Suction blister device with regulation of temperature: Demonstration of histamine release and temperature change in cold urticaria

Summary A suction blister device with a sensitive thermometer and with a temperature regulator was constructed. Utilizing this device, it was demonstrated that the cold challenge induces an increase in the skin temperature in cold urticaria patients during the cold challenge and a simultaneous release of histamine into the suction blisters. The skin temperature increases faster after the cold challenge period in cold urticaria patients than in normal control persons. This could be explained by vasodilatation and increased circulation in the skin, following the release of histamine in the cold urticaria reaction.     

咪唑斯汀治疗原发性获得性寒冷性荨麻疹临床疗效观察

目的：评价咪唑斯汀治疗原发性获得性寒冷性荨麻疹的疗效与安全性。方法：采用多中心、随机双盲、安慰剂平行对照的方法，将入选患者随机分为试验组和对照组，分别接受咪唑斯汀和安慰剂治疗，观察患者对冷刺激试验的风团反应和瘙痒程度，以及临床反应。结果：试验组患者冷刺激试验的风团反应、冷刺激试验复温20min时的瘙痒程度、遇冷空气或冷水后出现风团或瘙痒的程度与安慰剂组相比有统计学差异（P〈0．05）。结论：咪唑斯汀治疗原发性获得性寒冷性荨麻疹安全、有效。     

Diagnosis of Raynaud's phenomenon by thermography

Background/aims: The aim was to clarify whether cold fingers before a moderate cold stress test can predict a prolonged delay (more than 20 min) in rewarming, as diagnostic for Raynaud's phenomenon.
Methods: A retrospective study was conducted on 71 patients suspected of suffering from Raynaud's phenomenon. The thermal gradient from the metacarpophalangeal joints to the finger tips was calculated for each finger and cold fingers were defined by a temperature difference of more than −0.5°2C.
Results: Combining the frequencies of cold fingers with a diagnosis Raynaud's phenomenon resulted in a sensitivity of 78.4%, a specificity of 72.4% and diagnostic accuracy of 74.0%.
Conclusion: Based on a positive predictive value of 58.5%, it was concluded, that a prolonged delay of rewarming after a cold stress test cannot be predicted sufficiently by the presence of cold fingers alone, and that a cold stress test is necessary to confirm the diagnosis objectively.     

Results of the treatment in cases of cold urticaria, cold pruritus and cold rhinitis with peritol (zyproheptadinhydrochlorid) (author's transl)]

19 patients with cold urticaria, 5 with cold pruritus and 2 with cold rhinitis were successfully treated with peritol with the exception of one patient who suffered from a symptomatic pruritus due to polycythemia vera. Even in cases of recurrence the treatment was at once successful. Therefore peritol seems to be useful in the treatment of diseases due to cold.     

Alpha-fluoromethylhistidine in the treatment of idiopathic cold urticaria

Summary Alpha-fluoromethylhistidine (alpha-FMH), a new irreversible inhibitor of mammalian histidine decarboxylase, was tested in the treatment of idiopathic cold urticaria in 11 patients. In the initial trial with 50 mg b.i.d., a significant decrease (about 30%) in the total blood histamine level was found after 3 weeks of treatment but clinically there was no improvement in the symptoms of ten cold urticaria patients nor in the responses to the ice-cube test. In the second trial with three patients suffering from severe idiopathic cold urticaria, a higher dose of up to 500 mg b.i.d. of alpha-FMH for 3 weeks resulted in a marked decrease in the total blood histamine level as well as in an apparent inhibition of histamine synthesis in the skin previously exposed several times to cold water. The symptoms of cold urticaria and the responses in the ice-cube tests also decreased simultaneously. No clinical side effects nor changes in laboratory analysis were seen during the treatment with alpha-FMH. These results suggest that alpha-FMH may be useful in the treatment of severe cold urticaria especially in combination with histamine exhaustion of mast cells using cold water.     

Preventive effects of various types of footwear and cleaning methods on dermatophyte adhesion

Tinea pedis is contagious and typically spreads from infected to non-infected persons. The purpose of this study was to evaluate the efficacy of footwear in preventing tinea pedis adhesion. Using the stamp culture method, we investigated the effectiveness of preventing dermatophyte passage by the wearing of stockings made of nylon, socks made of cotton and tabi (Japanese socks), as well as the effect of removing dermatophytes from these items by washing with soap, cold water and cold water after turning inside-out. For sandals, sneakers and boots, we also investigated the effect of dermatophyte removal by pouring cold water into the footwear, wiping with a wet towel, and pouring boiling water into the footwear. The wearing of socks or tabi was effective in preventing passage of dermatophytes. The stocking material proved to be too thin to prevent passage. On the inner side of socks (the side of the sole), all treatments were effective at removing dermatophytes, but on the outer side of socks (the side touching the surface of the sandals), the treatment of washing in cold water after turning inside-out resulted in significantly more dermatophytes as compared with the other treatments. Pouring cold water, wiping with a wet towel and pouring boiling water were all effective for removing dermatophytes from sandals and sneakers. However, for boots, the treatment of pouring cold water was less effective. To prevent the adhesion of dermatophytes to sandals, wearing socks or tabi was effective, and the treatments of washing socks in cold water after turning inside-out and of pouring cold water into the boots were less effective than the others.     

Cold urticaria patients exhibit normal skin levels of functional mast cells and histamine after tolerance induction

Cold urticaria is a skin condition characterized by rapid appearance of itchy wheals and occasionally angioedema in response to cold stimulation. Antihistamines do not sufficiently protect all patients from symptoms, even when used in higher than standard doses. In these patients, desensitization to cold can be beneficial. The aim was to investigate whether desensitization can lower temperature thresholds and reduce release of histamine in the skin. Cold urticaria patients were subjected to desensitization and assessed for skin responses to cold stimulation and codeine before and after. Histamine levels mediated by cold and codeine were determined by cutaneous microdialysis before and after desensitization in patients and healthy controls. Desensitization to cold resulted in protection from cold-induced symptoms and lower temperature thresholds in six out of nine patients. Desensitization also prevented histamine release after skin exposure to cold. Surprisingly, skin histamine levels and release after codeine injection were found to be normal in desensitized patients.     

Clinical scoring and biophysical evaluation of nasolabial skin barrier damage caused by rhinorrhea

Background: An acute viral cold is a very common illness and is characterized by sneezing and a runny nose. Because of rhinorrhea and frequent use of handkerchiefs, the skin around the nose feels uncomfortably dry and flaky. Objectives/Methods: To evaluate the nasolabial skin barrier impairment, 14 female volunteers with a common cold were recruited. Visually assessed clinical scoring and/or biophysical measurements – including transepidermal water loss, stratum corneum hydration, skin colour, squamometry, skin pH, and a skin surface lipid profile analysis – were carried out at the start of the cold, a second time when the severity of the cold symptoms was maximal, and finally when the volunteers felt healthy again and stopped using handkerchiefs. Results and Conclusions: Transepidermal water loss assessments showed significantly higher measurements on the maximum outcome of the nasal cold compared with the time‐point when the symptoms of the cold had disappeared. This was in accordance with skin colour chroma a* measurements and the visually assessed skin erythema and scaliness scores, indicating that the superficial nasolabial skin barrier was inferior at the maximum of a nasal cold in comparison with the skin condition when volunteers were fully recovered.     

Kälteinduzierte Quaddeln und Angioödeme

The onset of wheals and/or angioedema following the exposure to cold may be associated with a number of different diseases. Most frequently this occurs in cold contact urticaria, a type of physical urticaria, which is characterized by a positive cold stimulation test. The clinical symptoms are based on cold-dependent mast cell activation with subsequent release of proinflammatory mediators. In cases of negative or atypical reaction to cold stimulation testing rare acquired atypical or familiar cold urticaria forms may be suspected. Strict avoidance of cold should be recommended as far as possible. As the underlying causes of cold contact urticaria are widely unknown, the symptomatic use of non-sedating antihistamines is the treatment of first choice. The very rare familiar cold auto-inflammatory syndrome (FCAS) is based on CIAS1/NLRP3 mutations and may be treated effectively by neutralization of pathogenic interleukin 1β.     

Localized Cold Urticaria to the Face in a Pediatric Patient: A Case Report and Literature Review

Abstract: We present a curious case of localized cold urticaria restricted to the face in a 10‐year‐old girl. Testing for the condition using an ice cube was positive only in the facial area. After 2 years, the patient continues to experience localized urticaria only on her face on cold exposure. A review of the available published medical literature on cold urticaria was performed using Ovid and PubMed databases. The literature search was not limited to the English language. Only three other cases of cold urticaria localized to the face were identified. Upon review of the published reports on cold urticaria and discussion of classification and diagnostic testing, we conclude that cold urticaria clearly is a rare and poorly understood entity.     

Combination of localized heat urticaria and cold urticaria. Release of histamine in suction blisters and successful treatment of heat urticaria with doxepin

Two female patients with a rare combination of localized heat urticaria and cold urticaria are described. One patient had localized heat urticaria combined with delayed cold urticaria and the other patient had localized heat urticaria in combination with idiopathic (primary acquired) cold urticaria. Increased histamine concentration was measured in suction blister fluid samples collected immediately after the heal challenge in both patients. Doxepin effectively suppressed the whealing response on the heat challenged skin. These results suggest that histamine is the main mediator in heat urticaria reactions.     

Combined cold urticaria and cholinergic urticaria clinical characterization and laboratory findings

Thirteen patients with both cold and cholinergic urticaria are reported. There was considerable variability, particularly in the cold urticaria which was of the common cold contact type in seven patients, of the generalized cold induced cholinergic type in two and in four patients the lesions induced by direct contact with ice were morphologically like cholinergic urticaria, but appeared despite prior application of an acetyl choline antagonist. The natural history, laboratory findings and the effects of therapy are discussed.     

An unusual reaction to cold: a sporadic case of familial polymorphous cold eruption?

A 14-year-old Japanese girl had a lifelong history of skin lesions developing after generalized exposure to cold air; the lesions were often accompanied by systemic symptoms such as fever and chills. The skin lesions were non-pruritic, maculopapular, erythematous eruptions and were neither urticarial nor angioedematous. An ice-cube test was negative. Laboratory examinations showed marked leucocytosis during an acute attack. On the basis of clinical features, histological findings and laboratory data, although these symptoms were sporadic, the most likely diagnosis was familial polymorphous cold eruption, which has also been referred to as familial cold urticaria. Serum levels of granulocyte colony-stimulating factor and interleukin 6 were significantly elevated during an acute attack after cold exposure, suggesting that both cytokines played important parts in the development of her condition.     

Muckle-Wells syndrome: clinical and histological skin findings compatible with cold air urticaria in a large kindred

BACKGROUND: Muckle-Wells syndrome is a rare familial disease with autosomal dominant inheritance, characterized by cold sensitivity and polyarthralgias since childhood, with possible later development of nerve deafness and renal amyloidosis. The nature of the skin manifestations is, however, not well characterized. OBJECTIVES: To clarify the nature of cutaneous cold sensitivity in patients with Muckle-Wells syndrome by studying clinical aspects and histological features. METHODS: Eighteen members of a family with Muckle-Wells syndrome and the recently identified mutation of the CIAS1 gene at locus 260 of chromosome 1q44 were available for study. Examination included a thorough history, physical examination and a battery of laboratory tests. In two brothers, standard cold contact and cold air provocation tests were performed, as were biopsies from normal and lesional skin. RESULTS: All affected family members reported an increased sensitivity to cold, dampness or changes in temperature, and most had arthritis and conjunctivitis. Eight had developed hearing loss, four renal involvement, and amyloid deposits were found in three of five patients in whom rectal biopsies were performed. Laboratory tests showed leucocytosis and elevated C-reactive protein, but no serum cold agglutinins and cryoglobulins. Skin eruptions, with weals of 0.2-3 cm, lasted from 5 to 24 h and were associated with local itching or pain as well as fever, malaise and chills. On cold provocation of two patients, lesions could be reproduced by cold air, but not by contact with an ice cube or cold water. On histology, there was increased vasodilatation, marked infiltration with neutrophils and monocytes/macrophages, and increased expression of beta 2 integrins in lesional vs. normal skin. Numbers of mast cells as well as expression of interleukin-3 and tumour necrosis factor-alpha were unchanged. CONCLUSIONS: Cold-induced skin lesions in Muckle-Wells syndrome represent typical generalized cold air/wind inflammatory reactions, as also observed in familial cold urticaria. Microscopic features are similar to those observed in other types of urticaria.     

TREATMENT OF ACQUIRED COLD URTICARIA WITH AZATADINE

Acquired cold urticaria is a clinical entity in which wheals appear on exposure to cold, rive patients with cold urticaria were treated with 0,1 mg of azatadine four times a day. Followed for 15–36 months (mean 22 months), the patients were under good control. No significant side effects were noted. Drowsiness was initial and transitory. Ice cube test was positive in four and negative in one patient. This preliminary study suggests that azatadine may be a useful drug in treatment of cold urticaria.     

Sequential application of cold and sodium lauryl sulphate decreases irritation and barrier disruption in vivo in humans

BACKGROUND: Irritant contact dermatitis (ICD) is one of the most frequent types of occupational dermatitis. Different factors are involved in the development of contact dermatitis. In the food-processing industry, the combined exposure to different irritants may be involved in the development of ICD. Few data have been published regarding the irritant potential of sodium lauryl sulphate (SLS) in combination with cold. OBJECTIVES: The present study was intended to analyse whether cold exposure and low skin temperature influence the development of ICD. METHODS: Twenty (part I) and 12 (part II) healthy volunteers were exposed twice daily for 4 days to SLS alone, different low temperatures alone (4 degrees C six times for 90 s with an interval of 20 s or 15 degrees C for 10 min) or a combination of cold and SLS (19.6 microL SLS 1% cm(-2), part I; or 52.6 microL SLS 0.5% cm(-2), part II) using the tandem repetitive irritation test. Irritant cutaneous reactions were measured by noninvasive biophysical methods with transepidermal water loss as a parameter for permeability barrier function and skin colour reflectance together with visual scoring as parameters for inflammatory reactions. RESULTS: Cold alone caused no significant skin reaction compared with untreated control. Exposure to SLS alone and SLS together with cold (independent of the applied temperature of 4 or 15 degrees C) twice daily induced a clear irritant reaction and barrier disturbance. Reactions did not differ whether SLS was applied before or after cold. Furthermore, 'tandem application' of cold and SLS diminished the barrier disruption and irritant reaction compared with SLS alone. CONCLUSIONS: We conclude that the application of cold may have a protective effect on the development of ICD, at least in our short-term model.     

Cold urticaria. Clinical findings in 220 patients

Patients with cold urticaria, a total of 220, were studied in Finland. Sixty-three percent of the patients were female. The diagnosis was based on a positive ice cube test in 90% of cases, and the other cold tests were needed to certify the diagnosis for the remainder of patients. The mean age at the onset of the disease was 25.1 years (range, 1-74), and the mean duration of symptoms was 6.3 years (range, 3 weeks to 37 years). Cold urticaria symptoms had disappeared in fifty-three patients (24%), but there was a recurrence of the disease in twelve. Idiopathic (primary acquired) cold urticaria was present in 96% of the patients. Only two patients had a secondary acquired cold urticaria. Two patients had cold-induced, "cholinergic" urticaria, and four patients had a delayed type of cold urticaria. Twenty-one percent of the patients had dermatographism, 8% had cholinergic urticaria, and two patients (1%) had heat urticaria concurrently with cold urticaria.     

Emollients and the response of facial skin to a cold environment

BACKGROUND: It is debated whether the use of emollients, in cold weather, constitutes a protective factor or a risk factor for frostbite. OBJECTIVES: To compare the effects of two emollients [oil in water (O/W) and petrolatum] on facial skin in response to cold exposure. METHODS: Fifteen volunteers participated in the experiment, consisting of 60 min in a cold room (-5 degrees C), preceded and followed by 30 min of acclimatization at room temperature. In the cold room, O/W was applied on one cheek and petrolatum on the other. The cheeks were exposed to wind, produced by a fan, to cool further the skin by the wind chill index. Skin temperature, redness, and transepidermal water loss (TEWL) were measured on both cheeks. RESULTS: Facial skin treated with O/W was significantly colder (up to 1.3 degrees C) than facial skin treated with petrolatum, but the difference disappeared within 20 min. Agreement between temperature measurements and subjective thermal sensations was poor (Cohen's kappa = -0.13). At no point did the paired skin redness and the paired TEWL values vary significantly. The TEWL levels were significantly lower 30 min after the cold exposure than before, but had reached pre-exposure levels the following day. CONCLUSIONS: This study demonstrates that for a duration exposure of 20 min, facial skin treated with O/W achieves a lower temperature than facial skin treated with petrolatum. The two emollients had in all other aspects the same effect on the response of facial skin to cold.     

Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo.

Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P less than .01). The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria, while placebo and chlorpheniramine proved ineffective.