Dermal Reactions Research Articles

Antibody and cytokine levels in humans fed on by the common bedbug, Cimex lectularius L.

Little is known about cimicosis, the resultant dermal reaction from feeding activity by the common bedbug, Cimex lectularius L. We fed C. lectularius on human study subjects four times over four weeks and measured serum cytokine and antibody levels, and subjects recorded any cimicosis. The average time for subjects to develop cimicosis decreased with each feeding from 8.4, to 2.1, 1.5 and 1.3days, respectively. There were no significant changes in total IgG, IgG1, IgG2, IgG4 or IgE levels between the first and fourth bedbug feedings, but there was a significant decrease in total IgG3 levels (P<.001). IgG4 was not required for cimicosis. Higher IgG2 and IgG4 levels at study visit 4 were associated with an increased duration of cimicosis (P=.04) and lower pruritis (P=.03), respectively. There were no significant changes in serum TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10, IFN-γ and IL-17A levels before and one hour after the C. lectularius feeding. Lower post-C. lectularius feeding IL-6 levels were associated with increased pruritis (P=.001) and the time to maximum pruritis (P=.04), respectively. Higher post-C. lectularius feeding IL-5 levels were associated with a longer duration of pruritis (P=.05).

Unraveling the role of preexisting immunity in prostate cancer patients vaccinated with a HER-2/neu hybrid peptide

BackgroundCancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported...

Dermal reactivity and resilience in a sample of depressed patients

BackgroundMental disorders are considered a risk factor for suicide: for example, the lifetime risk of suicide is estimated to be 4%–8% in people with mood disorders. The literature suggests that a history of suicide attempts is significantly related to electrodermal hyporeactivity and that patients with violent suicide attempters exhibit faster habituation of the electrodermal response to repeated neutral tones than patients with non-violent attempts. The impact of depressive symptoms on suicidal ideation may be moderated by resilience. Resilience refers to the ability to maintain o regain mental health despite experiencing adversity. In bipolar and depressive disorders, resilience may influence severity of episodes, frequency of relapse and response to treatment.AimThe objective of our study was to assess the possible correlation among attempted suicide, resilience and dermal reactivity in a sample of depressed patients.MethodsWe recruited patients with depressive disorders and bipolar depression; data about socio-demographic, clinical features, severity of attempted suicide and suicidal risk were gathered. Patients filled in the Resilience Scale for Adult (RSA). Moreover, for each patient we performed the Edor test in order to assess dermal reactivity.ResultsData collection is still ongoing. We expect to find lower levels of resilience in those patients who are hyporeactive and attempted suicide. Moreover, we hypothesize that suicide attempts in the group of hyporeactive patients would be characterized by planning and greater severity. Clinical implications will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Comparison of Unintentional Exposures to Codeine and Hydrocodone Reported to Texas Poison Centers

BackgroundHydrocodone has recently been reclassified as a Schedule II drug by the United States Drug Enforcement Administration and Food and Drug Administration in order to curtail prescription drug abuse. There is concern that analgesic substitutes, such as codeine, will not be as safe or effective. ObjectiveThe purpose of this study is to compare the demographics, adverse events, and medical outcomes of patients who had unintentional hydrocodone or codeine exposures through the use of a state's poison center database. MethodsThe Texas Poison Center Network's database was utilized to find all reported unintentional ingestions or adverse reactions of products containing codeine or hydrocodone. Comparisons were made between the two medications by calculating the rate ratios (RR) and 95% confidence intervals (CI). ResultsChildren aged 5 years or younger were more exposed to codeine (51.6%). Hydrocodone exposures had more serious outcomes (11% vs. 9%; RR = 0.82; 95% CI 0.73–0.91) and had more nausea (7.1% vs. 2.8%; RR = 0.4; 95% CI 0.32–0.48) and vomiting (6.5% vs. 3.3%; RR = 0.51; 95% CI 0.43–0.62). Hydrocodone had a higher rate of intravenous fluids administration (2.4% vs. 1.7%; RR = 0.71; 95% CI 0.54–0.92) and antiemetics (0.4% vs. 0.1%; RR = 0.23; 95% CI 0.08–0.64). Codeine was more closely associated with dermal reactions and patients were given antihistamines (2.5% vs. 1.3%; RR = 1.88; 95% CI 1.46–2.41) more frequently. Cardiovascular side effects, ataxia, and headache occurred equally between the groups. ConclusionsBoth drugs had a wide array of reported side effects, but the overall incidence of serious outcomes was low.

Ibrutinib-Treated Platelets Secure Vascular Integrity in Inflammation

Background: Ibrutinib is a potent and irreversible inhibitor of Bruton's tyrosine kinase (Btk), and has been approved for treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In recent clinical trials, Ibrutinib has shown high efficacy with an excellent safety profile. However, bleeding events have been observed in a subset of patients in several of these trials. While these bleeding events are generally low grade and have not led to interruption or dose reduction of treatment, the origin of bleeding remains incompletely understood. In the setting of thrombocytopenia, inflammation can induce robust vascular permeability and hemorrhage, and our lab has previously shown that immunoreceptor tyrosine-based activation motif (ITAM) signaling is necessary for the protective effects of platelets against hemorrhage. In platelets Btk acts downstream of ITAM receptors, therefore we hypothesized that bleeding in Ibrutinib-treated patients may be, at least in part, the result of hemorrhage at sites of inflammation.Methods: To investigate the possibility that bleeding events in Ibrutinib-treated patients are due to inflammatory hemorrhage, we used two inflammatory models - the dermal reverse passive Arthus reaction (rpA) and P. aeruginosa LPS-induced lung inflammation, both of which have been shown to induce hemorrhage in the absence of platelet ITAM signaling. To selectively inhibit Btk in platelets, thrombocytopenic mice were reconstituted with Ibrutinib- or vehicle-treated wild-type platelets and challenged in rpA or LPS model. Bleeding in the dermis or broncho-alveolar lavage (BAL) fluid was assessed by analysis of hemoglobin. In the clinic, patients generally receive once-a-day doses of 420-560 mg of the Btk inhibitor Ibrutinib, and plasma concentrations can transiently reach 0.5-1 µM. Thus, during their lifetime, circulating platelets are exposed to compounding doses of Ibrutinib, which may have greater inhibitory effects than a single dose, a phenomenon which we have observed in mice (see results below). Therefore, we treated mouse platelets in vitro with 0.5 µM Ibrutinib (low dose, equal to a single dose) or 5 µM Ibrutinib (high dose, comparable to multiple dose exposure) before adoptive transfer into mice.Results: While low dose Ibrutinib did not prevent αIIbβ3 integrin activation induced by collagen or convulxin (Cvx), high dose Ibrutinib abolished collagen-induced aggregation. This dose-dependent inhibition of aggregation was also observed in platelets isolated from mice which had received a single vs. multiple doses of Ibrutinib in vivo. αIIbβ3 activation induced by the stronger GPVI agonist, Cvx, however was only partially impaired, suggesting that Ibrutinib may not completely inhibit ITAM-dependent platelet activation. We next tested whether platelets treated ex vivo with Ibrutinib and transfused into thrombocytopenic mice were able to secure vascular integrity at sites of inflammation. In both models, platelet depletion without transfusion of wild-type platelets induced substantial bleeding. However, transfusion of Ibrutinib-treated platelets was able to rescue bleeding to the same extent as vehicle-treated platelets.Summary: Our findings demonstrate that Ibrutinib-treated platelets are capable of securing vascular integrity at sites of inflammation in mice. Our studies suggest that bleeding events in patients treated with Ibrutinib are not due to inflammation-associated hemorrhage. DisclosuresBergmeier:AHA: Research Funding; NIH: Research Funding.

Evaluation of BCG Vaccine in Excessive Dermal Reactivity Test

BCG vaccine has been in use globally to control the tuberculosis since the year 1921 and there has been significant achievement to curtail the disease. The important tests as per pharmacopoeial requirements including count of viable units (CVU) and excessive dermal reactivity (EDR) are required to be performed for ensuring the quality of BCG vaccine. In order to see the trend analysis of EDR of BCG vaccine used in India, a study has been carried out using 35 batches of BCG vaccine manufactured by two different manufacturers. The results of EDR of 16 batches of manufacturer-1 and 19 batches from manufacturer-2 ranged from 2.7mm to 3.2mm and1.9mm to 3.9mm respectively and the results are not markedly different from that of reference vaccine. The preliminary observation based on 16 batches suggests that there is some correlation between CVU and EDR of BCG vaccine, however more batches of BCG vaccine need to be tested to draw a clear correlation between these two tests. The critical EDR test is required to be performed regularly till the suitable alternate in vitro method is established. Overall results of the study suggest that BCG vaccine used in India is safe and potent.

Evaluation of histopathological features of Argas reflexus bite in pigeon

Argas reflexus is considered obligate blood feeder that may cause skin redness and local swelling. For histopathological evaluation of biting site, pigeons were used as natural host species in this study. Adult ticks were collected from Urmia, North-west of Iran and kept in a desiccator before their use in the experiment. Sixteen Pigeons were infested experimentally and were divided into 4 groups, euthanized after 30 min, 4, 24 and 48h for evaluation of histopathological changes in biting sites. Early histopathologic lesions due to time of infestation included edema, hemorrhagic foci, vascular congestion, necrosis and mild to severe inflammatory reaction in dermis. In late lesions, presence of micro abscess foci in dermis was prominent. This study well documented the different pathological changes of skin of pigeons with Argas reflexus. However, further study should be performed to evaluate allergic immune responses and pathological changes in other animal species including human.

The establishment of sub-strain specific WHO Reference Reagents for BCG vaccine

As the latest addition to the sub-strain specific WHO Reference Reagents of BCG vaccine, an international collaborative study was completed to evaluate the suitability of a candidate BCG Moreau-RJ sub-strain as a WHO Reference Reagent of BCG vaccine. This follows the recent replacement of the WHO 1st International Reference Preparation for BCG vaccine, by three sub-strain specific WHO Reference Reagents of BCG vaccine (Danish 1331, Tokyo 172-1 and Russian BCG-I) in order to complete the coverage of most predominant sub-strains used for BCG vaccine production and distribution for use worldwide. The study used cultural viable count and modified ATP assays to quantify the preparation and multiplex PCR to confirm the identity of the sub-strain. The establishment of this WHO Reference Reagent of BCG vaccine of Moreau-RJ sub-strain was approved by the WHO Expert Committee on Biological Standardization meeting in October 2012. This preparation is available for distribution by NIBSC-MHRA, UK. The data from real-time stability monitoring demonstrated that these Reference Reagents of BCG vaccine are very stable in storage condition at −20°C. They serve as the valuable source of BCG Reference Reagents for use as comparators (1) for viability assays (such as cultural viable count and modified ATP assays); (2) for in vivo assays (such as the absence of virulent mycobacteria, dermal reactivity and protection assays) in the evaluation of candidate TB vaccines in non-clinical models; (3) for identity assays using molecular biology techniques.

Specific Cutaneous Involvement in Whipple Disease

Cutaneous lesions in Whipple disease (WD) are infrequent, and the histological findings are usually nonspecific. Specific cutaneous lesions have rarely been described and usually involve the subcutaneous fat. We report a patient diagnosed with WD, who developed multiple small subcutaneous nodules after antibiotic treatment was administered. In addition to septal panniculitis, the cutaneous biopsy showed a mild granulomatous dermal reaction with PAS-positive macrophages characteristic of WD. A positive polymerase chain reaction in the cutaneous sample confirmed the presence of Tropheryma whipplei in the skin. Dermatopathologists should be aware that not only subcutaneous lesions but also dermal lesions may exhibit specific findings of WD.

Orofacial dermal fillers: foreign body reactions, histopathologic features, and spectrometric studies

The aim of this study is to assess the different histopathologic presentations of dermal filler materials-induced foreign body reactions by spectrometric analyses. Sixteen cases of dermal filler foreign body reactions in the orofacial region were retrieved from the 2006-2013 period. The histologic features were evaluated and categorized into 5 groups (I to V). Unstained deparaffinized sections of representative tissue from one case in each of groups I to IV were sent for spectrometric analysis, along with samples of 2 popular dermal fillers (Juvéderm and Radiesse). With the help of spectrometric analysis, we were able to correlate the histopathologic presentations with the specific type of dermal filler used.

Pre-Bullous changes in bullous lupus erythematosus

We are presenting here an interesting case of pre-bullous biopsy in a patient going on to develop bullous lupus erythematosus. This is a 45-year-old female patient who is a known case of lupus nephritis on treatment since 2007, who presented with a 4-month history of persistent erythematous plaques in the body and limbs. The biopsy of the lesion in the forearm showed an unusual neutrophilic dermatosis with both interstitial dermal component and prominent neutrophilic interface reaction to epidermis, suspected to be systemic lupus erythematosus (SLE) associated. The immunofluorescence was consistent with known diagnosis of SLE. The patient presented with a blister on the ankle 2 months later, the histology of which was consistent with bullous SLE. The pre-bullous appearances have not been described in detail in the literature. This is to compare the histology at the pre-bullous stage of the disease with other non-connective tissue associated rashes. The histological features combined with the immunofluorescence might help to attribute the rash to the patient’s lupus even before clinical blistering, so that the treatment can be streamlined.

The discovery of a hybrid population of mosquitoes of the Culex pipiens L. complex (Diptera, Culicidae) on the Kos Island (Greece) by means of molecular markers

The mosquitoes attacking humans in hotel rooms on the Kos Island (Greece) were identified by means of several molecular markers and proved to be hybrids of Culex pipiens and C. quinquefasciatus. The former species is a typical local inhabitant, whereas the latter was probably introduced with some transport from a more southern region. The mosquitoes were anthropophilic, and their bites induced strong lasting allergic dermal reaction.

Direct comparison of laser Doppler flowmetry and laser Doppler imaging for assessment of experimentally-induced inflammation in human skin

Laser Doppler imaging (LDI) and laser Doppler flowmetry (LDF) can measure localized skin perfusion. The purpose of the study was to directly compare LDF with LDI as a tool for measuring skin blood changes in an experimental model of chemically-induced skin inflammation. Regions of interest 1.8 cm² in area on the forearm skin of eight healthy volunteers were randomized and exposed to 0.25, 0.5, 1, or 2 % topical sodium lauryl sulfate (SLS) or vehicle for 24 h. Mean blood flow was measured by LDI and LDF at 24, 48, and 72 h. Inflammation was clinically graded using a standardized, clinical score. Sodium lauryl sulfate induced significant, dose-dependent local inflammation. Both Doppler methods were significantly correlated with the clinical grading (LDF, r = 0.755; LDI, r = 0.836). LDF and LDI showed similar significance differences with regard to dose- and time-response patterns compared to the vehicle. The absolute and relative LDF and LDI values were significantly correlated. Laser Doppler flowmetry and LDI showed similar dose- and time-response relations in irritant-induced inflammatory skin reactions. For the assessment of localized skin reactions, LDI possesses no apparent advantages over the less expensive LDF method for grading dermal inflammatory reactions.

A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome&amp;reg; gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee

ObjectiveTo evaluate the safety and efficacy of ketoprofen in Transfersome® gel (IDEA-033) in comparison with a ketoprofen-free vehicle (TDT 064) for the treatment of osteoarthritis (OA) of the knee.MethodsPatients with knee OA (N = 866) were randomly assigned to receive topical IDEA-033 containing 100, 50, or 25 mg ketoprofen, or TDT 064 twice daily for 12 weeks, in a double-blind trial. The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index pain subscale score. The coprimary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy. The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder rates.ResultsThe WOMAC pain scores were reduced by approximately 50% or more in all four groups. The 100 and 50 mg ketoprofen groups, but not the 25 mg group, showed a superior reduction in the WOMAC pain score versus the TDT 064 group (100 mg: −57.4% [P = 0.0383]; 50 mg: −57.1% [P = 0.0204]; and 25 mg: −53.4% [P = 0.3616] versus TDT 064: −49.5%). The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score, whereas the patient global assessment of 50 mg ketoprofen group, but not the 100 or 25 mg group, was superior to that of the TDT 064 group (P = 0.0283). Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group, but were high in all groups (100 mg: 88.6%; 50 mg: 86.8%; 25 mg: 88.6%; and TDT 064: 77.5%). Dermal reactions were the only relevant drug-related adverse events in all four groups.ConclusionThe 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA. The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064.

Dermatologic toxicities to targeted cancer therapy: shared clinical and histologic adverse skin reactions

Dermatologic toxicities (DT) to targeted cancer therapy may present as inflammatory dermatoses, keratoses, and as benign and malignant squamous proliferations. Published reports of DT with cancer therapy with epidermal growth factor receptor (EGFR), tyrosine kinase (TK), MEK, PI3K, AKT, and BRAF inhibitors were reviewed. DT associated with targeted cancer therapy demonstrated similar reactions and may be grouped as (i) DT as cutaneous inflammation, and (ii) DT as cutaneous epithelial proliferation. EGFR inhibitor, cetuximab, and MEK inhibitors, selumetinib and trametinib, demonstrated papulopustular rash with a suppurative folliculitis in 83%, 93%, and 80% of the patients on therapy, respectively. Common DT with EGFR inhibitors erlotinib and tyrosine kinase inhibitor sorafenib were hand-foot skin reactions in 30-60% of patients on therapy. PI3K inhibitor BKM-120 and AKT inhibitor MK2206 produced maculopapular eruptions seen as dermal hypersensitivity reaction on the skin biopsy. RAF inhibitors vemurafenib and sorafenib were associated with a variety of cutaneous epithelial proliferations (keratosis pilaris, seborrheic keratosis, verruca vulgaris, actinic keratosis, keratoacanthoma, and squamous cell carcinoma. Various anticancer agents may target similar cellular compounds and/or cell signaling pathways thus share similar clinical and histologic features of DT. The knowledge of the overlap of DT with different types of targeted cancer therapy will assist in evaluation of cutaneous reactions.

Booster inoculations of the AE37 peptide vaccine enhance immunological responses in a phase II study.

3095 Background: We are conducting a multicenter randomized phase II trial of AE37, the Ii-Key hybrid peptide of HER2 776-790 (AE36). The purpose of the study is to determine if the AE37 vaccine can prevent recurrence in disease-free conventionally treated node-positive (NP) and high-risk node-negative (NN) breast cancer patients at significant risk for recurrence. Since clinical efficacy is anticipated to occur as the result of long lasting memory immune responses induced by vaccination, repeated booster inoculations were scheduled as part of the trial. Here we present data on immune responses in patients who received boosters up to 24 months after completion of the primary vaccination series (PVS). Methods: The trial is enrolling NP or high-risk NN patients with any degree of HER2 expression (IHC 1-3+ or FISH &gt; 1.2) rendered disease-free following standard of care therapy. The vaccine group (VG) received AE37+GM-CSF and control group (CG) GM-CSF alone in 6 monthly i.d. inoculations followed by boosters administered every 6 months x 4. Immunologic responses were assessed in vivo by dermal reactions at the inoculation site, and in vitro, against the AE36 peptide, with proliferation and IFN-γ ELISPOT assays. Results: 25 patients in the VG and 23 in the CG have completed their boosters. After the last booster (BRC24), 100%, 54% and 54% in the VG (vs. 9%, 18% and 27% in the CG) responded by dermal reaction, proliferation and IFN-γ ELISPOT, respectively. Mean dermal reactions (orthogonal mean in mm) in vaccinated patients was 25.9±3.13 at completion of the PVS (R6) and increased to 35.47±4.35 at BRC24 (p=0.01). VG patients increased their proliferation response (stimulation index, SI) to AE36 from 0.97±0.046 at baseline (R0) before vaccination to 2.27±0.57 at R6 (p=0.0003) which was maintained until BRC24 (SI 2.21±0,33, p&lt;0.0001). The number of IFN-γ specific spots/106 PBMC increased from 26.88±12.36 at R0 to 40.35±17.02 (p=0.07) at R6, up to 62±16.82 (p=0.0076) at BRC24. Conclusions: Our data demonstrate that AE37 vaccine boosters enhance the immune responses against HER elicited during the PVS, thus sustaining long lasting immunity, a prerequisite for possible clinical efficacy which is currently being evaluated. Clinical trial information: NCT00524277.

Lip Augmentation Dermal Filler Reactions, Histopathologic Features

Instances of perioral and labial foreign body reactions to a variety of injectable dermal fillers were selected from the oral and maxillofacial pathology and dermatopathology archives at Pacific Pathology Laboratory of San Diego with the objective being to engender a compilation of histopathologic characteristics that allow the pathologist to identify the inciting materials. All cases of foreign body reactions located in the lips and perioral regions were reviewed by four pathologists, retaining those cases with a history of injection lip augmentation as well as those with histologic features previously documented to represent dermal filler substances. In selected cases, Alcian blue pH 2.5 with and without hyaluronidase pretreatment was performed. Immunohistochemical markers for macrophages (CD 68), adipocytes (S-100) and keratinocytes (AE1/AE2) were undertaken. All instances presented as single or multiple submucosal plaques, nodules or swellings. Natural polymers including collagen, hyaluronate, hydroxyapatite, poly-L-lactate and synthetic polymers including carboxymethyl cellulose, dimethylpolysiloxane, and polyethyl methacrylate induce histologically unique features that allow for their identification. Host histopathologic responses included nodule without foreign body reaction, nodule with chronic inflammation, granuloma with epithelioid histiocytic and multinucleated giant cell reaction. Dermal filler foreign body host reactions in conjunction with the morphology of the foreign materials themselves are unique and can be differentiated from one another microscopically.

Lupus Miliaris disseminatus faciei: report of a new case and brief literature review

Lupus miliaris disseminatus faciei (LMDF) is a rare dermatosis with characteristic clinicopathological features but of unknown etiolgy. We report a new typical case of LMDF. A 29-year-old man presented with an asymptomatic, micropapular midfacial eruption. Histological examination revealed a dermal granulomatous reaction with central areas of necrosis and occasionally degenerated hair follicles. Workup for sarcoidosis was negative. A moderate improvement was achieved with systemic treatment with doxycycline. A brief overview of the main features of LMDF is presented.

Observations on Healing Process of Wall Ulcers with Concurrent Digital Dermatitis in 52 Cattle: Gross and Light Microscopic Pathology

This paper describes the healing process of the axial and abaxial wall ulcers in cases of concurrent digital dermatitis by gross, histopathologic and therapeutic implications. Fifty two cases showed wall ulcers (13%); the prevalence rate of affected cases by abaxial wall ulcer and axial wall ulcer were 3.2 and 9.7 %, respectively. The herd had endemic digital dermatitis with prevalence in the adult herd of over 34.2 %. All the ‘non-healing’ claw disorders observed in this study were particularly severe, penetrating the horn and involving the corium. In most of cases the fissure was filled with granulated tissue. In 5 (9.6 %), 6 (11.5 %), 6 (11.5 %) and 2 (3.8 %) of all cattle the claw lesions did not heal after 2, 3, 4 and 6 months, respecitively. In 8 (15.3 %) lesions the exposed corium was never covered by new horn during the 8 month. Microscopically, there was extremely proliferative epidermis, 2-3 times as high as in the controls with severe acanthosis and rete ridge formation. Stratum corneum was hyperplastic. The evidences of healing as reduce of inflammatory reactions in dermis and repair of epidermis were observed at least after 4 weeks in early lesions. Atypical digital dermatitis must be considered an emergency.

An Unexpected Anticholinergic Effect due to Yarrow (Achillea millefolium)

Yarrow (Achillea millefolium) is a widely used plant in folk medicine due to its anti-inflammatory, anti-ulcer and estrogen-related effects. Some side effects including dermal allergic reactions have been reported owing to this herbal remedy. However, the literature about Achillea species do not include any side effects indicating anticholinergic toxicity. A 43-year-old female patient presented to the emergency department with blurred vision, dryness in the mouth, facial flushing and palpitation. She did not have any systemic illnesses and she denied taking any other herbal drugs or medications except yarrow tea (five cups a day, for one week), which she used for the treatment of menometrorrhagia. The constituents of the Achillea species identified in the former studies are highly bioactive, but their effects are not entirely known. Although the Achillea species have been considered as safe medicinal plants, the various pharmacological effects of Achillea species should be cautiously handled