RESUMEN
BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.
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Síndrome de Stevens-Johnson , Adulto , Niño , Consenso , Humanos , Investigación , Estudios Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapiaRESUMEN
Although numerous infective agents, including varicella zoster virus (VZV), have been described in association with pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC), none has been identified consistently in these lesions. We sought to immunohistochemically identify VZV glycoprotein (g)E antigens in the vascular endothelium in PLEVA and PLC lesions, based on our previous observation that gE was detected in the vascular endothelium and eccrine unit up until 2 months and 2.5, respectively, years after herpes zoster (HZ) infection. In five of the six cases of PLEVA, VZV gE was identified in the endothelial cells and eccrine epithelium, as observed in HZ lesions, whereas VZV gE was detected in only one of seven patients with PLC. None of the patients with PLEVA who had VZV gE-positive vascular endothelial cells had experienced previous episodes of HZ. VZV may be one of the aetiological agents for PLEVA while other aetiological factors could exist in PLC.
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Herpesvirus Humano 3/aislamiento & purificación , Pitiriasis Liquenoide/virología , Infección por el Virus de la Varicela-Zóster/complicaciones , Adolescente , Adulto , Femenino , Humanos , Masculino , Pitiriasis Liquenoide/patología , Estudios Retrospectivos , Proteínas del Envoltorio Viral/aislamiento & purificaciónRESUMEN
BACKGROUND: Although a number of pathological processes resulting in amyloid deposition have been described in lichen amyloidosus (LA), no attention has been paid to the involvement of sweat glands/ducts in the pathogenesis of LA. According to recent studies, follicular structures are usually spared in serial histological sections of LA, and deposits of amyloid are likely to be confined to areas that display xerosis, suggesting that decreases in skin wetness by sweating disturbance seem to initiate LA. OBJECTIVES: To investigate whether sweating disturbance could represent an early event that triggers LA, and whether resolution of LA could be induced by restoring the sweating disturbance. METHODS: By using the impression mould technique, which allows an accurate quantification of individual sweat glands/ducts actively delivering sweat, we examined sweat responses to thermal stimulus in LA lesions before and after treatment with a moisturizer. RESULTS: Sweating disturbance was most profoundly detected in the 'hub' structure of the LA papule, and this disturbance due to leakage of sweat could be restored by short-term treatment with a moisturizer, particularly when used under occlusion. CONCLUSIONS: This study was limited by the relatively small sample size. Treatment of LA should be primarily directed at preventing leakage of sweat into the dermis or epidermis and therefore sweat delivery to the skin surface could be made easier.
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Amiloidosis/etiología , Liquen Plano/etiología , Enfermedades de las Glándulas Sudoríparas/complicaciones , Glándulas Sudoríparas/fisiología , Sudoración/fisiología , Adulto , Anciano , Fármacos Dermatológicos/uso terapéutico , Femenino , Calor , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
BACKGROUND: The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. OBJECTIVES: To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. METHODS: We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. RESULTS: AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. CONCLUSIONS: These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses.
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Autoanticuerpos/metabolismo , Erupciones por Medicamentos/inmunología , Plaquinas/inmunología , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Estudios de Casos y Controles , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Eosinofilia/inmunología , Femenino , Humanos , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Estudios RetrospectivosRESUMEN
BACKGROUND: Drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/TEN and beyond the acute stage of both diseases. METHODS: Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS (n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV) DNA loads sequentially determined by real-time polymerase chain reaction during a 2-year period after onset. RESULTS: Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV-6 loads were exclusively detected in DIHS/DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them. CONCLUSIONS: Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow-up period, which may contribute, at least in part, to the difference in the clinical manifestations and long-term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/DRESS.
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Erupciones por Medicamentos/complicaciones , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Herpesviridae/genética , Activación Viral , Adulto , Anciano , ADN Viral , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Herpesviridae/efectos de los fármacos , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Fenotipo , Estudios Retrospectivos , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/diagnóstico , Factores de Tiempo , Carga Viral , Activación Viral/efectos de los fármacosRESUMEN
When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
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Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/prevención & control , HumanosRESUMEN
BACKGROUND: Although infectious agents have long been implicated in the induction or exacerbation of pemphigus vulgaris (PV), a convincing role for the agent in the aetiology of PV has not been established. OBJECTIVES: To establish the association with PV and herpes simplex virus (HSV). PATIENTS AND METHODS: We examined saliva for the presence of HSV DNA after the onset of PV initially localized to the oral lesions in addition to conventional serological tests and immunohistochemistry. RESULTS: We successfully detected high levels of HSV DNA in the saliva samples from six of 16 patients with PV at the earliest stage, who had no episodes of herpes simplex. The prevalence (37·5%) of detecting HSV DNA in the patients with PV was lower than that of eczema herpeticum (56·5%), but comparable to that in patients with herpes labialis (30·0%). Copy numbers of the HSV DNA were rather higher than those with herpes labialis and with eczema herpeticum. In general, detection of HSV DNA in saliva was transient and restricted to the earliest phase of the disease. In addition, anti-HSV immunoglobulin (Ig) G titres in patients with PV were significantly higher than those in patients with virologically confirmed HSV-induced disorders. All salivary HSV DNA-positive patients with PV had run a more complex, intractable course refractory to conventional therapy. CONCLUSIONS: Detection of HSV DNA in saliva is a useful and noninvasive, quantitative method for establishing the role of HSV in the pathogenesis of PV and for identifying individuals at greater risk for subsequently developing refractory PV.
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Herpes Simple/complicaciones , Enfermedades de la Boca/virología , Pénfigo/virología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , ADN Viral/análisis , Femenino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/fisiología , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Saliva/virología , Activación Viral/fisiologíaAsunto(s)
Dolor Abdominal/virología , Gastroenteritis/virología , Herpes Zóster/fisiopatología , Vasculitis por IgA/virología , Inmunoglobulina A/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Herpesvirus Humano 3/fisiología , Humanos , Masculino , Persona de Mediana Edad , Sangre Oculta , Activación Viral/fisiología , Adulto JovenAsunto(s)
Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Enfermedad de Bowen/tratamiento farmacológico , Clobetasol/administración & dosificación , Glucocorticoides/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Anciano , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Esquema de Medicación , Quimioterapia Combinada , Estudios de Seguimiento , Factores de Transcripción Forkhead/metabolismo , Humanos , Imiquimod , Pomadas , Linfocitos T Reguladores/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Distinctions between 'linear lichen planus' (LP) and 'zosteriform LP' are difficult to determine solely based on clinical findings. OBJECTIVE: The aim of this study is to determine whether the presence of the varicella-zoster virus (VZV) antigens could be used to differentiate the zosteriform LP from the linear LP. METHODS: We immunohistochemically investigated the presence of in vivo localization of VZV antigens in 8 LP lesions (zosteriform LP: n = 5, linear LP: n = 3). RESULTS: We describe 2 cases of zosteriform LP without apparent prior episodes of herpes zoster, in whom VZV antigens were detected in the eccrine epithelium. Further analysis showed that VZV antigens were exclusively detected in the eccrine epithelium in the zosteriform LP lesions, but not in the linear LP lesions. CONCLUSION: Etiological differences exist between zosteriform LP and linear LP. The presence of VZV antigens in lesional skin of the former indicates a possible triggering role of this virus in the pathogenesis of this variant.
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Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/análisis , Herpes Zóster/diagnóstico , Herpesvirus Humano 3/inmunología , Liquen Plano/diagnóstico , Proteínas del Envoltorio Viral/análisis , Adulto , Anciano , Diagnóstico Diferencial , Glándulas Ecrinas/virología , Femenino , Herpes Zóster/inmunología , Herpes Zóster/virología , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Liquen Plano/inmunología , Liquen Plano/virología , Masculino , Piel/patologíaAsunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Eccema Dishidrótico/inducido químicamente , Eosinofilia/inducido químicamente , Adulto , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Eccema Dishidrótico/inmunología , Eosinofilia/inmunología , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Inmunoglobulina G/metabolismoRESUMEN
BACKGROUND: It is well known that varicella-zoster virus (VZV) exhibits tropism for the epidermis and follicular epithelium, while little attention has been paid to eccrine gland and duct involvement by VZV. The presence of herpetic syringitis in immunocompromised hosts suggested the possibility of eccrine gland and duct involvement by VZV. OBJECTIVES: To determine whether VZV antigens could be detected in eccrine gland or duct epithelium of herpes zoster (HZ) lesions obtained at various intervals after the onset of a rash, and whether this expression could also be detected in eccrine units from other inflammatory disease lesions suggestive of VZV infection. METHODS: We investigated immunohistochemically in vivo localization of VZV glycoprotein E (gE) antigen in HZ lesions and control inflammatory disease lesions, using the murine monoclonal antibody directed against the VZV gE. RESULTS: VZV gE was differentially detected in the epidermis, follicular and eccrine epithelium, and dermal infiltrating cells in HZ lesions obtained at various intervals after onset. The VZV gE was most persistently detected in eccrine units, regardless of the age of individual HZ lesions, compared with keratinocytes and follicular epithelium. the ge expression was also observed in other inflammatory disease lesions suggestive of vzv infection. CONCLUSIONS: Immunohistochemical detection of VZV gE in eccrine epithelium can be a subtle clue to the diagnosis of HZ which displays most unusual manifestations, and VZV-related disorders.
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Antígenos Virales/metabolismo , Glándulas Ecrinas/virología , Herpes Zóster/inmunología , Herpesvirus Humano 3/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
The function of murine dendritic epidermal cells (dEC) remains largely speculative, probably because of the lack of a suitable in vivo model, although previous studies suggest that gamma/delta+ dEC may have originally evolved to serve as a self-protection mechanism(s). Our previous study demonstrated that the epidermis of mice that had spontaneously recovered from cutaneous graft-vs-host disease (GVHD) induced by local injection of CD4+ autoreactive T cells contained unexpectedly large numbers of dEC and became resistant to subsequent attempts to induce GVHD in a site-restricted manner, suggesting that the resistance is mediated by dEC. However, because alpha/beta+ dEC as well as gamma/delta+ dEC were greatly increased in number in the epidermis, it was unclear whether gamma/delta+ dEC are indeed responsible for this protection. The availability of this murine model and mice selectively lacking gamma/delta T cells as a result of disruption of the T cell receptor C delta gene segment allowed us to investigate the role of gamma/delta+ dEC. In the epidermis of gamma/delta T cell-deficient mice (delta-/-), a congenital lack of gamma/delta+ dEC was substituted for by alpha/beta+ dEC of either a CD4-8+ or a CD4-8- phenotype. After intradermal injection of the autoreactive T cells, delta-/- mice developed significantly enhanced delayed-type hypersensitivity responses and cutaneous GVHD, which persisted longer than in heterozygous littermate controls (delta+/-). Surprisingly, resistance to the cutaneous GVHD was not induced in the epidermis of delta-/- mice after spontaneous recovery from the GVHD, whereas the "susceptible" epidermis of delta-/+ mice contained large numbers of alpha/beta dEC comparable to those in "resistant" epidermis of delta+/- mice. Injection of day 16 fetal thymocytes from wild-type mice into delta-/- mice resulted in the appearance of donor-type gamma/delta+ dEC in the epidermis, and reconstitution with gamma/delta+ dEC restored the protective immune response of the epidermis against the GVHD to nearly normal levels. These results indicate that gamma/delta+ dEC are responsible for the site-restricted protection against cutaneous GVHD.
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Células Dendríticas/inmunología , Enfermedad Injerto contra Huésped/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Trasplante de Piel/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Células Clonales , Modelos Animales de Enfermedad , Células Epidérmicas , Epidermis/inmunología , Hipersensibilidad Tardía , Inmunidad Innata , Inmunoterapia Adoptiva , Ratones , Ratones Endogámicos C57BL , Ratones MutantesRESUMEN
The cutaneous graft-versus-host disease (GVHD) lesions induced by intradermal injection of cloned autoreactive T cells have been shown to subside rapidly and the epidermis returns to normal 2 wk after injection. Those mice that had spontaneously recovered from the cutaneous GVHD became resistant to subsequent attempts to induce the cutaneous GVHD by the T cells while maintaining their activity to mount delayed-type hypersensitivity (DTH) responses and to induce the enlargement of the popliteal lymph nodes (PLN). The resistance appeared to be restricted to the epidermal structures of the injection sites, suggesting the involvement of locally acting suppression mechanisms. This local resistance was not specific for the clonotype used for the induction of the resistance. A loss of the epidermal integrity by an attack of T cells capable of producing cutaneous GVHD was a prerequisite for the induction of the resistance. By up to at least 8 mo after injection of the T cells, no mice became susceptible to the cutaneous GVHD again, provided that the T cells were injected into the same footpad sites that had initially received the T cells. This resistance correlated well with the great increase (20-30-fold) in Thy-1+ EC number. The great increase in the number of Thy-1+ EC following destruction of epidermal structures may be important in protecting the epidermal integrity from an additional attack by T cells.
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Antígenos de Superficie/inmunología , Enfermedad Injerto contra Huésped , Hipersensibilidad Tardía , Piel/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales , Antígenos de Superficie/análisis , Línea Celular , Células Clonales , Epidermis/inmunología , Femenino , Técnica del Anticuerpo Fluorescente , Inmunidad Celular , Ratones , Ratones Endogámicos C57BL , Linfocitos T/trasplante , Antígenos Thy-1RESUMEN
Nonpigmenting fixed drug eruption (NPFDE) is clinically indistinguishable from Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) in its initial presentation. The traditional paradigm that epidermal changes are absent in NPFDE cannot be easily reconciled with the clinical resemblance to SJS/TEN. We therefore investigated whether NPFDE is pathogenetically different from pigmented FDE (PFDE) or SJS/TEN and which factors are responsible for the lack of hyperpigmentation. NPFDE lesions before challenge were characterized by larger numbers of CD8+ intraepidermal T cells associated with a paucity of melanocytes, compared with those in PFDE. Very high levels of serum interleukin (IL)-10 were noted after clinical challenge. We conclude that NPFDE is a clinical syndrome with heterogeneous histological expression. NPFDE with epidermal involvement may be an abortive form of SJS/TEN, in which progression to TEN can be prevented by IL-10.
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Citocinas/sangre , Erupciones por Medicamentos/patología , Interleucina-10/sangre , Síndrome de Stevens-Johnson/patología , Anciano , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
BACKGROUND: Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS). AIM: To investigate immunological alterations and underlying viral infections that could contribute to the variability in the clinical presentations of these diseases. METHODS: We retrospectively analysed clinical variables, serum immunoglobulin levels, numbers of circulating white blood cells, lymphocytes and their subsets, serum levels of several cytokines, and underlying viral infections in both drug reactions, using samples obtained at onset from 9 patients with SJS/TEN and 19 patients with DIHS/DRESS. RESULTS: There were significant differences between the two drug eruptions in the duration of drug intake before onset, the levels of IgG, IgA and IgM, the numbers of circulating white blood cell, lymphocyte, CD3+ T cell and CD8+ T cells, the serum levels of interferon-γ, and the titres of anti-herpes simplex virus IgG at onset. CONCLUSIONS: The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions. Elucidating these host factors may provide a basis for therapeutic approaches in patients with severe drug reactions.
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Eosinofilia/inmunología , Síndrome de Stevens-Johnson/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/sangre , Virus ADN/aislamiento & purificación , Erupciones por Medicamentos/sangre , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/virología , Eosinofilia/sangre , Femenino , Humanos , Inmunoglobulinas/sangre , Recuento de Leucocitos/estadística & datos numéricos , Recuento de Linfocitos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Virus ARN/aislamiento & purificación , Estudios Retrospectivos , Síndrome de Stevens-Johnson/sangre , Síndrome de Stevens-Johnson/virologíaRESUMEN
OBJECTIVES: Cytomegalovirus (CMV) reactivation in patients with severe drug eruption on immunosuppressive therapy often leads to fulminant disease and even mortality, yet there are no biomarkers to accurately predict CMV reactivation either before or after immunosuppressive therapy. We aimed to assess whether patients who develop CMV reactivation (CMV-positive cases) have distinct immunological profiles from CMV-negative cases before and after immunosuppressive therapy. METHODS: We performed serial cytokine/chemokine and regulatory T cells (Tregs) assessments of 45 patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic syndrome (DRESS) during a follow-up period of nearly three years after onset. RESULTS: Elevated IL-8, IL-10, IL-12p40, IL-15, TNF-α, G-CSF, and MIP-1α levels at baseline were associated with later development of CMV reactivation, while after starting treatment, IL-10 and IL-15 levels were associated with the onset of CMV reactivation; the use of corticosteroids obscured the large differences in these cytokines at baseline. CMV-positive cases were found to have normal Tregs frequencies at baseline, while negative cases had elevated frequencies. Higher eotaxin, IL-10, and G-CSF levels and lower IL-12p40 levels at baseline might be used for predicting the development of lethal CMV disease. CONCLUSIONS: The algorithm based on these results showed an accurate association with CMV reactivation.