Clinical and biological hallmarks of acute Eczema herpeticum
We first analyzed clinical and laboratory data of patients in acute EH (Gr.1) and during follow-up phase (Gr.1fu) and compared the data to patients with history of EH (Gr.2). More males (71%) than females (29%) presented with acute episodes of EH (). This was not due to more frequent HSV infections since females had significantly more HSV episodes per year than males (females: 8.00±2.8 versus males: 1.6±0.7; p< 0.001).
Demographic characteristics; SD=standard deviation.
Only 1 out of 21 patients with acute EH reported use of a topical steroid to control their disease. None of the patients used topical calcineurin inhibitors. As shown by the SCORAD (and EASI, data not shown) evaluations, patients with acute EH had a higher clinical severity score than patients with history of EH (). However, this seemed to be mainly due to a greater severity for the head area involved by EH. There was a clear decrease of the clinical severity (SCORAD from 50.6±11.35 to 22.8±5.05; −55%, p<0.001) during the 6 week follow-up phase compared to the ADEH+HSV+ acute patients reaching a scoring which was significantly lower than for patients with history of EH (Gr.2: SCORAD: 41.87±10.17; p<0.001) (). There was no difference in the degree of improvement between patients with (n=6) and without (n=5) anti-inflammatory treatment in the follow-up phase (− 55% versus − 60% respectively; n.s.).
Figure 1 Comparison of the SCORAD between Eczema herpeticum patients during the acute phase of the disease and during remission of EH, 4–12 weeks after the acute episode. Additionally the mean ± SD of the SCORAD of the ADEH+HSV+ history group is (more ...)
There were no significant differences in the total leucocytes, neutrophils and eosinophils counts during the acute EH episode when compared to patients with history of EH (). In contrast, a lower level of lymphocytes was observed. This was due to significantly lower numbers of CD3+/CD4+ T-cells while CD19+ B-cells did not vary. Of note, monocytes were significantly higher in patients during acute EH than for patients with history of EH. During the follow up phase, all the above mentioned laboratory findings reached values which did not significantly differ from patients with history of EH.
Table 2 Comparison of the differential blood counts and the FACS-analysis between the several groups (ADEH+HSV+ during the acute phase and during remission (fu=follow-up examination; 4 –12 weeks after the acute episode), ADEH+HSV+ history; ADEH− (more ...)
Severe atopic dermatitis combined with allergic airway diseases (dermo-respiratory syndrome) correlates with the development of EH
We next evaluated whether patients with EH (acute and history; Gr.1+Gr.2/ADEH+HSV+) exhibit distinct clinical features when compared to AD patients without EH (Gr.3/ADEH−HSV+). The presence of EH episodes could not be explained by a tendency to have more HSV episodes since there was no significant difference in the frequency of recurrent HSV infections per year between patients with EH (ADEH+HSV+ acute and history) (mean 2.4 episodes/year) and AD patients with recurrent HSV infections without any episode of EH (ADEH-HSV+) (mean 2.6 episodes/year) nor between patients with AD (ADEH+HSV+ history and ADEH-HSV+) and patients without AD (NA HSV+) suggesting that AD is not associated with an increase in the number of HSV episodes.
There were significantly more males with EH (ADEH+HSV+ history: 77%) than females, and fewer males in the EH− group (ADEH-HSV+: 43%, p<0.001) (). However, males and females did not differ in terms of severity within groups. The mean age of onset of AD in patients with EH was (non-significantly) lower as compared to the other AD groups (4.89±8.15 vs 7.57±11.70 years).
Higher clinical scores were observed in patients with EH compared to patients of the other groups as appreciated by Rajka-Langeland, SCORAD and EASI scoring systems (). Based on Rajka-Langeland scores, the extent of the skin lesions (2.0 versus 1.5), itch intensity (2.1 versus 1.6) and the prevalence of eczematous skin lesions in the head and neck area (2.6 versus 1.4) was more pronounced in the ADEH+HSV+ group (Gr.1+Gr.2) when compared to Gr.3/ADEH−HSV+ patients (all p<0.001). Interestingly, the Rajka-Langeland score which, in contrast to SCORAD and EASI, more reflects the recent past history of AD in patients, suggested that patients with EH had overall a higher degree of severity in the past 3 months than patients without EH in their history. Similarly, as reflected by the Diepgen score, patients with history of EH exhibit a stronger atopic background than those without history of EH (23.35±6.17 vs 18.93±5.36; p<0.001). shows that distinct clinical items of the Diepgen score were significantly more prevalent in EH patients.
Figure 2 Mean values of several scores (SCORAD, Diepgen, EASI and Rajka-Langeland-Score) are shown for the ADEH+HSV+ acute, ADEH+HSV+ history and the two other AD+ groups (ADEH−HSV+ and ADEH−HSV−); SD=standard deviation. *p<0.05 (more ...)
Figure 3 Comparison of several clinical items of the Diepgen score between the ADEH+HSV+ history and the ADEH−HSV+ groups. *p<0.05 = statistically significant [Statistical analysis: comparisons of presence or absence of symptom between groups made (more ...)
Most importantly, patients with EH had significantly higher frequency of concomitant physician diagnosed asthma (64% versus 27%; p<0.001) and allergic rhinitis (86% versus 58%; p<0.001) than ADEH−HSV+ patients. Of note, patients with history of EH more often had siblings suffering from atopic dermatitis (36% versus 26%; p<0.001) and allergic rhinitis (46% versus 19%; p<0.001). We did not detect any significant difference with regard to all above mentioned clinical parameters when comparing ADEH−HSV+ patients to ADEH−HSV− patients (data not shown).
Biological phenotype of patients with history of Eczema herpeticum
The total serum IgE level of patients with history of EH (Gr.1+Gr.2/ ADEH+
) was significantly higher than in patients from Gr.3/ADEH−
(). Among the panel of allergens tested herein, specific IgE against Pityrosporum ovale (P. ovale) was significantly higher in AD patients with one or more episodes of EH than in the Gr.3/ADEH−
patients among those with positive tests (p=0.019) () (for more details about the values of the other tested allergens see supplemental material
Comparison of the total serum IgE level and the specific IgE (Pityrosporum ovale) between the ADEH+HSV+ (acute & history) and the two other AD+ groups (ADEH−HSV+ and ADEH−HSV−).
We did not find significant differences in total leucocytes, lymphocytes counts and sub-populations between patients with history of EH (Gr.2/ADEH+HSV+history) and patients without EH (Gr.3/ADEH−HSV+ and Gr. 4/ ADEH−HSV−). However, as expected there was a significant eosinophilia in all groups of patients with AD when compared to the control individuals of Gr.5/NA HSV+ and Gr.6/NA HSV−. However, there were no significant changes in any laboratory findings between the 2 control groups, i.e. Gr.5/NA HSV+ and Gr.6/NA HSV− ().