SEARCH

SEARCH BY CITATION

Keywords:

  • allergens;
  • asthma;
  • Churg–Strauss syndrome;
  • IgE;
  • vasculitis

Abstract

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Background:  The asthmatic-prodromal phase of Churg–Strauss syndrome (CSS) is usually considered allergic, but data about the involved allergens are scarce. The aim of our work was to examine the prevalence of allergy in a group of CSS patients and in two control groups of persistent asthmatic subjects selected for eosinophilia >10% [first control group patients (CGP1)] and eosinophils <6% [second control group patients (CGP2)].

Methods:  The respiratory symptoms, and the results of prick test and/or RAST for the common allergens, performed before the vasculitic phase in 51 CSS, were retrospectively evaluated and compared with those of 46 CGP1 and 50 CGP2.

Results:  31.4% of CSS vs 67.4% of CGP1 (P = 0.0004) and vs 58.0% CGP2 (P = 0.007) were allergic. The number of subjects with seasonal allergies was lower in CSS vs CGP1 (P = 0.0069) and vs CGP2 (P = 0.0002). The number of perennial allergies was significantly higher in CSS than in both control groups (CSS vs CGP1, P = 0.0108; CSS vs CGP2, P = 0.0079). The subjects allergic to Dermatophagoides were prevalent in CSS vs CGP1 (P = 0.0045) but not vs CGP2.

Conclusions:  The evidence of allergy, considered as the demonstration of specific IgE consistent with the clinical history, is present in less than one-third of CSS and the higher prevalence of seasonal allergies in the controls disagrees with persistent asthma. Allergy may be only one of several mechanisms triggering exacerbation of asthma or supporting chronic airway inflammation as in asthma in general. Alternatively, unidentified allergens may play a role.

Churg–Strauss syndrome (CSS) is a rare form of eosinophil-rich systemic necrotizing vasculitis affecting small to medium size vessels (1, 2). Three successive phases can be distinguished in the majority of patients: a prodromal, an eosinophilic-infiltrative and the vasculitic phase (3–6). In accordance with the American College of Rheumatology (ACR) 1990, asthma, eosinophilia >10%, mononeuropathy or polyneuropathy, pulmonary infiltrates nonfixed, paranasal sinuses abnormality and biopsy with extravascular eosinophils are the major classification criteria of the syndrome (7). Adult-onset asthma is considered as the central feature (8). At last CSS is considered to be one of the antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (9, 10), even though ANCAs are present in only 40% of CSS patients and their presence or absence is associated with two different clinical phenotypes (11, 12). The prodromal phase, characterized by asthma with upper respiratory symptoms as rhinitis, sinusitis and nasal polyposis, is generally thought to be allergic.

The role of common allergens is scarcely reported in the Churg–Strauss English literature: Chumbley et al. (13) described that allergic rhinitis occurred in 21 of 30 patients and Lanham et al. (3) pointed out that 12 of 16 patients had allergic rhinitis and skin prick tests were positive in 8 of 10 patients tested. They both, however, did not specify the identified allergens and their consistency with the respiratory symptoms. Afterwards, Hayakawa et al. (14) underlined that skin test and IgE radio-allergo-sorbent test (RAST) revealed that less than half of 11 subjects were atopic. The aim of our work was to examine the prevalence of respiratory allergy in a cohort of consecutive unselected CSS patients and in two different groups of asthmatic subjects.

Patients and methods

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

CSS patients

We identified 51 patients (19 males and 32 females) in whom CSS was diagnosed clinically in two general hospitals in northern Italy between 1985 and 2005 as described by Guillevin et al. (4), when asthma, hypereosinophilia (>10% or >1500 cells/mm3), and clinical manifestations consistent with systemic vasculitis, with or without histologic evidence, were present. Hypereosinophilia was not mandatory in the case of four patients previously treated with oral steroid for asthma in the presence of histologic confirmation (vasculitis plus extravascular eosinophils). CSS was defined according to the Chapel Hill Consensus Conference nomenclature (2).

First control group patients (CGP1)

We chose 46 (20 males and 26 females) ANCA-negative asthmatic patients with eosinophilia >10% and history of rhinitis with paranasal sinuses abnormalities, confirmed by computed tomography, in which CSS and the presence of the common parasites had been excluded.

Second control group patients (CGP2)

We chose 50 patients (13 males and 37 females) suffering from persistent asthma, with or without upper respiratory symptoms, with eosinophils <6% and lower than 600/mm3.

Methods

The medical records were examined retrospectively. Asthma had been diagnosed and classified in conformity with the revised 2002 Global Initiative for Asthma (GINA) (15). Prick test results were taken into account when performed according to the universally recognized recommendations (16).

Serum total and specific IgE were considered when determined by RAST (Pharmacia Diagnostic, Uppsala Sweden). In CSS patients, prick test and RAST were taken into account when performed before the onset of the vasculitic phase and before the prolonged treatment with high doses of oral/parental corticosteroids and/or immunosuppressants. The results of available skin prick tests and/or RAST were critically revaluated on the basis of the patient’s clinical history.

In conformity with the current guidelines (17, 18) for allergic rhinitis and asthma, the diagnosis of allergy was confirmed in the case of consistency between allergen exposition, recurrence of symptoms (seasonal and/or perennial) and the results of pricks test and/or RAST.

The inquired data in the medical records and the methods are explained in Table 1.

Table 1.   The inquired data in the medical records of the patients with Churg–Strauss syndrome (CSS), of the control patients and methods
  1. *In the case of CSS prick test and RAST performed before the vasculitic phase.

Sex
Rhinitis
Asthma
Asthma severity
Sinusitis
Nasal polyposis
Allergen professional exposition
Perennial recurrence of symptoms
Seasonal worsening of symptoms
Age at asthma onset
Age at diagnosis
Food allergy or intolerance
Drug allergy or intolerance
Contact dermatitis
Insect venom allergy
Treatment with inhaled corticosteroids
Treatment with oral or parental corticosteroids
Treatment with immunosuppressants
Prick test with commercial allergenic standardized extracts, inclusion of histamine 10 mg/ml positive control and negative diluent control*
Specific IgE determination by RAST (Pharmacia Diagnostic, Sweden) expressed in kU/l S.I. WHO 75/502: positive when > 0.35 kU/l*
Allergens tested by prick test and/or RAST: pollens from wind-pollinated flowering plants of our area (birch, grass, pellitory, plantain, mugwort and short-ragweed), molds (aspergillus, alternaria and cladosporium), dermatophagoides pteronyssinus and dermatophagoides farinae and pets dander (cat and dog), latex in case of professional exposition
Total IgE determination (Pharmacia Diagnostic, Sweden): elevated when > 100 kU/l
Eosinophils number/μl
Diagnosis of allergy confirmed only in the case of consistency between allergen exposition, recurrence of symptoms (seasonal and/or perennial) and the results of pricks test and/or RAST
The main clinical features of the CSS patients during the vasculitic phase
ANCA status of the CSS patients

Statistical analysis

The analyses were performed using ministat statistical software, release 1.1 (Pubblicazioni Medico Scientifiche, Udine, Italy); and only the Fisher’s exact test was performed using sas System software (SAS Institute Inc., Cary, NC, USA). The significance of difference between variables was assessed by the Wilcoxon test, for independent samples, for continuously distributed variables and the chi-square (χ2) test or Fisher’s exact test, when χ2 may not be a valid test, for categorical variables. P-values less than 0.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

In 42 of the 51 CSS, the allergic status had been evaluated at the Allergy, Clinical Immunology and Pneumology Outpatients Clinics of our hospitals before the onset of the vasculitic phase. Their medical histories and the results of the allergy tests were kept in the database of these facilities. The nine previously unknown patients were in possession of the results of prick test and/or RAST and clinical evaluation performed in other reliable allergy facilities. At the moment of the allergy evaluation, the patients were suffering only from upper and lower respiratory symptoms.

The details of the treatments with inhaled and/or oral glucocorticosteroids at the moment of allergy evaluation are reported in Table 2. No patient had been treated with immunosuppressants before the prick test and RAST.

Table 2.   Main clinical features and corticosteroid treatment of patients with Churg–Strauss syndrome and controls
 CSS (51)CGP1 (46)CGP 2‡ (50)P (CSS vs CGP1)P (CSS vs CGP2)P (CGP1 vs CGP2)
  1. Categorical variables are reported as number (percent), and continuous variables are reported as median (range).

  2. CSS, Churg–Strauss syndrome; CGP1, first control group patients; CGP2, second control group patients; M, male; F, female; NS, not significant; NE, not evaluated.

  3. *9 patients were not examined by computed tomography or Rx.

  4. †Number of patients with coexisting specific IgE and elevated total IgEs out of total of patients with elevated total IgEs.

  5. ‡Interquartile 25–75% range.

  6. §Or equivalents/daily.

Age at diagnosis (years)56.3 (46.0–66.4)‡50.7 (37.8–619)‡36.5 (28.4–49.2)NS<0.000010.0002
M/F19/3220/2613/37NSNSNS
Asthma51/51 (100)46/46 (100)50/50 (100)NSNSNS
Age at asthma onset (years)41.0 (25.2–54.3)‡38.5 (26.8–48.2)‡31.0 (24.4–44.2)NS0.0402NS
Rhinitis50/51 (98)46/46 (100)35/50 (70)NS0.00010.00006
Nasal polyposis14/51 (27.5)14/46 (30.4)1/50 (2)NS0.00030.0001
Sinusitis42/42 (100)*46/46 (100)3/50 (6)NS<0.00001<0.00001
Perennial recurrence symptoms51/51 (100)46/46 (100)50/50 (100)NSNSNS
Seasonal worsening symptoms6/51 (11.8)24/46 (52.2)26/50 (52)0.000020.00001NS
Eosinophil number (/μl) (range)2440 (1462–8181)‡1048 (865–1402)‡350 (201.3–442.5)<0.00001<0.00001<0.00001
Eosinophils >1500/μl37/47 (78.7)9/46 (19.6)0/50 (0)<0.00001NENE
Elevated total IgEs42/47 (89.4)30/34 (88.2)7/14 (50)NS0.00120.0042
Median total IgEs kU/l (range)318.5 (219–687)‡335 (168–583)‡116 (21.5–373.3)NS0.00440.0082
Specific IgE/elevated total IgEs†16/42 (38.1)24/30 (80)5/7 (71.4)0.0004NSNS
Drug allergy or intolerance6/51 (11.8)11/46 (23.9)11/50 (22)NSNSNS
Food allergy or intolerance6/51 (11.8)3/46 (6.5)4/50 (8)NSNSNS
History of contact dermatitis2/51 (3.9)6/46 (13)7/50 (14)NS0.0422NS
Insect venom allergy1/51 (2)0/461/50 (2)NENENE
Beclomethasone 500–1000 μg§32 (62.7)28 (60.9)46 (92)NS0.00050.0003
Beclomethasone >1000 μg§19 (37.3)18 (39.1)4 (8)NS0.00050.0003
Intermittent prednisone 25–50 mg§14 (27.5)11 (23.9)4 (8)NS0.01070.0319
Prednisone 5–10 mg§14 (27.5)11 (23.9)4 (8)NS0.01070.0319

The demographic and clinical features of the three groups and their statistical analysis are reported in Table 2. Eosinophils number was significantly higher in CSS patients vs both controls, and it was significantly higher in CGP1 vs CGP2 (Table 2). Thirty-seven of 47 CSS patients had blood eosinophils number higher than 1500/mm3vs 9 of 46 CGP1 (P < 0.00001).

Ten of 37 CSS (27%) tested by prick test resulted positive for a total of 19 allergens and 12 positive results were considered consistent with allergy. Fourteen (53.8%) of 26 CGP1 resulted positive by prick for a total of 31 allergens and 21 positive results were considered consistent with allergy. Twenty-five (54.3%) of 46 CGP2 resulted positive by prick for a total of 79 allergens and 54 positive results were considered consistent with allergy. So, 10 CSS vs 14 CGP1 (P = 0.031) and vs 25 CGP2 (P = 0.0122) resulted allergic, (CGP1 vs CGP2, P =0.9673) (Table 3).

Table 3.   Results of prick test performed in 37 patients with Churg–Strauss syndrome (CSS), in 26 first control (CGP1) and 46 second control (CGP2). (Only positivity consistent with clinical features is considered)
AllergenCSSCGP1CGP2
  1. *CGP1 vs CSS = 0.031.

  2. †CG2P vs CSS P = 0.0122.

  3. ‡CGP1 vs CGP2 = 0.9673.

  4. §Both positive dermatophagoides pteronyssinus and farinae.

  5. The results represent the number of allergic patients for a given allergen.

Dermatophagoides§512
Dermatophagoides§ + latex2-
Dermatophagoides§ + grass11
Dermatophagoides§ + short-ragweed12
Dermatophagoides§ + short-ragweed + grass2
Dermatophagoides§ + birch + grass1
Dermatophagoides§ + dog + short-ragweed  + grass1
Dermatophagoides§ + birch + grass  + short-ragweed1
Short-ragweed244
Short-ragweed + birch1
Short-ragweed + birch + cat1
Short-ragweed + dog1
Short-ragweed + cat1
Short-ragweed + cat + dog1
Short-ragweed + birch + grass + cat1
Grass + short-ragweed3
Grass + cat2
Grass13
Pellitory of the wall1
Cat1
Birch1
Pollens polyallergy (five pollens)1
Total number of patients (%)10 (27)*14 (53.8)‡25 (54.3)†

Nine of 35 CSS tested by RAST resulted positive for a total of 13 allergens, and all of them were consistent with allergy. Twenty-nine of 44 CGP1 resulted positive by RAST for a total of 64 allergens and 40 allergens were considered consistent with allergy. Twenty-three of 35 CGP2 resulted positive by RAST for a total of 82 allergens and 49 allergens were considered consistent with allergy. So, nine CSS patients (25.7%) vs 29 CGP1 (65.9%) (P = 0.0004) and vs 23 CGP2 (65.7%) controls (P = 0.0008) resulted allergic (CGP1 vs CGP2 P = 0.9855) (Table 4).

Table 4.   Results of RAST performed in 35 patients with Churg–Strauss syndrome (CSS), in 44 first control (CGP1) and 35 second control (CGP2). (Only positivity consistent with clinical features is considered)
AllergenCSSCGP1CGP2
  1. *CSS vs CGP1 = 0.0004.

  2. †CSS vs CGP2 = 0.0008.

  3. ‡CGP1 vs 2CGP = 0.9855.

  4. §CSS vs CGP1 = 0.1654.

  5. ¶CSS vs CGP2 = 0.6052.

  6. **CGP1 vs CGP2 = 0.6336.

  7. ††Both positive dermatophagoides pteronyssinus and farinae.

  8. The results represent the number of allergic patients for a given allergen.

Dermatophagoides††342
Dermatophagoides†† + cat1
Dermatophagoides†† + grass1
Dermatophagoides†† +short-ragweed111
Dermatophagoides†† + aspergillus  + short-ragweed1
Dermatophagoides†† + birch + grass1
Dermatophagoides†† + short-ragweed  + grass1
Dermatophagoides†† + birch + grass  + short-ragweed1
Dermatophagoides†† + dog + grass  + short-ragweed1
Dermatophagoides†† + cat  + short-ragweed1
Dermatophagoides†† + cat + dog1
Aspergillus1
Short-ragweed195
Short-ragweed + birch11
Short-ragweed + dog1
Short-ragweed + dog + cat1
Short-ragweed + birch + grass + cat1
Grass + short-ragweed13
Grass + cat2
Grass123
Dog + grass1
Dog1
Mugwort1
Birch + aspergillus1
Pellitory of the wall11
Pollens polyallergy (five pollens)1
Total number of patients (%)9 (25.7)*29 (65.9)‡23 (65.7)†
Number allergic patients in oral prednisone treatment5/14 (35.7%)§7/11 (63.6%)**2/4 (50%)¶

Five of 14 CSS (35.7%), seven of 11 CGP1 (63.6%) and two of four CGP2 (50%) who received treatment with prednisone and who were still treated with prednisone 5–10 mg daily at the moment of RAST resulted allergic without statistical difference among the three groups (Table 4).

Prick test and RAST were both performed in 21 CSS, 24 CGP1 and 31 CGP2. The two tests agreed (in terms of positive or negative) in 18 (85.7%) CSS, in 20 (83.3%) CGP1 and in 31 (100.0%) CGP2. RAST identified one more consistent allergen in one CSS patient and in one CGP2 patient, which resulted negative by prick test. Conflicting results (positive prick test and negative RAST or vice versa) were found in three CSS and four CGP1 patients: all of them were considered allergic because of the consistency of the positive results with the clinical history. Considering the results of the patients studied by both prick test and RAST, allergy was diagnosed in five of 21 CSS (23.8%) vs 16 of 24 CGP1 (66.7%), P = 0.004 and vs 19 of 31 CGP2 (61.3%), P = 0.007; CGP1 vs CGP2, P = 0.681.

Combining the results of prick test and/or RAST, 16/51 (31.4%) CSS, 31/46 (67.4%) CGP1 and 29/50 (58%) CGP2 patients were considered allergic: CGP1 vs CSS, P = 0.0004; CGP2 vs CSS, P = 0.007; CGP1 vs CGP2, P = 0.3424 (Table 5). The number of perennial allergies were prevalent in CSS patients compared with the two control groups, 15 out of 22 (68.2%) total allergies vs 15/43 (34.9%) in CGP1, P = 0.0108 and vs 22 out of 62 (35.5%) in CGP2, P = 0.0079; in particular, the number of patients with allergy to Dermatophagoides was significantly higher in CSS (11/16, 68.7%) vs CGP1 (8/31, 35.5%) (P = 0.0045) but not vs CGP2 patients (12/29, 41.4%) (P = 0.0787).

Table 5.   Combined results of prick test and/or RAST performed in 51 patients with Churg–Strauss syndrome (CSS), in 46 first control (CGP1) and 50 second control (CGP2). (Only positivity consistent with clinical features is considered)
AllergenCSSCGP1CGP2
  1. *CGP1 vs CSS P = 0.0004.

  2. †CGP2 vs CSS P = 0.007.

  3. ‡CGP1 vs CGP2 P = 0.3424.

  4. §both positive dermatophagoides pteronyssinus and farinae.

  5. The results represent the number of allergic patients for a given allergen.

Dermatophagoides§742
Dermatophagoides§ + latex2
Dermatophagoides§ + cat1
Dermatophagoides§ + grass21
Dermatophagoides§ + short-ragweed112
Dermatophagoides§ + aspergillus  + short-ragweed1
Dermatophagoides§ + grass  + short-ragweed2
Dermatophagoides§ + birch + grass1
Dermatophagoides§ + birch + grass  + short-ragweed1
Dermatophagoides§ + dog + grass  + short-ragweed1
Dermatophagoides§ + cat + short-ragweed1
Dermatophagoides§ + cat + dog1
Aspergillus1
Cat1
Short-ragweed195
Short-ragweed + birch1
Short-ragweed + birch + cat1
Short-ragweed + dog1
Short-ragweed + cat11
Short-ragweed + cat + dog1
Short-ragweed + birch + grass + cat1
Grass + short-ragweed13
Grass + cat2
Grass124
Dog + grass1
Dog1
Mugwort1
Birch1
Birch + aspergillus1
Pellitory of the wall11
Pollens polyallergy (five pollens)1
Total number of patients (%)16 (31.4%)*31 (67.4%)‡29 (58%)†

By reverse, the number of patients with seasonal pollen allergies was significantly lower in CSS vs both control groups, 6/16 CSS (37.5%) vs 24/31 CGP1 (77.4%), P = 0.0069 and vs 26/29 CGP2 (89.6%), P = 0.0002, whereas there was not difference between the two control groups (P = 0.2038).

Allergy to short ragweed was diagnosed in 4/16 (25%) of CSS patients, in 14/31 CGP1 (45.2%) and in 18/29 CGP2 (62.1%) showing a significant difference in CGP2 vs CSS (P = 0.0173). Total IgEs had been determined in 47 CSS patients, in 34 CGP1 and in 14 CGP2 controls: the results and their association with specific IgEs are reported in Table 2.

Antineutrophil cytoplasmic antibodies were positive in 14 of 42 CSS (33.3%): 12 p, 1 p-c, 1 c; three out of 14 ANCA-positive and eight out of 28 ANCA-negative subjects resulted allergic (P = 0.6196). The main clinical features of CSS during the vasculitic phase and their correlation with allergy and ANCA status are reported in Table 6. Allergic patients had a higher frequency of heart involvement (31.2%vs 5.7%, P = 0.0139). Further statistical analysis on subgroups of patients divided on the basis of allergy, and ANCA status was not performed because of the small numbers of patients in each subgroup.

Table 6.   Main clinical features of patients with Churg–Strauss syndrome and their correlation with allergy and ANCA status
Main clinical featuresAllergic (16)‘Non’allergic (35)Total (51)Allergic (11)‘Non’allergic (31)Total (42)
ANCA+ (3)ANCA− (8)ANCA+ (11)ANCA− (20)
  1. *= 0.0139 (heart involvement in Allergic vs‘Non’allergic patients).

  2. Due to the small numbers in each subgroups of ANCA tested patients, the statistical analysis was performed only comparing Allergic vs‘Non’allergic patients.

  3. Categorical variables are reported as number (percent).

  4. CSS, Churg-Strauss syndrome; ANCA, antineutrophil cytoplasmic antibodies; ANCA+, ANCA positive patients; ANCA−, ANCA negative patients; CNS, central nervous system.

Constitutional symptoms62.574.370.633.362.581.870.069.0
Skin involvement62.554.356.966.650.072.740.052.4
Lung involvement37.557.151.033.337.545.460.050.0
Heart involvement31.2*5.713.733.337.505.011.9
Gastrointestinal involvement31.214.319.633.337.518.215.021.4
Peripheral neuropathy56.271.466.733.362.572.780.071.4
CNS involvement6.217.113.733.309.125.016.7
Renal involvement12.534.327.5025.072.715.030.9

Discussion

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

This is the first study that, even if retrospectively, investigates the prevalence of atopy in a large cohort of CSS patients by means of the current guidelines. We found that evidence of allergy, considered as the demonstration of specific IgEs consistent with the clinical history of the patient, is present in less than one-third of CSS patients in comparison with more than 65% of a control group constituted of patients with asthma, very similar upper respiratory involvement, and eosinophilia (>10%) and in comparison with 58% of a second group of less severe asthmatic subjects with eosinophils <6%, whereas the prevalence of allergic subjects between the two control groups is not statistically different.

The prodromal phase of CSS is characterized by typical symptoms as rhinitis, sinusitis, frequently nasal polyposis and adult asthma onset that is considered a central feature. The role of allergy in this phase is taken for granted by the English literature even though only few small series of patients have been described. Our result does not seem to support such well-established opinion.

Atopy is considered as an important factor that predisposes to the development of asthma, although its role is under discussion. An association between the prevalence of atopy and asthma has been suggested and so between the levels of IgE and asthma, but an association between the increase of atopy and the increase of asthma had been not proven (19, 20). The available epidemiological evidence suggest that the proportion of asthma cases attributable to atopy is less than one-half (21), but the proportion of people with asthma who are skin prick test positive varies considerably between different studies (15).

In addition to the common allergens, other perennial allergens are implicated in asthma: domestic mites such as Euroglyphus mainei, Tyrophagus, Glyciphagus and others, cockroach and fungi such as Candida and Penicillum (15) and even bacterial allergens as Chlamydia pneumoniae (22), whereas Candida is as an important allergen in nasal polyposis and it occurs in older age (23). Pollens are implicated in asthma exacerbations, but there is not evidence that allergy to pollens increases the risk of asthma (24). Moreover, the pollen maps may change accidentally or intentionally as a result of human actions.

Asthma can have an adult onset perhaps from the development of atopy later in the life, and viral infections may trigger asthma exacerbations (15). Moreover, a higher incidence of asthma in postmenopausal women taking estrogens had been suggested (25).

In this study, CSS and CGP1 patients are homogeneous for adult asthma onset and the age of CSS appearance is similar to the age of the CGP1 at diagnosis, whereas in CGP2 the age at diagnosis is significantly lower vs CSS and CGP1 and asthma onset age is lower vs CSS but not vs CGP1. The persistence of asthma is exactly alike in the three groups, whereas the seasonal worsening is higher in CGP1 and CGP2 and upper respiratory involvement is statistically lower in CGP2.

The results of prick tests show that respiratory allergies are present in 27% of 37 CSS, 53.8% of 26 CGP1 and 54.3% CGP2 (CGP1 vs CSS, P = 0.031; CGP2 vs CSS, P = 0.0122), whereas the results of RAST show that atopy is present in 25.7% of 35 CSS patients vs 65.9% of 44 CGP1 (P = 0.0004) and vs 65.7% of 35 CGP2 (P = 0.0007) and, in the subjects treated with oral corticosteroids, RAST shows a nonsignificant lower number of allergic patients in CSS vs both controls.

Both prick tests and RAST were performed in 21 CSS patients, in 24 CGP1 and in 31 CGP2 controls; few conflicting results were interpreted on the basis of the clinical history: 5 of 21 CSS patients (23.8%) resulted allergic vs 16 of 24 CGP1 (66.6%) (P = 0.004) and vs 19 of 31 CGP2 (61.3%) (P = 0.007).

All the patients were studied at least by one test, prick test or RAST; combining the results, this study shows that respiratory allergies are present in less than one-third of CSS patients, in ∼67% of CGP1 patients (P = 0.0004) and in 58% of CGP2 (P = 0.007). The study shows moreover a prevalence of the number of perennial allergies in CSS vs CGP1 (P = 0.0108) and vs CGP2 (P = 0.0079) with a prevalence of patients allergic to house dust mites in CSS vs CGP1 (P = 0.0045); and a prevalence of patients with seasonal allergies in CGP1 (P = 0.0069) and CGP2 (P = 0.0002), whereas 45% of seasonal worsening in CGP1, 62.1% in CGP2 and 25% in CSS (CGP2 vs CSS, P = 0.0173) is caused by allergy to short ragweed.

When allergic patients were compared with ‘non’ allergic ones, a higher prevalence of heart involvement was found in the former. However, this clinical association, whose significance (if any), is unknown, deserves confirmation in a largest cohort of patients.

Essentially, the results of this study point out, even if in a different way, the poor significance of the common allergens in three groups of asthmatic patients: the controls show a high prevalence of allergy but lack of correlation between their perennial symptoms and the perennial allergens, whereas the CSS patients show a good correlation between their perennial symptoms and the perennial allergens but a low prevalence of allergy.

In our study, the proportion of CSS and CGP1 patients with elevated total IgEs is nearly 90%vs 50% of CGP2, but only 38% of CSS patients with elevated total IgEs show specific IgEs vs 80% of CGP1 (P = 0.0004). The proportion of asthma cases attributable to atopy, considering together the three groups, is 51.7%, percentage not far from the general asthma epidemiological evidence, whereas it is very different separately suggesting that mechanisms different from atopy are involved or may coexist in very similar clinical pictures.

In CSS, Dermatophagoides are the first cause of allergy, which is consistent with their perennial symptoms and with the evidence that the domestic mites are common indoor allergens associated with asthma (26–28). The above-mentioned less common allergens had not been tested in our patients and that could partly explain the poor prevalence of allergy in CSS and the low prevalence of perennial allergens in CGP1 and CGP2 in spite of the perennial recurrence of symptoms.

Allergy to short ragweed explains a large proportion of seasonal worsening in CGP1 and CGP2 but a smaller proportion in CSS patients: up to the beginning of the 1980s, the spread of short ragweed in our area was anecdotal but in the following decade, as in other European areas, short ragweed has reached a great spread becoming a relevant cause of pollinosis (29, 30). That allowed the development of atopy later in the life, even in the elderly, in people that had not met the short ragweed pollen previously and so may explain the late onset of upper and lower respiratory symptoms in a number of patients of our study and, perhaps, make less homogeneous CGP1 and CSS with regard to the onset age of asthma but also make us advised that atopy may have a late onset in the life because of changes in the environment.

This study demonstrates, even with the limitations given by the retrospective investigations and by the use of two different not entirely interchangeable (31) methods for demonstrating IgE antibodies, that the common allergens have a poor significance in the history of asthma in a series of 51 CSS patients and, perhaps, even in the two control groups in which the higher prevalence of atopy is barely correlated with the persistence of asthma. Finally, an eosinophil number higher than 1500/mm3 seems to be better suited to distinguish between CSS patients and CGP1 than eosinophil percentage >10.

The lack of associations with proven allergies recalls in CSS the suggestion, as in intrinsic asthma, of a form of autoallergy or an allergy to an undetected allergen (15, 32).

In short, we think that in the prodromal phase of CSS the role of allergy, considered as the demonstration of specific IgE consistent with the clinical history of the patients, may have been overemphasized as in asthma in general and that allergy may be only one of several mechanisms triggering exacerbation of asthma or supporting chronic airways inflammation. Alternatively, unidentified allergens might play a role at least in some patients.

Finally, in our opinion, a prospective study of specific IgEs, including the less common perennial allergens, in a sufficient large number of CSS patients is advisable.

References

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References
  • 1
    Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa. Am J Pathol 1951;27:277 301.
  • 2
    Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL et al. Nomenclature of systemic vasculitides: proposal of an international consensus conference. Arthritis Rheum 1994;37:187192.
  • 3
    Lanham JC, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg–Strauss syndrome. Medicine (Baltimore) 1984;63:6581.
  • 4
    Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg–Strauss syndrome: clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999;78:2637.
  • 5
    Eustace JA, Nadasdy T, Choi M. The Churg–Strauss syndrome. J Am Soc Nephrol 1990;10:10281055.
  • 6
    Noth I, Strek ME, Leff AR. Churg–Strauss syndrome. Lancet 2003;361:587594.
  • 7
    Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Churg–Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:10941100.
  • 8
    Guillevin L, Pagnoux C, Mouthon L. Churg–Strauss syndrome. Semin Respir Crit Care Med. 2004;25:535545.
  • 9
    Jennet JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337:15121523.
  • 10
    Savage CO, Harper R, Adu D. Primary systemic vasculitis. Lancet 1997;349:553558.
  • 11
    Sinico RA, Di Toma L, Maggiore U, Bottero P, Radice A, Tosoni C et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg–Strauss Syndrome. Arthritis Rheum 2005;52:29262936.
  • 12
    Sable-Fourtassou R, Cohen P, Mahr A, Pagnoux C, Mouthon L, Jayne D et al. Antineutrophil cytoplasmic antibodies and the Churg–Strauss syndrome. Ann Intern Med 2005;143:632638.
  • 13
    Chumbley LC, Harrison EG, De Remee RA. Allergic granulomatosis and angiitis (Churg–Strauss syndrome). Mayo Clin Proc 1977;52:477484.
  • 14
    Hayakawa H, Sato A, Yagy T, Shimizu T, Miyajima H, Taniguchi M et al. Clinical features and prognosis of Churg–Strauss syndrome. Nihon Kyobu Shikkan Gakkai Zasshi. 1993;31:5964.
  • 15
    Global Strategy for Asthma Management and Prevention. Revised 2002. NIH Publication No 02-3659. National institutes of Health, National Heart, Lung, and Blood Institute.
  • 16
    Good allergy practice. Standards of care for providers and purchasers of allergy services within the National Health Service. Royal College of Physicians and Royal College of Pathologists. Clin Exp Allergy 1995;25:586595.
  • 17
    Lemanske RF Jr. A review of the current guidelines for allergic rhinitis and asthma. J Allergy Clin Immunol 1998;101:S392S396.
  • 18
    Van Cauwemberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy 2000;55:116134.
  • 19
    Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl Med 1989;320:271277.
  • 20
    Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991;325:10671071.
  • 21
    Pearce N, Pekkanene J, Beasley R. How much asthma is really attributable to atopy? Thorax 1999;54:268272.
  • 22
    Emre U, Sokolovskaya N, Roblin PM, Schachter J, Hammerschlag MR. Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease. J Infect Dis 1995;172:265267.
  • 23
    Asero R, Bottazzi G. Clinical features of patients showing Candida hypersensitivity: an observational study. J Investig Allergol Clin Immunol 2004;14:309311.
  • 24
    Sears MR, Herbison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. The relative risk of sensitivity to grass pollen, house dust mite and cat dander in the development of childhood asthma. Clin Exp Allergy 1989;19:419424.
  • 25
    Asthma in women after menopause. Hormone replacement therapy may explain why many women over 50 develop this disease. Health News 2005;11:45.
  • 26
    Platts-Mills TA. Role of allergens in asthma and airway hyperresponsiveness: relevance to immunotherapy and allergen avoidance. In: KalinerMA, PersonCG, editors. Asthma: Its Pathology and Treatment. New York: Marcel Dekker, 1991, Chapter 22.
  • 27
    Nelson HS. The importance of allergens in the development of asthma and the persistence of symptoms. J Allergy Clin Immunol 2000;105:S628S632.
  • 28
    Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcoch AJ. Importance of dust mite and alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy 1993;23:812820.
  • 29
    Déchamp C, Méon H. Ambroisies, Polluants Biologiques. Lyon: Arpam-édition, 2002, 68.
  • 30
    Wopfner N, Gadermaier G, Egger M, Asero R, Ebner C, Jahan-Schmid B. The spectrum of allergens in ragweed and mugwort pollen. Int Arch Allergy Immunol 2005;138:337346.
  • 31
    Yunginger JW, Ahlstedt S, Egglestone PA, Homburger HA, Nelson HS, Ownby DR et al. Quantitative IgE antibody assays in allergic diseases. J Allergy Clin Immunol 2000;105:10771084.
  • 32
    Umibe T, Kita Y, Nakao A, Nakajima H, Fukuda T, Yoshida S et al. Clonal expansion of T cells infiltrating in the airways of no-atopic asthmatic. Clin Exp Immunol 2000;119:390397.