Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial.

BACKGROUND: Pregabalin may reduce postoperative pain and opioid use. Higher doses may be more effective, but may cause sedation and confusion. This prospective, randomized, blinded, placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty, but increases drowsiness and confusion. METHODS: Patients (30 per group) received capsules containing pregabalin (0, 50, 100, or 150 mg); two capsules before surgery, one capsule twice a day until postoperative day (POD) 14, one on POD15, and one on POD16. Multimodal analgesia included femoral nerve block, epidural analgesia, oxycodone-paracetamol, and meloxicam. The primary outcome was pain with flexion (POD14). RESULTS: Pregabalin did not reduce pain at rest, with ambulation, or with flexion at 2 weeks (P=0.69, 0.23, and 0.90, respectively). Pregabalin increased POD1 drowsiness (34.5, 37.9, 55.2, and 58.6% in the 0, 50, 100, and 150 mg arms, respectively; P=0.030), but did not increase confusion (0, 3.5, 0, and 3.5%, respectively; P=0.75). Pregabalin had no effect on acute or chronic pain, opioid consumption, or analgesic side-effects. Pregabalin reduced POD14 patient satisfaction [1-10 scale, median (first quartile, third quartile): 9 (8, 10), 8 (7, 10), 8 (5, 9), and 8 (6, 9.3), respectively; P=0.023). Protocol compliance was 63% by POD14 (50.0, 70.0, 76.7, and 56.7% compliance, respectively), with no effect of dose on compliance. Per-protocol analysis of compliant patients showed no effect of pregabalin on pain scores. CONCLUSIONS: Pregabalin had no beneficial effects, but increased sedation and decreased patient satisfaction. This study does not support routine perioperative pregabalin for total knee arthroplasty patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/study/NCT01333956.

Variation in allergen content over time of acrylates/methacrylates in patch test preparations.

BACKGROUND: Acrylates/methacrylates are volatile substances. There might be a gradual decrease in acrylate/methacrylate allergen content over time in patch test preparations but this has not yet been documented. OBJECTIVES: To determine the allergen content of acrylates/methacrylates in patch test preparations over time under different storage conditions. METHODS: Five acrylate/methacrylate allergens [2-hydroxyethyl methacrylate (2-HEMA), methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), triethylene glycol diacrylate (TREGDA) and 2-hydroxypropyl acrylate (2-HPA)] in syringes and IQ™ chambers (Chemotechnique Diagnostics, Vellinge, Sweden) were analysed using gel permeation chromatography and high-performance liquid chromatography to measure the allergen content over time in samples stored in the freezer, refrigerator and under room temperature. RESULTS: The concentration of allergens in syringes decreased with time. Those stored at room temperature had the fastest rate of decrease, followed by those in the refrigerator and freezer. In most cases, in syringes or IQ™ chambers under all storage conditions, the MMA decreased most rapidly, followed by 2-HPA, 2-HEMA, EGDMA and TREGDA. The allergens in the IQ™ chambers rapidly disappeared, with almost all samples reaching nondetectable levels by day 8. MMA was the first to reach a nondetectable level--at day 2. CONCLUSIONS: Acrylate/methacrylate allergens are lost rapidly from IQ™ chambers especially if stored at room temperature. Allergens in syringes remain above 80% of their initial concentrations for longer periods compared with IQ™ chambers. In syringes and IQ™ chambers there is a slower rate of decrease in concentration when the storage temperature is lower. Allergens should be stored refrigerated, replaced regularly, and freshly applied on to test patches on the day of use.

A randomized double-blind controlled trial to compare a triclosan-containing emollient with vehicle for the treatment of atopic dermatitis.

The use of topical antiseptics in the treatment of atopic dermatitis (AD) has previously been explored. However, no triclosan-containing leave-on emollient has been evaluated previously, to our knowledge. The aims of this study were to assess the safety and efficacy of an emollient containing triclosan compared with the emollient alone (vehicle) for the treatment of AD. Eligible patients with mild to moderate AD were randomized to receive either the study cream or vehicle. All patients also received a low-potency corticosteroid cream to use during the treatment phase of the study if necessary. Patients were assessed for severity according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of corticosteroid used, patient assessment of cream, and adverse events (AEs). In total, 60 patients received either the study cream or vehicle, and an intention-to-treat analysis was performed. At day 14, there was a significant decrease in SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day 27, although there was an improved mean reduction from baseline, this was no longer significant (P > 0.05). Only four patients had mild treatment-related AEs. The mean total amount of topical steroid applied by the patients using the study was significantly lower than that used by controls (P = 0.40). Triclosan-containing leave-on emollient was safe and highly acceptable to patients. However, the overall benefit on day 27 was not significant. Nevertheless, the amount of topical steroid used by patients was significantly less with the study cream than with the vehicle, thus further studies are needed to confirm its steroid-sparing effect.

Atopy patch testing with aeroallergens in patients with atopic dermatitis and controls in Singapore.

The role of allergy in atopic dermatitis is controversial. The atopy patch test (APT) has been used to investigate the association between atopic dermatitis and aeroallergen allergy. To determine the proportion of patients with atopic dermatitis with positive patch tests to common local aeroallergens and to compare this to controls with and without respiratory atopy, we performed APT, skin-prick tests (SPT) and IgE radioallergosorbent tests (RAST) on 73 patients with atopic dermatitis and on 38 nonatopic controls (13 with and 25 without respiratory atopy). The allergens used were house dust mite, cat dander, Bermuda grass and German cockroach. Only the APT for house dust mite showed a significant difference between the two groups. APT for house dust mite correlated with the RAST test, while APT for cat fur correlated with the SPT. The APT may be useful to evaluate aeroallergens in atopic dermatitis, but further work is needed to make it more reliable.

Study on the efficacy of ELA-Max (4% liposomal lidocaine) compared with EMLA cream (eutectic mixture of local anesthetics) using thermosensory threshold analysis in adult volunteers.

BACKGROUND: ELA-Max and EMLA cream are topical anesthetics that have been shown to have similar anesthetic efficacy in previous studies. OBJECTIVE: To evaluate the analgesic efficacy of ELA-Max in comparison with EMLA cream using a novel method of thermosensory threshold analysis. METHODS: A thermosensory analyzer was used to assess warmth- and heat-induced pain thresholds. RESULTS: No statistically significant difference was found in pain thresholds using either formulation. However, EMLA cream increased the heat-induced pain threshold to a greater extent than ELA-Max. Thermosensory measurement and analysis was well tolerated and no adverse events were encountered. CONCLUSIONS: EMLA cream may be superior to ELA-Max for heat-induced pain. This study suggests that thermosensory measurement may be another suitable tool for future topical anesthetic efficacy studies.

Clinical characteristics of pruritus in chronic idiopathic urticaria.

BACKGROUND: Although pruritus is a predominant symptom of chronic idiopathic urticaria (CIU) its clinical characteristics have not been explored. OBJECTIVES: To characterize the clinical pattern and sensory and affective dimensions of the itch experience, utilizing a comprehensive itch questionnaire. METHODS: A structured questionnaire based on the McGill pain questionnaire was used in 100 patients suffering from CIU randomly recruited from a tertiary referral centre. RESULTS: All 100 patients recruited with CIU completed the questionnaire. In 68 patients pruritus appeared on a daily basis. Most patients experienced their pruritus at night and in the evening (n = 83), and 62 reported difficulty in falling asleep. Pruritus involved all body areas, but mostly the arms (n = 86), back (n = 78) and legs (n = 75). Accompanying symptoms were a sensation of heat in 45 patients and sweating in 15. Most patients (n = 98) were prescribed antihistamines (mainly sedating), of whom 34 experienced long-term relief. The sensation of itch was reported to be stinging (n = 27), tickling (n = 25) and burning (n = 23). Seventy-six patients found their pruritus bothersome, 66 annoying and 14 complained of depression. The itch intensity at its peak was more than double that felt after a mosquito bite. The worst itch scores of those who felt depressed were significantly higher than of those who did not (P = 0.018). There was a positive correlation between the sensory and affective scores during worst itch (P < 0.001). CONCLUSIONS: This study describes the itch experienced in CIU, highlighting sensory and affective dimensions. The itch questionnaire was found to be a valuable tool for evaluating pruritus in CIU and its unique features.

Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus.

BACKGROUND: Although pruritus is the predominant and commonest feature of atopic dermatitis, its clinical characteristics have not been explored. OBJECTIVE: To characterize the clinical pattern and sensory and affective dimensions of the itch experience utilizing a comprehensive itch questionnaire. METHODS: A structured itch questionnaire based on the McGill pain questionnaire was given to 102 Chinese patients with known atopic dermatitis. RESULTS: There were 100 patients with atopic dermatitis who fully filled the questionnaire. In 87% of the patients pruritus appeared on a daily basis. It had a prolonged duration (mean duration 10.7 7.3 years). It involved all body areas mostly in the lower limbs (83%), flexures (76%), upper limbs (71%) and neck (65%). Itch intensity during its peak was nearly twice higher than the itch of a mosquito bite. Itching was most frequent at night (65%), and 84% of patients reported of difficulty falling asleep. Daily life activities which increased the severity of itch were sweat in 96%, dryness in 71%, stress in 71% and physical effort in 73%. The major factors which were found to reduce the intensity of pruritus included: bathing with cold water in 55% and cold ambient environment in 56%. Associated symptoms were heat sensation (51%), sweating (40%) and pain in the pruritic area (45%). The various anti-pruritic therapies had limited long-term effect. The pruritus was bothersome (52%) and a major distress to the patient. The affective score correlated to itch intensity during its peak (r = 0.4, P < 0.001). CONCLUSIONS: The study provided a detailed description of pruritus in atopic dermatitis with new data on affective and sensory dimensions and associated symptoms. The questionnaire was found to be a useful tool in characterization of itch.

Pemphigus vulgaris following varicella infection.

We describe a 26-year-old Indian man who presented with chickenpox and subsequently developed pemphigus vulgaris 17 days after initial resolution of lesions. The mechanism of progression from one disease to the other is postulated to be that of epitope spreading or molecular mimicry.

The effect of topically applied aspirin on localized circumscribed neurodermatitis.

BACKGROUND: Lichen simplex chronicus is a troublesome intractable itchy dermatosis, which may persist despite intensive topical treatments. Recently it has been demonstrated that topical aspirin solution with dichloromethane has a significant antipruritic effect in an experimentally induced itch. OBJECTIVE: The aim of this double-blind, crossover placebo trial was to evaluate the efficacy of this solution in the treatment of lichen simplex chronicus. METHODS: Twenty-nine patients with lichen simplex chronicus of at least 3 months' duration that did not respond to topical corticosteroids were randomized in a double-blind fashion to receive aspirin/dichloromethane solution in treatment period 1 for 2 weeks followed by placebo in treatment period 2 or placebo followed by aspirin in period 2 with a crossover design after a 2-week washout. The patients rated the pruritus intensity before and during therapy with a visual analog scale; a blinded investigator performed photographic assessment. RESULTS: A significant therapeutic response was achieved in 11 (46%) of the patients who completed the study compared with 3 patients (12%) receiving placebo. Overall, aspirin-treated patients experienced an average decrease in the visual analog scale of 2.18 +/- 2.86 versus 0.69 +/- 2.31 of those receiving placebo. The difference between the 2 treatments for week 2 was significant (P =.03). CONCLUSION: The study suggests that topical aspirin/dichloromethane might be a practical treatment for lichen simplex chronicus.

Comparison of allergic contact dermatitis cases in the private and subsidized clinics in the National Skin Centre, Singapore.

INTRODUCTION: This is an epidemiologic study to compare allergic contact dermatitis patients in the private and subsidized clinics. PATIENTS AND METHODS: All patients diagnosed to have allergic contact dermatitis in the National Skin Centre from January 1999 to June 1999 were studied retrospectively. RESULTS: More private patients were evaluated for allergic contact dermatitis than subsidized patients in the study period (138 vs. 99). The female-to-male ratio in the paying clinics was greater than in the subsidized clinics (3:1 vs. 1:1). The mean age was the same for both groups i.e., 40 years. There was a greater proportion of unskilled workers attending the subsidized clinic (24.2% vs. 5.4%). The mean duration of rash before evaluation was longer for paying patients than for subsidized patients (31 vs. 22 months), but this was not statistically significant. A significant proportion of the patients had a history of atopic disease and endogenous dermatitis. The most frequent sites for allergic contact dermatitis were the face, hands and the exposed areas of the limbs. The most common allergens were nickel, cobalt and fragrance in the paying patients; and nickel, chromate and fragrance in the subsidized patients. CONCLUSION: More female patients with allergic contact dermatitis and more atopic patients were seen in the private clinics. The forearms, fingers, feet and ears were more commonly affected in the subsidized patients.

Comparative study of pemphigus vulgaris and pemphigus foliaceus in Singapore.

This is a retrospective study of all patients diagnosed to have pemphigus in our centre over a 3 year period. The case records of all patients with pemphigus from January 1995 to December 1997 were analysed. Fifty patients were diagnosed to have pemphigus during the study period. The diagnoses were pemphigus vulgaris in 31 patients, pemphigus foliaceus in 16, paraneoplastic pemphigus in two and IgA pemphigus in one. The average titre of anti-intercellular antibodies in patients with pemphigus vulgaris (1:96) was higher than the titre in patients with pemphigus foliaceus (1:69). The average initial dose of prednisolone required for disease control in patients with pemphigus vulgaris (62 mg/day) was significantly higher than that required for patients with pemphigus foliaceus (44 mg/day). In our study population, pemphigus vulgaris is a more severe and chronic disease than pemphigus foliaceus, as reflected in the higher titre of anti-intercellular antibodies, higher dose of systemic corticosteroids required for control of the disease, the longer duration to achieve complete remission and longer follow-up period.

Occupational skin diseases in national servicemen and military personnel in Singapore, 1989-1999.

This is a study of occupational skin disease among military personnel and conscripts in Singapore. All military personnel and conscripts diagnosed with occupational dermatoses in the National Skin Centre, Singapore, between 1989-1999 were studied retrospectively. Conscripts and regulars comprised 7.3% of all occupational skin disease patients seen. All were male, with a mean age of 23 years. Irritant contact dermatitis was more common than allergic contact dermatitis, by 4.4:1. The most common vocations associated with occupational skin diseases are those involving vehicle repairs and maintenance (48%) and food handling (19%). The most common irritants were oil/grease (66%), wet work (23%) and solvents (18%). The most common allergens were food (40%) and chromates (20%). Military personnel and conscripts make up a significant proportion of occupational skin disease patients seen in Singapore.

A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: a controlled study.

BACKGROUND: Treatment modalities for keloids, which are commonly found in Asians, include intralesional corticosteroid injections and cryotherapy as well as a combination of these two modalities. Few studies have been performed in a controlled fashion to evaluate the efficacy of these treatments. OBJECTIVE: A controlled study, to evaluate the combined effect of intralesional corticosteroid injection with cryotherapy vs. intralesional corticosteroid or cryotherapy alone. METHODS: Ten patients completed the study: eight patients had at least three keloids and two had two keloids. Patients were treated for at least three sessions 4 weeks apart. The outcome of the lesions was compared between the treatments regarding the thickness of the lesion using a caliper and photographic assessment, and the presence of itch and pain before and after treatment using a visual analogue scale. RESULTS: In terms of thickness, the keloids responded significantly better to combined cryotherapy and triamcinolone vs. triamcinolone alone or cryotherapy alone (P < 0.001). Pain intensity was significantly lowered with all treatment modalities; however, itch was lowered only with the combined treatment and intralesional corticosteroid alone. No significant side effects were noted with any of the treatments and no re-occurrence of keloids was noted with the combined therapy. CONCLUSION: Combined injection of intralesional steroids with cryotherapy appears to be superior to other current modalities.

The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis.

BACKGROUND: Many patients with psoriasis are known to suffer from itch. However, the data available regarding itch and its characteristics in psoriasis are sparse. OBJECTIVES: To examine the prevalence of pruritus and various related clinical characteristics in 101 patients with extensive psoriasis. METHODS: A structured questionnaire was used. RESULTS: Generalized pruritus was a feature of psoriasis in 84% of the patients. In 77% of these it appeared on a daily basis. It involved all areas of the body, had prolonged duration and appeared mainly in the evening and at night. The pruritus significantly affected quality of life. Important daily factors that were found to exacerbate the itch were ambient heat (81%), skin dryness (80%), sweating (65%) and stress (55%). Important factors that were found to ameliorate itch were sleep (57%) and cold showers (55%). The pruritus was found to be unresponsive to most available antipruritics, including phototherapy. Itch intensity as reflected by a visual analogue scale did not correlate with Psoriasis Area and Severity Index scores; however, a highly significant correlation was obtained between the affective descriptors and itch intensity in the worst itch states (r = 0.6, P < 0.001). CONCLUSIONS: Pruritus is a common feature of psoriasis and affects quality of life.

Tetracycline and nicotinamide for the treatment of bullous pemphigoid: our experience in Singapore.

AIM OF STUDY: To study the efficacy of tetracycline (or doxycycline) and nicotinamide in the treatment of less extensive bullous pemphigoid. METHODS: An open trial of 11 patients with bullous pemphigoid. Treatment was initiated with tetracycline 1.5-2 g/day and nicotinamide 1.5-2 g/day and gradually tapered down. Doxycycline was substituted for tetracycline in patients who could not tolerate tetracycline due to gastrointestinal side effects or headache. RESULTS: 6 out of 11 patients achieved complete response (> 90% decrease in lesions) while another 2 had partial response (50-90% decrease in lesions). CONCLUSION: Tetracycline/doxycycline and nicotinamide is a useful alternative treatment for localized bullous pemphigoid, especially in those whose concurrent medical illnesses preclude the use of systemic corticosteroids.

Epidemiology of occupational skin disease in Singapore 1989-1998.

This is an epidemiologic study of occupational skin disease in Singapore. All patients diagnosed with occupational dermatoses in the National Skin Centre, Singapore, over the 10-year period 1989-1998 were studied retrospectively. Irritant contact dermatitis was found to be more common than allergic contact dermatitis. The major sources of occupational dermatitis in Singapore were the metal/engineering, building/construction, electrical/electronics and transport industries. The main irritants were detergents/wet work, solvent and oil/grease. The main allergens were chromate, rubber chemicals and nickel. We concluded that the main sources of occupational skin disease and main allergens in Singapore had remained the same compared to a similar study of occupational skin diseases in 1984-85. Weak irritants are still the predominant causes of occupational irritant contact dermatitis, though the main irritants have changed compared to the previous study, where cutting fluids, cement and solvent were the most common irritants.

An unusual case of cutaneous vasculitis.

INTRODUCTION: We report an unusual case of a patient with clinical and histological features of cutaneous vasculitis. CASE PICTURE: A middle-aged Chinese male presented with livedo reticularis and digital gangrene without visceral involvement. Skin biopsy showed features suggestive of cutaneous vasculitis. Repeated testing for anticardiolipin antibody was negative. TREATMENT: He was treated with two courses of intravenous prostacyclin and pulsed with one course of intravenous methylprednisolone. He was also put on oral prednisolone, pentoxifylline, aspirin, nifedipine and colchicine in addition to symptomatic therapy. OUTCOME: There was gradual improvement of his toe discolouration and relief of pain. CONCLUSIONS: This is an interesting case of cutaneous vasculitis, which has features of polyarteritis nodosa and the antiphospholipid syndrome, who responded well to intravenous prostacyclin, steroids, pentoxifylline, aspirin, nifedipine and colchicine.