Chronic urticaria due to autoreactivity to progesterone.

A 23-year-old, regularly menstruating woman presented with recurrent urticarial eruptions, which occurred premenstrually. A skin prick test was positive for progesterone, but the urticaria was unresponsive to standard treatments. The patient was treated with goserelin (Zoladex), which suppressed her menstrual cycle, leading to the resolution of her symptoms. Subsequent flares were controlled by further goserelin injections, and the urticaria is currently in remission. However, the risks of inducing menopause artificially are significant, and alternative long-term solutions may need to be considered in the event of a relapse.

Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report.

Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1-5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Nonsedating H1-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in < 50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H1 -antihistamines. Consequently, there is a great need for new therapeutic strategies.

Pruritus is a common and significant symptom of acne.

BACKGROUND: Acne is a common condition in both adolescents and adults. Characteristics of acne are well described, but itch is rarely mentioned as a clinical feature. Pruritus could be a significant contributory factor to the burden of disability in patients with acne. OBJECTIVE: We examine the prevalence of pruritus and its clinical attributes in patients with acne in an outpatient clinic. STUDY DESIGN: Descriptive study over a 15 month period from October 2005 to December 2006. PATIENTS AND METHODS: 120 consecutive patients with acne attending an outpatient clinic at National Skin Centre, Singapore were recruited. Pruritus was evaluated using a validated questionnaire. Severity of acne was determined using FDA Global Acne Grading. RESULTS: 84 patients (70%) reported itch in acne. Patients who experienced itch in acne tended to be slightly older (p = 0.05). Majority of patients (83%) reported itch at noon and most experienced itch on a transient nature. The most common descriptor of itch was tickling (68%). Severity of pruritus in acne was comparable to mosquito-bite and it significantly affected patients' mood (55%). Common aggravating factors for the pruritus were sweat (71%), heat (62%) and stress (31%). A significant proportion of patients with itch (52%) had scratched or rubbed the affected area while 37% would wash the area to find relief. CONCLUSION: Our results suggest that itch is a common and significant symptom in acne. Acne patients experienced considerable disability due to the associated pruritus.

Chronic idiopathic urticaria with functional autoantibodies: 12 years on.

It is now recognized that approximately one-third of patients with chronic idiopathic urticaria (CIU) have histamine-releasing autoantibodies directed against either the high-affinity IgE receptor or, less frequently, against IgE. However, there are several unsolved problems relating to the role of such autoantibodies in the disease. Additionally, it is not clear whether CIU with autoantibodies can be classified as an autoimmune disease. The detection of patients with autoantibodies also poses challenges. Firstly, the only in vivo method, the autologous serum skin test, is at best 80% sensitive and specific using in vitro basophil histamine release assays as the verum. Secondly, in vitro tests are only done in a small number of research laboratories, and are not widely commercially available, and thirdly, there is some divergence between results obtained by different methods (functional and immunoassays) used to detect patients with autoantibodies. The presence of autoantibodies may be important clinically in a small group of severely affected, treatment-resistant patients, where immunomodulatory treatments may be helpful.

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).

EAACI/GA2LEN/EDF guideline: management of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).

Thyroid autoimmunity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

Itch: scratching more than the surface.

In origin, itch can be cutaneous ("pruritoceptive", e.g. dermatitis), neuropathic (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or psychogenic. Although itch of cutaneous origin shares a common neural pathway with pain, the afferent C-fibres subserving this type of itch are a functionally distinct subset: they respond to histamine, acetylcholine and other pruritogens, but are insensitive to mechanical stimuli. Histamine is the main mediator for itch in insect bite reactions and in most forms of urticaria, and in these circumstances the itch responds well to H(1)-antihistamines. However, in most dermatoses and in systemic disease, low-sedative H(1)-antihistamines are ineffective. Opioid antagonists relieve itch caused by spinal opioids, cholestasis and, possibly, uraemia. Ondansetron relieves itch caused by spinal opioids (but not cholestasis and uraemia). Other drug treatments for itch include rifampicin, colestyramine and 17-alpha alkyl androgens (cholestasis), thalidomide (uraemia), cimetidine and corticosteroids (Hodgkin's lymphoma), paroxetine (paraneoplastic itch), aspirin and paroxetine (polycythaemia vera) and indometacin (some HIV+ patients). If the remedies specified fail, paroxetine and mirtazapine should be considered. Ultraviolet B therapy, particularly narrow-band UVB, may be superior to drug treatment for itch in uraemia.

Methotrexate-responsive chronic idiopathic urticaria: a report of two cases.

Chronic idiopathic urticaria (CIU) may be severe and refractory to standard therapies. We describe two patients with CIU, neither of whom had detectable autoantibodies, in whom control of the disease was achieved with methotrexate.

Antihistamines.

In the 1990s, major improvements occurred in the therapeutic index of H1 antihistamines. The third-generation compounds promise to be more effective and nontoxic. The future major advances are likely to result from development and exploitation of non-H1 receptor-mediated antiallergic actions of these drugs.

Definition, classification, and routine diagnosis of urticaria: a consensus report.

Urticaria is a well-known disease entity; however, with an increasing understanding of the molecular mechanisms involved in its pathogenesis, there is also growing evidence for a heterogeneity of urticaria. Currently it is sometimes difficult to compare divergent data reported by different centers researching urticaria due to a lack of precisely described patient populations. A consensus definition and classification of the disease and its subtypes, taking into account new developments, are therefore needed. In addition, this consensus report provides a guideline for diagnostic procedures in different subtypes of urticaria.

Management of urticaria: a consensus report.

This consensus report is the result of a panel discussion during the International Clinically Oriented ESDR Symposium Urticaria 2000. Urticaria has a profound impact on the quality of life and effective treatment is required. The most important are nonsedating H1 antihistamines. They have been proven to be effective in double-blind controlled studies, but concentrations higher than those recommended may be necessary. Due to different urticaria subtypes and the individual variation in the course of the disease and response to treatment, however, alternative therapies may be required. Immunosuppressive drugs like cyclosporine A and corticosteroids should not be used long term due to undesirable side-effects.