[A LONG PROSPECTIVE OBSERVATIONAL STUDY ON PREVALENCE OF ATOPIC DERMATITIS IN EARLY CHILDHOOD TO ADOLESCENCE].

BACKGROUND: There are few prospective observational studies on the prevalence of atopic dermatitis (AD) in children. We aimed to prospectively investigate the dynamics of change in the prevalence of AD from early childhood to adolescence. METHODS: We conducted a survey with a modified questionnaire to diagnose AD based on The International Study of Asthma and Allergies in Childhood questionnaire with 1230 13-year-old children who were born in the Minami ward, Yokohama City between May 2004 and June 2005 and had undergone physical examinations by dermatologists at 3 years of age. Among the 422 children who answered the questionnaire, 210 had undergone periodic physical examinations by dermatologists from 4 months to 3 years of age (Cohort 1), whereas 212 had undergone physical examinations only at 3 years of age (Cohort 2). RESULTS: The prevalence of AD was 16.9% in 422 children at 13 years of age, with 22.9%, 16.6%, 20.0% and 18.3% prevalence at 4 months, 18 months, 3 years and 13 years of age, respectively, in children who were followed up long-term. The frequency of AD occurrence per year decreased after the age of 3 years; a history of AD at this age was significantly related to AD at 13 years of age (Fisher's exact test, p<0.001). CONCLUSION: In conclusion, it was suggested that AD in 3-year-old children is one of the risk factors for the development of AD in 13-year-old children.

Japanese guidelines for occupational allergic diseases 2017.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients--Treatment and outcome.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. METHODS: To present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000-2013. RESULTS: Fifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000-2006 and 2007-2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN. CONCLUSIONS: Treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN.

Effects of oral administration of Lactobacillus acidophilus L-92 on the symptoms and serum cytokines of atopic dermatitis in Japanese adults: a double-blind, randomized, clinical trial.

OBJECTIVES: Several studies on lactobacilli have demonstrated they are effective against atopic dermatitis (AD) in children, but there are very few reports of their effects in adults. We investigated the changes in AD symptoms in adults after the ingestion of the Lactobacillus acidophilus strain L-92 (L-92), which has been shown to have a curative effect on AD in children. METHODS: A double-blind, parallel-group, placebo-controlled comparison was performed on 49 AD patients aged ≥16 years using heat-killed L-92. Skin lesions were assessed using the SCORing AD (SCORAD) index before the start of L-92 ingestion and 4 and 8 weeks after ingestion. Serum cytokine and blood marker levels were measured 8 weeks after the start of L-92 ingestion. RESULTS: The group that ingested L-92 had lower SCORAD scores than the controls (p = 0.002). The L-92 group also had decreased ratios of change for eosinophil count (p = 0.03) and increased ratios of change for serum TGF-ß (p = 0.03). Ratios of change for serum TGF-ß rose significantly (p = 0.04) in patients showing mitigated symptoms with L-92 administration. CONCLUSIONS: Administration of heat-killed L-92 was effective for AD symptoms in adults. L-92 may contribute to the suppression of Th2-dominant inflammation. Our preliminary trial is the first to report the effects of L-92 on adult AD.

Japanese Guideline for Occupational Allergic Diseases 2014.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Japanese Guideline for Occupational Allergic Diseases 2014.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A National Survey in Japan.

PURPOSE: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey. DESIGN: Retrospective, national trend survey . METHODS: Dermatological case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmological CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey. RESULTS: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < 0.001) and specific year in the survey (P < 0.001). CONCLUSIONS: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment.

Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population.

An anticonvulsant, carbamazepine (CBZ), is known to show incidences of cutaneous adverse drug reactions (cADRs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS). To identify a gene(s) susceptible to CBZ-induced cADRs, we conducted a genome-wide association study (GWAS) in 53 subjects with the CBZ-induced cADRs, including SJS, TEN and DIHS, and 882 subjects of a general population in Japan. Among the single nucleotide polymorphisms (SNPs) analyzed in the GWAS, 12 SNPs showed significant association with CBZ-induced cADRs, and rs1633021 showed the smallest P-value for association with CBZ-induced cADRs (P = 1.18 × 10⁻¹³). These SNPs were located within a 430 kb linkage disequilibrium block on chromosome 6p21.33, including the HLA-A locus. Thus, we genotyped the individual HLA-A alleles in 61 cases and 376 patients who showed no cADRs by administration of CBZ (CBZ-tolerant controls) and found that HLA-A*3101 was present in 60.7% (37/61) of the patients with CBZ-induced cADRs, but in only 12.5% (47/376) of the CBZ-tolerant controls (odds ratio = 10.8, 95% confidence interval 5.9-19.6, P = 3.64 × 10⁻¹5), implying that this allele has the 60.7% sensitivity and 87.5% specificity when we apply HLA-A*3101 as a risk predictor for CBZ-induced cADRs. Although DIHS is clinically distinguished from SJS and TEN, our data presented here have indicated that they share a common genetic factor as well as a common pathophysiological mechanism. Our findings should provide useful information for making a decision of individualized medication of anticonvulsants.

Decreased expression of semaphorin-3A, a neurite-collapsing factor, is associated with itch in psoriatic skin.

Pruritus is a common symptom of psoriasis, which affects quality of life. This symptom accompanies the hyper-innervation of sensory C-fibres in psoriatic lesions. Two extracellular molecules, nerve growth factor (NGF) and semaphorin-3A, regulate C-fibre extension. In this study, the expression levels of these 2 molecules in biopsy specimens from psoriatic and healthy skin were quantified by immunohistochemistry and quantitative reverse-transcription PCR. Semaphorin-3A expression was lower in the psoriatic samples compared with the healthy samples, whereas NGF was higher. C-fibre innervation in the epidermis was also increased in psoriatic skin. Semaphorin-3A mRNA expression was negatively correlated with itch intensity and severity of psoriasis. We propose that decreased semaphorin-3A and increased NGF expression levels may trigger the outgrowth of C-fibres, leading to pruritus.

Phenotypes of atopic dermatitis up to 36 months of age by latent class analysis and associated factors in Japan.

BACKGROUND: Atopic dermatitis (AD) in early childhood is the first allergic manifestation in the atopic march. Recently, latent class analysis (LCA) has revealed the presence of AD subgroups in childhood. OBJECTIVE: This study aimed to elucidate different AD phenotypes up to 36 months of age and identify factors associated with a particular AD phenotype in early childhood. METHODS: Pediatric allergists or dermatologists examined children who visited local public health centers in Chiba or Yokohama city at 4, 18, and 36 months of age for regular health checkups between 2003 and 2005. LCA was used to identify AD subtypes on the basis of the course of skin symptoms and comorbidity of other allergic diseases. After LCA, the association between genetic and environmental factors and AD phenotypes was assessed. RESULTS: A total of 1,378 children who underwent the 3 checkups were included. Complete data were available for 515 children up to 36 months of age. Of 515 children, 183 were diagnosed with AD at least at one out of the 3 time points. The LCA model of these children with AD separated 4 AD phenotypes: early-persistent (EP), early-transient (ET), late-onset (LO), and variable (V). Antibiotic use by 4 months of age was significantly higher in EP group than in other 3 groups. Mother's allergy was significantly higher in EP and LO groups than in other 2 groups. Passive smoking at 18 months of age was higher in LO group than in other groups. Furthermore, >80% of V group was born in spring-summer. CONCLUSION: We identified 4 AD phenotypes using LCA on the basis of the onset/course of AD and comorbidity of other allergic diseases and also identified several factors related to the particular phenotypes, which may be useful markers for the prediction of prognosis of AD in early childhood.

Intranasal administration of semaphorin-3A alleviates sneezing and nasal rubbing in a murine model of allergic rhinitis.

Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment.

Production of both IL-27 and IFN-gamma after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model.

Using an allergen-induced airway inflammation model, we show that an injection of alpha-galactosylceramide (alpha-GalCer), a ligand for invariant NK T (iNKT) cells, induced IL-27 and that this process is essential for the attenuation of the Th2 response. After the systemic administration of alpha-GalCer into the mice primed with OVA in alum, Th2 cytokine production of OVA-primed CD4(+) T cells in their lymph nodes, IgG1 and IgE Ab formation, and infiltration of eosinophils in bronchoalveolar lavage after the OVA challenge were suppressed. Systemic administration of rIFN-gamma into OVA-primed mice could not reproduce these effects of alpha-GalCer. IL-27p28 was detected both in the culture supernatant of alpha-GalCer-stimulated spleen cells and in the serum of the alpha-GalCer-treated mice, but not in the iNKT cell-deficient mice. Splenic iNKT cells produced IL-27p28 in the culture supernatant upon stimulation with PMA plus ionomycin, although the transcript of IL-27p28 in the iNKT cells was constitutively expressed regardless of the stimulation. By contrast, the transcript of IL-27EBI3 was induced in the iNKT cells upon stimulation with PMA plus ionomycin in vitro and with alpha-GalCer treatment in vivo, suggesting that IL-27 (p28/EBI3) could be produced by iNKT cells in an activation-dependent manner. Although repeated injections of rIL-27 did not substitute for the effects of a single injection of alpha-GalCer, administration of rIL-27 along with rIFN-gamma reproduced in vivo effects of the alpha-GalCer injection. These data indicate that production of both IL-27 and IFN-gamma by the alpha-GalCer treatment is responsible for suppression of the Th2 response and allergic inflammation.

Late-onset anaphylaxis due to poly (γ-glutamic acid) in the soup of commercial cold Chinese noodles in a patient with allergy to fermented soybeans (natto).

BACKGROUND: Fermented soybeans (natto) have been reported to induce IgE-mediated, late-onset anaphylaxis without early-phase responses. However, the relevant allergens of natto allergy have never been identified. CASE SUMMARY: A 38-year-old man developed an anaphylactic reaction accompanied by flashing, generalized urticaria, conjunctival redness, and dyspnea 3 hours after ingestion of commercial cold Chinese noodles. He had avoided natto for the past year due to developing several anaphylactic reactions half a day after natto ingestion. The results of skin prick tests (SPTs) were strongly positive for natto and the soup of cold Chinese noodles. Furthermore, SPTs showed positive for poly (γ-glutamic acid) (PGA), which is a major constituent of natto mucilage, alone among all the ingredients of the cold Chinese noodle soup. Therefore, he was diagnosed with late-onset anaphylaxis to PGA contained in natto and the cold Chinese noodle soup. DISCUSSION: These results indicated that in the present case, the relevant allergen of late-onset anaphylaxis may have been PGA in all episodes and that the patient had been sensitized by PGA through natto ingestion. PGA is produced by Bacillus subtilis during fermentation and is a high-molecular, biodegradable polymer. The late onset is therefore, hypothesized to be due to a delayed absorption of PGA, as PGA biodegrades to peptides sufficiently small to be absorbed in the bowel. PGA has recently been applied to a wide range of fields such as foods, cosmetics, and medicine. Therefore, patients with late-onset anaphylaxis to PGA of natto should avoid not only natto but also other materials containing PGA.

Statistical analysis of Stevens-Johnson syndrome caused by Mycoplasma pneumonia infection in Japan.

BACKGROUND: Stevens-Johnson syndrome (SJS) associated with Mycoplasma pneumoniae (M. pneumoniae) infection is mainly observed in children. In adults, drugs are a major cause of SJS, but some adult patients with SJS are infected with M. pneumoniae. We analyzed patients with SJS associated with M. pneumoniae infection to elucidate the differences between drug-induced SJS and M. pneumoniae-associated SJS and also to study differences between M. pneumoniae-associated SJS in children and adults. METHODS: This is a retrospective review of Japanese patients who have been reported as M. pneumoniae-associated SJS in medical Journals published from 1981 to 2009, compared with data of Japanese patients with drug-induced SJS reported from 2000 to 2009. RESULTS: Thirty-eight cases of M. pneumoniae-associated SJS and 78 cases of drug-induced SJS were analyzed in this study. Ocular lesions were observed more frequently in M. pneumoniae-associated SJS than in drug-induced SJS (p < 0.01), and adult patients showed a higher ratio of sequelae in their eyes than did patients under 20 years of age (p < 0.01). Sixty-six percent of adult patients with M. pneumoniae-associated SJS developed fever/respiratory symptoms and mucocutaneous lesions on the same day. In contrast, most of the patients under 20 years of age developed fever/respiratory symptoms before mucocutaneous involvement. This means that these adult patients were infected and immunized previously and developed allergic reactions to M. pneumoniae soon after the later infection. CONCLUSIONS: In order to prevent ocular sequelae in adult patients when M. pneumoniae infection is suspected, more intensive treatment may be needed in adult patients than in younger patients.

Japanese guideline for atopic dermatitis.

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.

[National prevalence survey of hereditary angioedema in Japan].

BACKGROUND: The prevalence of hereditary angioedema (HAE) is estimated to be approximately 1 case per 50000 persons in English literatures. However, neither disease prevalence nor epidemiologic features of HAE has been surveyed in Japan. METHODS: A nation-wide prevalence survey of HAE in Japan was conducted in 2009. We mailed questionnaires to hospitals with 200 or more beds (1389 hospitals and 5240 departments including Dermatology, Otolaryngology, Emergency Medical Care, Internal Medicine, Pulmonary Medicine, Allergy & Rheumatology), to ask numbers, disease types, symptoms and treatments of angioedema of patients visited to their hospitals. RESULTS: In total, 1128 replies were obtained and 411 patients of angioedema including 52 HAE type1 or type2 patients were reported. In the HAE type1 or type2 patients, 54% patients have experienced cutaneous swelling on face, 42% patients have experienced throat discomfort and 37% had experienced abdominal symptoms. In acute attacks of HAE, 29% patients had been treated with C1-inhibitor concentrates. CONCLUSION: The prevalence of HAE in Japan may be lower than the estimated prevalence mainly in Europe and North America. Many patients with HAE may not be appropriately treated especially for their acute attacks. Further studies by genomic analysis should be performed to reveal the penetrance of the C1 inhibitor gene deficiency and occurrence of HAE type3 in Japan.

[Analysis of 76 patients with urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Japan].

BACKGROUND: The pathogenesis of urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still obscure. We analyzed the clinical characteristics of patients with NSAIDs-induced urticaria and angioedema without asthma in Japan. METHODS: We retrospectively collected the cases of NSAIDs-induced urticaria and angioedema from Japanese medical journals in 2000-2009. RESULTS: Seventy-six patients were analyzed. The male/female ratio was 1:2.5 and the mean age was 38.1 years. Urticaria was most frequent clinical manifestation in 3 groups; urticaria alone, urticaria and angioedema, and angioedema alone. Time interval from drug administration to onset was 5 minutes to 48 hours by aspirin at a dose of 25-1000 mg. Skin prick test was performed with aspirin in 33 patients, and the results were negative in all patients. Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, and celecoxib, a new selective COX-2 inhibitor, were administered safely in 4 of 6 patients and in 2 of 3 patients with NSAIDs-induced urticaria, respectively. These drugs were administered safely in all administered patients with NSAIDs-induced angioedema. Tiaramidehydrochroride (a basic COX-1 inhibitor) was safely used in 23 administered patients with NSAIDs-induced angioedema. Leukotriene receptor antagonists were effective in 2 of 5 patients administered, but aggravated symptoms in the others. CONCLUSION: Diversity of NSAIDs-induced urticaria and angioedema was shown in this study. Pathogenesis of NSAIDs-induced urticaria and angioedema without asthma seems to be different from that of NSAIDs-induced asthma.

HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Recently, strong associations of HLA-B*1502 with carbamazepine-induced SJS/TEN have been found in Han Chinese patients. These associations have been confirmed in several Asian populations, excluding Japanese. SJS patients carrying HLA-B*1508, HLA-B*1511, or HLA-B*1521, which are members of the HLA-B75 type along with HLA-B*1502, were detected in studies in India and Thailand. In the current study, we genotyped the HLA-B locus from 14 Japanese typical and atypical SJS/TEN patients in whom carbamazepine was considered to be involved in the onset of adverse reactions. Although there were no HLA-B*1502 carriers, four patients had HLA-B*1511. Our data suggest that HLA-B*1511, a member of HLA-B75, is a risk factor for carbamazepine-induced SJS/TEN in Japanese.

Molecular cloning, expression, and characterization of a major 38-kd cochineal allergen.

BACKGROUND: Carmine is a natural red pigment obtained from dried gravid female cochineal insects (Dactylopius coccus or Coccus cacti). There have been several reports of allergies to carmine, but the major allergens responsible have not been identified. OBJECTIVE: To identify the major allergenic proteins in cochineal. METHODS: Immunoblots of purified cochineal extract were probed with sera from 3 patients with allergy. Partial amino acid sequences were determined for the proteins bound by IgE, and the corresponding cDNA, containing a complete coding region, was cloned by 5' and 3' rapid cDNA extension and PCR. The recombinant protein was expressed in yeast and subjected to immunoblotting. RESULTS: We identified a full-length cDNA encoding a protein, which we named CC38K, with 335 amino acids and a molecular mass calculated as 38 kd. This amino acid sequence included all the partial amino acid sequences obtained from the purified proteins identified by IgE from patients with allergy. Recombinant CC38K protein was recognized by patients' sera, indicating that this is a major allergen present in carmine. The CC38K sequence showed homology to phospholipases. CONCLUSION: We have, for the first time, identified the major allergen in cochineal extract. This protein may be a phospholipase or related enzyme, both of which are known to be allergens in other insects.