Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1-antihistamines for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with H1-antihistamines versus H1-antihistamines alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched MEDLINE, Embase, CENTRAL, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, FDA, and EMA databases from inception to December 18th, 2023 for randomized controlled trials (RCTs) evaluating antileukotrienes and H1-antihistamines versus H1-antihistamines alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. Open Science Framework registration: https://osf.io/h2bfx/. RESULTS: Thirty-four RCTs enrolled 3,324 children and adults. Compared to H1-antihistamines alone, the combination of a leukotriene receptor antagonist (LTRA) with H1-antihistamines probably modestly reduces urticaria activity (mean difference: -5.04, 95%CI -6.36 to -3.71; 7-day Urticaria Activity Score) with moderate certainty. We made similar findings for itch and wheal severity, and quality of life. Adverse events were probably not different between groups (moderate certainty), however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding LTRAs to H1-antihistamines probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with LTRAs is small and uncertain.

Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear. OBJECTIVE: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids. METHODS: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. RESULTS: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty). CONCLUSIONS: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more.

Breast Cancer Treatment.

Breast cancer is the leading cause of death from cancer in women worldwide, and the second most common cause of death from cancer in women in the United States. Risk assessment tools can identify the risk of breast cancer, and patients at high risk may be candidates for risk-reducing medications. The choice of medication varies with menopausal status. Breast cancer treatment depends on the stage. Stage 0 is ductal carcinoma in situ, which is noninvasive but progresses to invasive cancer in up to 40% of patients. Ductal carcinoma in situ is treated with lumpectomy and radiation or with mastectomy. If ductal carcinoma in situ is estrogen receptor-positive, patients may also receive endocrine therapy. Early invasive stages (I, IIa, IIb) and locally advanced stages (IIIa, IIIb, IIIc) are nonmetastatic and have three treatment phases. The preoperative phase uses systemic endocrine or immunotherapies when tumors express estrogen, progesterone, or ERBB2 receptors. Preoperative chemotherapy may also be used and is the only option when tumors have none of those three receptors. There are two options for the surgical phase with similar survival rates; a lumpectomy with radiation if the tumor can be excised completely with good cosmetic results, or a mastectomy. Sentinel lymph node biopsy is also performed when there is suspected nodal disease. The postoperative phase includes radiation, endocrine therapy, immunotherapy, and chemotherapy. Postmenopausal women should also be offered postoperative bisphosphonates. Stage IV (metastatic) breast cancer is treatable but not curable. Treatment goals include improving the length and quality of life.

Erythema Multiforme: Recognition and Management.

Erythema multiforme is an immune-mediated reaction that involves the skin and sometimes the mucosa. Classically described as target-like, the erythema multiforme lesions can be isolated, recurrent, or persistent. Most commonly, the lesions of erythema multiforme present symmetrically on the extremities (especially on extensor surfaces) and spread centripetally. Infections, especially herpes simplex virus and Mycoplasma pneumoniae, and medications constitute most of the causes of erythema multiforme; immunizations and autoimmune diseases have also been linked to erythema multiforme. Erythema multiforme can be differentiated from urticaria by the duration of individual lesions. Erythema multiforme lesions are typically fixed for a minimum of seven days, whereas individual urticarial lesions often resolve within one day. Erythema multiforme can be confused with the more serious condition, Stevens-Johnson syndrome; however, Stevens-Johnson syndrome usually contains widespread erythematous or purpuric macules with blisters. The management of erythema multiforme involves symptomatic treatment with topical steroids or antihistamines and treating the underlying etiology, if known. Recurrent erythema multiforme associated with the herpes simplex virus should be treated with prophylactic antiviral therapy. Severe mucosal erythema multiforme can require hospitalization for intravenous fluids and repletion of electrolytes.

Annular Lesions: Diagnosis and Treatment.

Annular lesions can present in a variety of diseases. Knowledge of the physical appearance and history of presentation of these skin findings can help in the diagnosis. A pruritic, annular, erythematous patch that grows centrifugally should prompt evaluation for tinea corporis. Tinea corporis may be diagnosed through potassium hydroxide examination of scrapings. Recognizing erythema migrans is important in making the diagnosis of Lyme disease so that antibiotics can be initiated promptly. Plaque psoriasis generally presents with sharply demarcated, erythematous silver plaques. Erythema multiforme, which is due to a hypersensitivity reaction, presents with annular, raised lesions with central clearing. Lichen planus characteristically appears as planar, purple, polygonal, pruritic papules and plaques. Nummular eczema presents as a rash composed of coin-shaped papulovesicular erythematous lesions. Treatment is aimed at reducing skin dryness. Pityriasis rosea presents with multiple erythematous lesions with raised, scaly borders, and is generally self-limited. Urticaria results from the release of histamines and appears as well-circumscribed, erythematous lesions with raised borders and blanched centers. Annular lesions occur less commonly in persons with fixed drug eruptions, leprosy, immunoglobulin A vasculitis, secondary syphilis, sarcoidosis, subacute cutaneous lupus erythematosus, and granuloma annulare.

Edema: diagnosis and management.

Edema is an accumulation of fluid in the interstitial space that occurs as the capillary filtration exceeds the limits of lymphatic drainage, producing noticeable clinical signs and symptoms. The rapid development of generalized pitting edema associated with systemic disease requires timely diagnosis and management. The chronic accumulation of edema in one or both lower extremities often indicates venous insufficiency, especially in the presence of dependent edema and hemosiderin deposition. Skin care is crucial in preventing skin breakdown and venous ulcers. Eczematous (stasis) dermatitis can be managed with emollients and topical steroid creams. Patients who have had deep venous thrombosis should wear compression stockings to prevent postthrombotic syndrome. If clinical suspicion for deep venous thrombosis remains high after negative results are noted on duplex ultrasonography, further investigation may include magnetic resonance venography to rule out pelvic or thigh proximal venous thrombosis or compression. Obstructive sleep apnea may cause bilateral leg edema even in the absence of pulmonary hypertension. Brawny, nonpitting skin with edema characterizes lymphedema, which can present in one or both lower extremities. Possible secondary causes of lymphedema include tumor, trauma, previous pelvic surgery, inguinal lymphadenectomy, and previous radiation therapy. Use of pneumatic compression devices or compression stockings may be helpful in these cases.

Bedbug infestation.

The significant resurgence of bedbugs in the past decade has been attributed to pesticide resistance, more frequent travel, lack of public awareness, and inadequate pest control programs. Bedbugs are obligate blood parasites (insect family Cimicidae). They can withstand a large range of temperatures but are attracted to warmth and carbon dioxide. They typically feed just before dawn. Cutaneous reactions to bedbug bites can include macules, papules, wheals, vesicles, bullae, and nodules. Bites may be confused with other skin conditions. Bedbug bite reactions are typically self-limited and resolve within one to two weeks without treatment. Bedbug infestation may cause significant psychological distress. The diagnosis of a bedbug infestation is based on history, appearance of bites, and inspection of sleeping quarters. Although there is no evidence that bedbugs transmit disease, systemic reactions may include asthma, angioedema, generalized urticaria, iron deficiency anemia, and, rarely, anaphylaxis. An integrated pest management strategy should be employed to eliminate infestation. Tactics include vacuuming, heat or cold treatment, trapping devices, and pesticides.

Evaluation of nail abnormalities.

Knowledge of the anatomy and function of the nail apparatus is essential when performing the physical examination. Inspection may reveal localized nail abnormalities that should be treated, or may provide clues to an underlying systemic disease that requires further workup. Excessive keratinaceous material under the nail bed in a distal and lateral distribution should prompt an evaluation for onychomycosis. Onychomycosis may be diagnosed through potassium hydroxide examination of scrapings. If potassium hydroxide testing is negative for the condition, a nail culture or nail plate biopsy should be performed. A proliferating, erythematous, disruptive mass in the nail bed should be carefully evaluated for underlying squamous cell carcinoma. Longitudinal melanonychia (vertical nail bands) must be differentiated from subungual melanomas, which account for 50 percent of melanomas in persons with dark skin. Dystrophic longitudinal ridges and subungual hematomas are local conditions caused by trauma. Edema and erythema of the proximal and lateral nail folds are hallmark features of acute and chronic paronychia. Clubbing may suggest an underlying disease such as cirrhosis, chronic obstructive pulmonary disease, or celiac sprue. Koilonychia (spoon nail) is commonly associated with iron deficiency anemia. Splinter hemorrhages may herald endocarditis, although other causes should be considered. Beau lines can mark the onset of a severe underlying illness, whereas Muehrcke lines are associated with hypoalbuminemia. A pincer nail deformity is inherited or acquired and can be associated with beta-blocker use, psoriasis, onychomycosis, tumors of the nail apparatus, systemic lupus erythematosus, Kawasaki disease, and malignancy.

Q & A: patient to physician FAQs: answers to common patient questions about vaccinations.

This article outlines common questions about vaccinations that patients ask their physicians and provides answers to those questions.