in 1966 and later implicated as the mediator of type I hypersensitivity reactions. Quantification of IgE is part of the comprehensive assessment of patients with allergic conditions.6 However, IgE, produced by B cells, is also involved in other subtypes of hypersensitivity reactions (IV b).7
To understand the pathophysiology of AP, we performed this study to examine serum IgE levels in AP and associate them with the clinical manifestation of this disease.
This case-control study was conducted in the Department of Dermatology, at the Dr. Manuel Gea Gonzalez General Hospital, in Mexico City.
We included 21 patients with a clinical diagnosis of AP confirmed by histopathology, as well as 21 clinically healthy subjects who visited the hospital for other reasons - mainly cosmetic-excluding those with other allergic diseases.
Both groups were asked to sign consent forms. Detailed histories were taken, and in the physical examination, 3cc of peripheral blood was drawn for the immunoassay.
Cases were grouped by lesion severity: into mild, moderate, and severe:
Mild: few papular lesions or excoriations on photo-exposed sites.
Moderate: papular lesions, excoriations, and moderate pruritus.
Severe: papules, excoriations, cheilitis, conjunctival disease, and severe pruritus.
The experimental procedures began on completion of the clinical elements of the project.
The 2-step Access Total IgE sandwich assay was performed, in which the sample was added to a reaction vessel with paramagnetic particles that were coated by goat-anti-mouse:anti-mouse IgG complexes.
The reaction vessel was separated by a magnetic field and washed, removing material that was not bound to the solid phase. Alkaline phosphatase-conjugated anti-IgE equine was added and the reaction was separated and washed to remove unbound conjugate.
Lumi-phos* 530 chemiluminescent substrate was added to the reaction, and the light generated was measured on a luminometer (light production was directly proportional to the concentration of IgE in the sample) using the Dχi 800 Access System and Total IgE reagent. The reference range was 1.31-165.3 UI/mL. The variable was dichotomized (normal and elevated levels of IgE) between cases and healthy subjects, and the groups were homogeneous by χ2 test.
The database and statistical analysis was performed using SPSS, version 20 (Chicago, IL, USA).
Of the 21 patients with a confirmed diagnosis of AP, 13 (62%) were female and 8 (38%) were male. The mean age was 26.86 years (range 7-47). Sixteen of the 21 controls (76%) were women.
Eleven (52.3%) AP patients had elevated serum levels of IgE, of whom 9 (82%) were women. Ten of the patients with high serum levels (91%) were being treated with thalidomide, and 1 (9%) was on topical steroids. Table 1 shows the IgE levels of cases and controls, while tables 2 and 3 list their clinical profiles and relationship with IgE levels.
|Patient||Age||Sex||Clinical picture||Treatment||IgE level|
*Elevated serum levels of IgE, reference ranges (1.31-165.3 UI/mL)
Twenty-one controls (100%) and 10 AP patients (47.7%) had low serum IgE levels (maximum 80 U / ml).
Six (54.5%) AP patients with elevated serum IgE levels had moderate injuries, 4 (36.4%) had severe injuries, and 1 (9.1%) had minor injuries.
At the time of the clinical evaluation, 8 (80%) patients with normal levels of IgE had minor injury, 1 (10%) had moderate injury, and the remainder (10%) had no lesions.
It has been suggested that the pathophysiology of AP involves a type IV subtype a-b hypersensitivity response.8 Hypersensitivity reactions are exaggerated immune responses against environmental antigens.9 In 2013, Vera et al. reported that AP patients were exposed to antigens which could trigger an allergic response, notably wood smoke and cohabitation with pets or farm animals.10 Nevertheless, other antigens that trigger the inflammatory process which causes the development of mucocutaneous lesions should be identified.
The type IV response is mediated by T lymphocytes and their soluble products in which lymphocytes that sensitized and induced to produce cytokines are recruited.9 The subtype b response corresponds to a Th2 reaction, whereby IL4, IL13, and IL5 are secreted and B cell, IgE, and IgG4 production is promoted, with the subsequent deactivation of macrophages and participation of mast cells and eosinophils.7
Our findings complement those of Martínez et al., who identified mast cells and eosinophils in AP lesions of the lip and skin.11
Notably, patients with moderate to severe lesions had elevated IgE levels, contrasting with the normal serum levels in those with minor injuries. No difference was observed between the presence and severity of injury and treatment; 2 patients were not undergoing treatment with thalidomide - 1 had high IgE levels, the other had normal levels. These variables should be examined in greater detail.
The involvement of TNF-alpha, the presence of apoptosis, and NK cell activation by IL2 remain to be addressed. In addition, we must determine if AP patients are exposed to various antigens that trigger the disease or whether ultraviolet light is the sole causative factor.