Urticarial Lesions Research Articles

Jellyfish envenomation in an ocean swimmer

A healthy 28-year-old man presented to the Emergency Department (ED) one hour after the sudden onset of sharp, right-sided leg pain that occurred while swimming in the North Atlantic Ocean. He also reported shooting pains radiating toward the groin, worsened by weight-bearing and walking. On examination, he was afebrile with a mild tachycardia and hypertension. Several curvilinear, urticarial lesions, surrounded by a 3 cm by 15 cm region of erythema, were seen on the right lower extremity (Fig. 1). The clinical picture was consistent with a jellyfish sting. Cnidariae, which include jellyfish, possess specialized stinging apparatus called nematocysts, which are concentrated on the tentacles, and which rapidly deliver venom. Cnidarian envenomation should be suspected and treated in patients with painful pruritus after sea-bathing, even if the organism is not directly observed. When left untreated, jellyfish stings may result in scarring, anaphylaxis, or even death in some cases due to a syndrome of systemic pain, hypertension, cardiotoxicity, and pulmonary edema [1]. Species with the most potent venoms largely inhabit IndoPacific waters, but this potentially fatal reaction has been reported on the US coast [2]. Current evidence supports treating jellyfish stings by mechanically scraping the lesions to remove embedded nematocysts, and irrigating the area involved with hot water to deactivate heat-labile venoms [3, 4]. Acetic acid is thought to inactivate the nematocysts of diverse species, and to inhibit the discharge of venom, but its clinical effectiveness has been contested [5]. Because most jellyfish envenomation cases occur in remote locations, emergency personnel should recognize local marine fauna, and direct empiric treatment to these species after suspected stings. The patient did not recall seeing the organism. Scrapings of the wound contained numerous visible nematocysts. The wound was irrigated with an 8 % acetic acid solution, and a topical steroid was applied for symptomatic relief. At 10-day follow-up, the lesions had resolved with moderate post-inflammatory hyperpigmentation, and the radiating pain had subsided.

Real‐time, non‐invasive microscopic confirmation of clinical diagnosis of bullous pemphigoid using in vivo reflectance confocal microscopy

Bullous pemphigoid is an autoimmune disease affecting prevalently the elder. In vivo reflectance confocal microscopy is a non-invasive technique for real-time imaging of the skin with cellular-level resolution. No previous data has been reported about confocal microscopy of bullous pemphigoid. Aim of this preliminary study is the evaluation of the potential of in vivo reflectance confocal microscopy for real-time, microscopical confirmation of clinical bullous pemphigoid diagnosis. A total of nine lesions from patients affected by pemphigoid underwent in vivo reflectance confocal microscopy before histological examination. In our preliminary study, confocal microscopy showed high grade of correspondence to histopathology. In particular, presence of sub-epidermal cleft and variable amount of oedema of the upper dermis associated with inflammatory cells infiltration were seen as prevalent confocal features in the bullous lesions considered. Differently, in urticarial lesions, no specific features could be appreciated at confocal analysis beside the presence of signs of spongiosis and perivascular inflammation. Confocal microscopy seems to be useful for in vivo, microscopical confirmation of the clinical suspect of bullous pemphigoid and for biopsy site selection in urticarial lesions to obtain a more significant specimen for histopathological examination.

Bullous Pemphigoid as Pruritus in the Elderly

In the literature, patients with bullous pemphigoid have been reported to have itch without blisters. Clinical observations in these patients have varied from eczematous or urticarial to papular or nodular skin lesions. Here we investigated the spectrum of clinical variants. Fifteen patients with itch without blisters had immunopathologic findings of bullous pemphigoid. Mean age at diagnosis was 81.7 years. No blistering occurred during the mean 2.2 years of follow-up. Mean delay of diagnosis was 2.8 years. Clinical symptoms were heterogeneous: pruritus sine materia (no primary skin lesions), eczematous, urticarial, papular, and/or nodular skin lesions were seen. Treatment with potent topical corticosteroids or methotrexate sodium led to remission in 11 patients. Itch without skin lesions can be the only symptom of bullous pemphigoid. Therefore, it is important to include serologic and direct immunofluorescence in the diagnostic algorithm of itch. We propose the unifying term pruritic nonbullous pemphigoid for all patients with immunopathologic findings of bullous pemphigoid, itch, and no blisters.

Autoimmunity-Related Neutrophilic Dermatosis

Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

Urticarial Vasculitis: A Retrospective Study of 15 Cases

IntroductionUrticarial vasculitis is a subtype of vasculitis characterized clinically by urticarial lesions and histologically by necrotizing vasculitis. ObjectiveTo study the clinical and histologic features of urticarial vasculitis in patients seen in the dermatology department of Hospital Universitario Virgen de Rocío in Seville, Spain, and to examine the association between hypocomplementemia and systemic disease. Material and methodsWe performed a chart review of histologically confirmed cases of urticarial vasculitis in the database of our department covering a period of 10 years. ResultsFifteen patients (9 women and 6 men with a median age of 51 years) were included. In 14 patients (93%), the lesions persisted for more than 24hours, and in 9 cases (60%) the lesions resolved leaving residual purpura or hyperpigmentation. Seven patients (47%) had low complement levels in the blood, 12 (80%) had extracutaneous symptoms, and 8 (53%) had associated systemic disease, the most common of which was systemic lupus erythematosus. ConclusionsUrticarial vasculitis may be underdiagnosed. Response to treatment is variable, and hypocomplementemia and extracutaneous symptoms may indicate the presence of associated systemic disease.

Retrospective chart review in a cohort of patients with urticarial dermatitis

Urticarial dermatitis is a poorly understood skin condition while it seems to be much more common than the paucity of reports suggest. It manifests with severely pruritic papules and plaques that resemble eczematous and urticarial lesions morphologically. The key clues to diagnosis are the urticarial appearance and overlap with an eczematous reaction. Here, we present a series of 19 cases (13 women and six men) with urticarial dermatitis clinically and histologically. The patients' average age was 58 and most of the cases were idiopathic. Trunk and proximal extremities were the most common sites involved followed by the distal extremities. Poor response to potent topical corticosteroids and antihistamines was usual and many patients required oral prednisone or other immunosuppressant agents or phototherapy.

AB0755 Urticarial vasculitis: A clinical and histopathologic review

BackgroundUrticarial vasculitis is an infrecuent subset of vasculitis described by McDuffy et al, in 1973, characterized clinically by urticarial skin lesions of more than 24 hours duration and histologically by...

Sudden bilateral sensorineural hearing loss associated with urticarial vasculitis

Bilateral sensorineural hearing loss associated with recurrent urticarial skin lesions may be signs of underlying Muckle-Wells syndrome. Previous reports have described the hearing loss to be progressive in nature. To our knowledge, this paper presents the first published case of sudden onset, bilateral sensorineural hearing loss associated with urticarial vasculitis due to underlying Muckle-Wells syndrome. The patient underwent a cochlear implantation with a modest outcome. Cochlear implantation may help to rehabilitate sudden hearing loss associated with this condition, but early diagnosis may allow treatment with interleukin-1β inhibitors such as anakinra.

Urticaria vasculitis: estudio retrospectivo de 15 casos

IntroductionUrticarial vasculitis is a subtype of vasculitis characterized clinically by urticarial lesions and histologically by necrotizing vasculitis. ObjectiveTo study the clinical and histologic features of urticarial vasculitis in patients seen in the dermatology department of Hospital Universitario Virgen de Rocío in Seville, Spain, and to examine the association between hypocomplementemia and systemic disease. Material and methodsWe performed a chart review of histologically confirmed cases of urticarial vasculitis in the database of our department covering a period of 10 years. ResultsFifteen patients (9 women and 6 men with a median age of 51 years) were included. In 14 patients (93%), the lesions persisted for more than 24hours, and in 9 cases (60%) the lesions resolved leaving residual purpura or hyperpigmentation. Seven patients (47%) had low complement levels in the blood, 12 (80%) had extracutaneous symptoms, and 8 (53%) had associated systemic disease, the most common of which was systemic lupus erythematosus. ConclusionsUrticarial vasculitis may be underdiagnosed. Response to treatment is variable, and hypocomplementemia and extracutaneous symptoms may indicate the presence of associated systemic disease.

Practical guidelines for the use of steroid-sparing agents in the treatment of chronic pruritus

Chronic pruritus in the adult patient is both an underappreciated and a difficult to treat condition. In the vast majority of cases, itch is the result of inflammatory skin disease and therefore may be responsive to systemic anti-inflammatory therapies. Urticarial dermatitis is an under-recognized cause of chronic itch in the adult population. Patients with this disorder are characterized by prolonged, prednisone-responsive pruritus, often in the absence of substantial cutaneous findings. Skin findings, when present, can range from subtle, persistent urticarial lesions to excoriated papules, often intermixed with urticaria, eczematous change, and lichenification secondary to chronic scratching. Hereby, we describe our algorithm for evaluation and management of adult patients with refractory pruritus (urticarial dermatitis in particular), including evaluation for other etiologies of pruritus, pre-immunosuppression workup, and the use of azathioprine and other steroid-sparing agents for treatment of recalcitrant itch.

Decrease in Fc Epsilon R1 Antibodies with IVIG

RationaleChronic idiopathic urticaria (CIU) can be extremely difficult to treat. Several reports show efficacy with intravenous immunoglobulin (IVIG). But there have been no records of Fc Epsilon R1 (FceR1) antibodies in these. I present a case where such measurement had been done, suggesting a possible mechanistic connection.MethodsA case of refractory CIU treated with IVIG is presented.ResultsA 52 year-old female with a history of hypothyroidism, chronic sinusitis, and asthma presented initially with 1 week of recurrent urticarial lesions. Over the next several months, her symptoms went on to include angioedema of the lips. Initial labs, including complete blood count with differential, blood chemistries, liver function testing, C3, C4, and thyroid stimulating hormone level were normal. Over 4 months, several antihistamines, colchicine, doxepin, dapsone, and montelukast offered no relief. Multiple oral steroid courses also failed. She had an FceR1 antibody level drawn, which was 22.1 units. Azathioprine and cyclosporine were then each tried with minimal benefit. She underwent a humoral immunodeficiency survey due to repeated sinus infections and was diagnosed with specific antibody deficiency. She was started on IVIG. After 2 doses of IVIG, she had no hives or edema. She stopped all her urticarial-related medication except cyclosporine and had no recurrence. Her FceR1 antibody level was repeated, and it had dropped to 2.65 units.ConclusionsIVIG may reduce the symptoms of urticaria and angioedema in CIU by decreasing Fc Episilon R1 antibodies. Further studies are needed to further investigate this. RationaleChronic idiopathic urticaria (CIU) can be extremely difficult to treat. Several reports show efficacy with intravenous immunoglobulin (IVIG). But there have been no records of Fc Epsilon R1 (FceR1) antibodies in these. I present a case where such measurement had been done, suggesting a possible mechanistic connection. Chronic idiopathic urticaria (CIU) can be extremely difficult to treat. Several reports show efficacy with intravenous immunoglobulin (IVIG). But there have been no records of Fc Epsilon R1 (FceR1) antibodies in these. I present a case where such measurement had been done, suggesting a possible mechanistic connection. MethodsA case of refractory CIU treated with IVIG is presented. A case of refractory CIU treated with IVIG is presented. ResultsA 52 year-old female with a history of hypothyroidism, chronic sinusitis, and asthma presented initially with 1 week of recurrent urticarial lesions. Over the next several months, her symptoms went on to include angioedema of the lips. Initial labs, including complete blood count with differential, blood chemistries, liver function testing, C3, C4, and thyroid stimulating hormone level were normal. Over 4 months, several antihistamines, colchicine, doxepin, dapsone, and montelukast offered no relief. Multiple oral steroid courses also failed. She had an FceR1 antibody level drawn, which was 22.1 units. Azathioprine and cyclosporine were then each tried with minimal benefit. She underwent a humoral immunodeficiency survey due to repeated sinus infections and was diagnosed with specific antibody deficiency. She was started on IVIG. After 2 doses of IVIG, she had no hives or edema. She stopped all her urticarial-related medication except cyclosporine and had no recurrence. Her FceR1 antibody level was repeated, and it had dropped to 2.65 units. A 52 year-old female with a history of hypothyroidism, chronic sinusitis, and asthma presented initially with 1 week of recurrent urticarial lesions. Over the next several months, her symptoms went on to include angioedema of the lips. Initial labs, including complete blood count with differential, blood chemistries, liver function testing, C3, C4, and thyroid stimulating hormone level were normal. Over 4 months, several antihistamines, colchicine, doxepin, dapsone, and montelukast offered no relief. Multiple oral steroid courses also failed. She had an FceR1 antibody level drawn, which was 22.1 units. Azathioprine and cyclosporine were then each tried with minimal benefit. She underwent a humoral immunodeficiency survey due to repeated sinus infections and was diagnosed with specific antibody deficiency. She was started on IVIG. After 2 doses of IVIG, she had no hives or edema. She stopped all her urticarial-related medication except cyclosporine and had no recurrence. Her FceR1 antibody level was repeated, and it had dropped to 2.65 units. ConclusionsIVIG may reduce the symptoms of urticaria and angioedema in CIU by decreasing Fc Episilon R1 antibodies. Further studies are needed to further investigate this. IVIG may reduce the symptoms of urticaria and angioedema in CIU by decreasing Fc Episilon R1 antibodies. Further studies are needed to further investigate this.

A study on Paederus dermatitis outbreak in a suburban teaching research hospital, Kanchipuram, India.

Paederus dermatitis, a kind of irritant contact dermatitis by Staphylinid beetle, is more prevalent in Asia-Pacific countries with the attributes of tropical climate. Brushing, pressing, or crushing of the beetle against the skin releases the pederin toxin (pederin) that can produce urticarial, vesicular, and bullous lesions. We conducted a 1-year retrospective study of 84 patients with Paederus dermatitis attending our hospital to study the clinical patterns of dermatitis and epidemiological prevalence. It mostly affects the hostel students residing within the campus near the paddy fields. Itching was most common symptom, involving mainly the neck and arms. Linear erythematous lesions were the common sign involving the extremities (40.1%), neck (36.4%) and trunk (32.1%). Vesicles and pustule formation was seen in (51.19%) of the patients, respectively. The most striking feature of Paederus dermatitis, the ˜Kissing lesions were seen in (2.4%) of the patients. Periorbital involvement was seen in (17.4%) of the cases. Paederus beetles were frequently seen in the campus attracted by incandescent and fluorescent lights. Simple preventive measures such as use of insecticide like pyrethroid, clearing of excess vegetation would check the Paederus infection. Clinical education and awareness regarding this condition will prevent misdiagnosis.

Chronic urticaria and angioedema associated with Hashimoto’s thyroiditis in a child: A case report

The association between chronic urticaria and Hashimoto’s thyroiditis has been rarely reported in children. Case Report: We are reporting a case of an eight-year-old girl with chronic urticaria unresponsive to antihistaminic therapy, who was subsequently diagnosed to have Hashimoto’s thyroiditis. Patient’s urticarial lesion remitted after treatment with levothyroxine. Conclusion: We emphasize to consider testing for Hashimoto’s thyroiditis by thyroid autoantibodies and thyroid profile in cases of chronic urticaria, and starting the patient on levothyroxine for the symptomatic improvement of both chronic urticaria and Hashimoto’s thyroiditis.

Follicular traction urticaria

To the Editor: A 32-year-old nonatopic Turkish woman presented with a 7-month history of pruritic wheals of 1 to 3 mm developing within 10 to 15 minutes every time she waxed or used an electrical epilator on her legs. The reaction spontaneously resolved within 2 to 3 hours. Although shaving or depilatory creams did not provoke lesions, plucking eyebrows by tweezers induced localized lesions. No spontaneous attacks of urticaria were reported. There was no history of any drug intake. No urticarial lesions could be elicited by stroking the patient's forearm, leg, and back with a blunt object. Skin traction or gentle hair traction did not provoke lesions whereas hair removal test with the electrical epilator on one leg led to reddish, exclusively follicular urticarial papules within 10 minutes (Fig 1). The papules showed some coalescence at 30 minutes (Fig 2), and the reaction resolved completely within 3 hours. Skin biopsy findings were consistent with urticaria. The other leg was epilated with a depilatory cream. Using the electrical epilator on the hairless control leg caused no reaction. Fig 2Follicular traction urticaria. A, Close-up to follicular urticarial papules at 10 minutes of hair removal test. B, Follicular urticarial papules showing some coalescence at 30 minutes of hair removal test. View Large Image Figure Viewer Download Hi-res image

Immediate and Delayed Hypersensitivity to Systemic Corticosteroids

Both immediate, type I reactions and delayed hypersensitivity, type IV reactions to systemic corticosteroid preparations have been reported. Type I reactions are rare, with delayed hypersensitivity reactions being slightly more common. A 33-year-old woman presented repeatedly to the emergency department with asthma attacks. She developed pruritus and hives approximately 30 minutes after the administration of parenteral corticosteroids. Her respiratory status deteriorated approximately 6 hours after she received the corticosteroids. An acute eczematous dermatitis on her face, neck, and upper body appeared 24 hours after administration of the corticosteroids. The dermatitis peaked at 72 hours. Intradermal testing to Solu-Medrol, Solu-Cortef, prednisone, and Decadron confirmed a type I, anaphylactoid reaction. The dermatitis that presented 24 hours after administration of the parenteral corticosteroids is consistent clinically with a type IV delayed hypersensitivity reaction to the corticosteroids. A second patient, a 51-year-old woman, developed urticarial lesions that lasted approximately 30 minutes, immediately after intralesional triamcinolone injections for keloid scars. Intradermal testing was performed. She showed a positive reaction to triamcinolone confirming a type I allergy to this steroid. It is important to consider an allergy to corticosteroids in patients with worsening anaphylactic symptoms after administration of systemic corticosteroids.

Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials. The primary aims of the study were: (i) to characterize the clinical features of BP at time of diagnosis; and (ii) to assess the diagnostic delay in BP and its impact on prognosis All new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were prospectively registered by means of a standardized data collection form. One hundred-seventeen patients with BP were included in the study. 97cases (82.9%) had typical features with vesicles, blisters and/or erosions at time of diagnosis, while in the remaining cases (17.1%) only excoriations, eczematous and/or urticarial infiltrated lesions were observed. Head/neck as well as palmo-plantar involvement were found in up to 20% of patients, while mucosal lesions were present in 14.5% of the cases. Diagnosis was made after a mean of 6.1 months after the first symptoms. In patients, in whom the diagnostic delay was 4 months or more (defined as late diagnosis group), lesions were more often limited to one body area. The type of lesions did not affect the diagnostic delay. Diagnosis was made more rapidly in patients with limb involvement compared to those without. The calculated mortality rate in the early and late diagnosis group was 18.9% and 17.9%, respectively, without significant difference. BP often presents with bullous lesions at time of diagnosis after a mean diagnostic delay of 6 months. Nevertheless, up to 20% of patients lack obvious blistering and postbullous erosions, mimicking thus a variety of inflammatory dermatoses. Localized disease is associated with an increased diagnostic delay, which has however no impact on prognosis.

A Rare Case of Small Bowel Angioedema with Normal C4 Level

Introduction: Angioedema is self-limited, localized subcutaneous (or submucosal) swelling, which results from extravagation of fluid into interstitial tissues. Angioedema may occur in isolation, accompanied by urticaria, or as a component of anaphylaxis. We describe a case of isolated angioedema of the bowel, a rare presentation, occurring in a man with normal C4 and C1q level. Case Description: A 23-year-old male with H/O no medical problems was admitted to our hospital for nausea, vomiting and abdominal pain for one day duration. He ate a large omelet for breakfast and few hours later developed urticaria, nausea and severe heartburn. He went to the nearest ER, where he was discharged on Benadryl and proton pump inhibitors. In the evening his symptoms progressed and nausea/vomiting worsened. He also had a colicky abdominal pain and diarrhea. The recent allergic triggers like tattoos, soaps, new foods, parenteral injections, detergents, medications like angiotensin-converting enzyme inhibitors, could not be identified. Family history was significant for allergic reaction in his father that caused him to break out in hives. Examination shows multiple urticarial lesions on both arms and shoulders. Lips are swollen and abdomen is soft with epigastric tenderness. CT scan of abdomen shows mild enteritis with mildly distended small bowel. Patient did not improve to initial conservative treatment consisting of nasogastric tube and antiemetics, but improved markedly with the steroid treatment. The patient work up including C4 level; C1 inhibitor antigenic level; C1q level was negative. Discussion: Angioedema affecting the bowel wall presents as colicky abdominal pain, sometimes accompanied by nausea, vomiting and/or diarrhea. Bowel wall edema can often be visualized by abdominal CT. It is seen in patients on ACE inhibitors and in those with hereditary or acquired C1 inhibitor deficiency. The particular case was unique because of normal C4 and C1 inhibitor antigenic level. The patient improved on antihistamines and steroids. High degree of suspicion for bowel wall angioedema is needed in a patient presenting with urticaria, severe nausea and vomiting, who is not improving with conservative treatment.

Neutrophilic Urticaria or Urticaria With Predominantly Neutrophilic Inflammatory Infiltrate: Study of Its Clinical and Histopathologic Characteristics and Its Possible Association With Rheumatic Disease

IntroductionNeutrophilic urticaria, described by Winkelmann in 1985, has yet to be completely defined and its clinical significance is poorly understood. Nevertheless, recent publications suggest that it could be a marker for rheumatic disease. The primary objective of this study was to compare the prevalence of rheumatic disease in 2 groups of patients with urticaria: those with conventional urticaria (non-neutrophilic inflammatory infiltrate) and those with neutrophilic urticaria. Material and methodsWe retrospectively reviewed all biopsy samples taken from urticarial lesions in our hospital between January 1, 1999 and June 28, 2009. Urticaria was classified according to predefined morphologic and histopathologic patterns. We compared the clinical and histologic characteristics of neutrophilic urticaria with those of conventional urticarias in the 84 patients included. ResultsOf the 84 patients, 57.1% had neutrophilic urticaria. We did not find significant differences between the percentages of patients with rheumatic disease between the neutrophilic and nonneutrophilic urticaria groups. In patients with acute urticaria, we found a significantly higher proportion of samples with histopathologic signs of neutrophilic urticaria as opposed to conventional histopathology. Patients with neutrophilic urticaria also had higher white blood cell counts. ConclusionsThe percentage of samples with neutrophilic urticaria in this series (57.1%) is higher than the percentages reported in the literature, possibly because we tended to biopsy recent lesions. We highlight that the presence of neutrophils in the biopsies of urticaria is a common finding and does not appear to be associated with other diseases.

Reticular variant of mid‐dermal elastolysis accompanied by persistent urticarial lesions

Reticular variant of mid‐dermal elastolysis accompanied by persistent urticarial lesions

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria

Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using single stains for antitryptase and anti-FXIIIa antibodies, as well as double immunogold labeling for both. Some sections showed mast cells in the process of degranulation. Following double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were found together throughout the granules in mast cells, indicating that tryptase and FXIIIa are located inside each one of the granules of these cells. Interestingly, we found strong evidence of the presence of tryptase and factor XIIIa in the superficial skin nerves of these patients, both in cases of urticarial lesions (wheals) and in the apparently normal skin. Tryptase and FXIIIa are present in the superficial nerves of the skin in drug-induced acute urticaria. This is the first report of tryptase and FXIIIa expression in the superficial skin nerves of patients with urticaria. Tryptase may be participating in neural activation in these patients, while FXIIIa may be present in the nerves to guarantee the functional integrity of structures.