The use of intralesional corticosteroid combined with narrowband ultraviolet B in vitiligo treatment: clinical, histopathologic, and histometric evaluation.

BACKGROUND: Treatment of vitiligo with intralesional steroid (ILS) injections has shown to be successful in quite a few studies. It is a simple and safe treatment when used with caution with a better response in localized lesions. OBJECTIVES: The aim of the present study is to explore the efficacy and safety of using different concentrations of intralesional corticosteroid combined with NB-UVB phototherapy in the treatment of non-segmental vitiligo (NSV) patients. METHODOLOGY: Twenty patients with non-segmental vitiligo were subjected to different concentrations of ILS injections (triamcinolone acetonide); that was carried out monthly for six sessions. All patients were also subjected to twice-weekly sessions of NB-UVB for 6 months. Punch biopsy was taken from each patch before and at the end of treatment sessions. Each biopsy was stained with hematoxylin and eosin (H&E), Orcein, and Masson's trichrome stains. RESULTS: There was a significant difference between all groups in their repigmentation response (P = 0.017). After treatment, the epidermal thickness (histometry) was decreased (epidermal atrophy), especially with concentrations of 2.5 and 5 mg/ml of intralesional triamcinolone acetonide injection with decreased and disorganized collagen fibers. CONCLUSION: Intralesional corticosteroid injections combined with NB-UVB showed a good and well-tolerated therapeutic option for vitiligo. The concentrations of 0.625 and 1.25 mg/ml of triamcinolone acetonide were the safest with fewer side effects and complications. However, higher concentrations of 2.5 and 5 mg/ml were more effective but with more side effects.

Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study.

BACKGROUND: NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking. PURPOSE: To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V). METHODS: This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6 months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity. RESULTS: In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control. CONCLUSION: NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance.

Noncultured epidermal suspensions obtained from partial-thickness epidermal cuts and suction blister roofs for vitiligo treatment: A prospective comparative study.

BACKGROUND: The treatment options for vitiligo are either nonsurgical, including medical treatments and phototherapy, or surgical, including autologous transplantation methods. Noncultured epidermal suspension transplantation is indicated for the treatment of stable vitiligo not responding to either medical treatment or phototherapy. Variable results have been reported for the various techniques used for the preparation of this suspension. AIM: To compare the outcome between suction blister roof grafts and partial-thickness epidermal cuts for the preparation of noncultured epidermal suspensions for the treatment of stable vitiligo. PATIENTS AND METHODS: Forty patients with localized stable vitiligo lesions resistant to conventional therapy were included in the study. They were randomly divided into two groups for treatment with noncultured epidermal suspension grafting. The suspensions in groups I and II were obtained from suction blister roofs and partial-thickness epidermal cuts, respectively. Repigmentation grade, color match with the surrounding skin, and any side effects were compared between the groups. RESULTS: In group I, complete repigmentation was achieved in 6 cases while repigmentation was considered excellent in 8 cases; very good, 4 cases; and no response, 2 cases. In group II, complete repigmentation was achieved in 4 cases, and repigmentation was considered excellent in 16 cases. The color of the repigmented area matched the normal surrounding skin in 70% of the cases in group I and 40% of the cases in group II. CONCLUSION: Both techniques yielded comparable repigmentation results with advantages and disadvantages of both techniques.

Factors affecting the outcome of the suction blisters using two different harvesting techniques in vitiligo patients.

BACKGROUND: Suction blister grafting (SBG) technique has been used for long to treat various skin conditions. Different suction methods have been used such as syringes, Chinese cups, and suction device. There are some limitations of its use as time consumption, failure of induction or incomplete blister formation and pain. AIM: The aim of this work was to evaluate the outcome of using two different suction techniques, namely the syringes and the Chinese cups in induction of suction blisters. The effect of the device diameter and preheating of the donor area on the suction blister induction time (SBIT) was studied. The effect of saline injection in the blister formation and its completion was also evaluated. METHODS: The study was a left-right comparative study that included 50 patients with stable nonsegmental vitiligo. They were classified into four groups: Group 1 included 15 patients where different diameters of syringes (1.3, 1.7, and 2 cm) were compared against each other, group 2 included 15 patients where different diameters of cups (2, 3.5, and 5 cm) were compared against each other, group 3 included 20 patients subdivided into two groups; 10 patients each, where the effect of preheating the skin on blister induction was tested with use of cups (3a) and syringes (3b). Lastly, group 4 included randomly chosen 40 incomplete or multilocular blisters where the effect of saline injection on blister completion and coalescence of multilobulation was examined. SBIT was calculated in all patients. RESULTS: The use of the small diameter syringes or cups gave shorter SBIT; however, the difference, which was significant between all sizes of cups, was significant between the 1.3- and 2-cm-diameter syringes only. Preheating of the donor area shorten SBIT significantly. No complications were reported at the donor site except for transient postinflammatory hyperpigmentation in all patients. CONCLUSION: The small diameter syringes or cups and preheating of the donor area shorten the SBIT, while intra-blister saline injection increased the blister size and turns the multilocular blisters to unilocular ones.

Clinical evaluation of interrupted versus continuous narrowband ultraviolet B phototherapy in nonsegmental vitiligo treatment: A prospective randomized comparative study.

Phototherapy is the pillar of vitiligo treatment. One of its main obstacles is noncompliance. It was noticed that patients continue to repigment even after stopping sessions, so the idea of interrupted phototherapy emerged. To evaluate the effectiveness of interrupted versus continuous NB-UVB in nonsegmental vitiligo treatment. A prospective randomized comparative study of 23 patients with bilateral, nonsegmental vitiligo with no age or sex limits. All patients were treated with NB-UVB phototherapy for 1 month, after which one side of the body received continuous therapy (Side A) and the other received an interrupted course (Side B) for a total of 6 months. Two more groups of 10 patients were enrolled to exclude the systemic effect of NB-UVB. One group received continuous NB-UVB treatment, and the other received interrupted courses for 6 months. Evaluation of the results was performed clinically, by digital photography, planimetry and Vitiligo Area Scoring Index (VASI) prior to and 3 and 6 months after treatment. There was a significant clinical improvement in Group 1 compared to baseline (p < .05). However, there was no significant difference between the sides with regards to the clinical evaluation, point counting, and VASI scores (p > .05). When comparing the other two groups, there was a significant clinical improvement in each group after 6 months of treatment compared to baseline (p < .05), while there was no significant difference between them (p > .05). The current study suggests that interrupted NB-UVB phototherapy is a good alternative to continuous treatment with improved patient compliance, fewer side effects, and a lower cost of treatment.

Evaluation of different factors influencing objective measurement of skin color by colorimetry.

BACKGROUND: Objective determination of skin color has become an essential requirement in managing pigmentary disorders including vitiligo. The readings of available devices can be influenced by factors such as surrounding temperature, vasodilation/constriction, and skin surface properties. Our aim was to investigate the influence of hair color and length, skin stretching, incomplete contact of the device with the skin, and the pressure with which the device is applied to the test area on skin color determination. MATERIALS AND METHODS: Dermacatch® was used to determine the influence of hair color and length in 30 vitiligo patients, and of wrinkles, incomplete contact of the device with the skin and pressure of the device on the test area in 30 healthy volunteers on melanin and erythema indices measured by the device. RESULTS: Melanin index was significantly higher in lesions with black hair compared to lesions with white hair (P < 0.001) and the MI significantly decreased when the black hair was shaved (P < 0.001) and when the skin over the test area was stretched (P < 0.001). Incomplete contact of the device with the test area led to significantly higher MI (P < 0.001) and lower EI (P < 0.001). Meanwhile, high pressure induced by the device on the test area led to significantly lower MI (P < 0.001) and significantly higher EI (P < 0.001). CONCLUSIONS: Factors influencing the readings of devices used for objective determination of skin color have to be taken consideration to ensure accuracy of the measurements done.

Syringes versus Chinese cups in harvesting suction-induced blister graft: a randomized split-body study.

BACKGROUND: Suction blister grafting (SBG) is a technique where the pigmented epidermis is harvested from the donor site by induction of a blister using different suction methods as syringes, Chinese cups, suction device, etc. However, pain, time consumption, incomplete blister formation, and failure of blister development are the main limitations. OBJECTIVE: To compare between cups and syringes of similar diameter in inducing suction blisters. PATIENTS AND METHODS: In 30 patients with stable nonsegmental vitiligo, 2-cm-diameter (20 ml) syringe was applied on the anterolateral aspect of one thigh and a 2-cm-diameter cup on the corresponding site of the other thigh where right and left sides were chosen randomly. Patients were observed untill complete blister development or for a maximum of 3 hours. Suction blister induction time (SBIT) and the blister diameter were recorded for each patient. Pain during the process of induction was evaluated. RESULTS: Incomplete blister development was noted in 9 out of 30 (30%) with 2 cm syringes and 6 out of 30 (20%) with the similar diameter cups with no significant difference (P = 0.49). No significant difference was found between SBIT induced by the 2 cm syringes and the similar size cups (101.17 ± 68.14 minutes, 98 ± 56.84 minutes, respectively) (P = 0.85). Meanwhile, blister diameter induced by either syringe or cup was not significantly different (P = 0.37). Anesthesia was for short duration with xylocaine, and pain was intolerable in both sides in the first seven patients. A combination of xylocaine and bupivacaine was used with prolonged loss of pain in 17 of the remaining 23 patients and tolerable pain in six patients similarly in both sides. CONCLUSION: According to present results, the differences in SIBT, diameter of blisters, and number of complete blister formation induced by either syringes or cups of similar size were not significant. Therefore, whatever the available and feasible technique for the surgeon will be the ideal choice. A combination of xylocaine and bupivacaine is recommended to overcome the accompanying pain of the procedure.

The effect of latanoprost on vitiligo: a preliminary comparative study.

Latanoprost (LT), a prostaglandin F 2alpha (PGF2a ) analogue used in the treatment of glaucoma, was found to induce skin pigmentation in guinea pigs in addition to its known periocular and iridal pigmentation side effects. This study aims to evaluate the efficacy of topical LT in the induction of skin repigmentation in patients with vitiligo and to compare its potency with narrow band ultraviolet (UV) B (NB-UVB). The result of their combination was also assessed. This study involved 22 patients with bilateral and symmetrical vitiligo lesions, stable for the last three months, divided into three groups: group I, to evaluate LT vs. placebo; group II, to evaluate LT vs. NB-UVB; and group III, to evaluate the effect of their combination. The response to treatment was evaluated by taking photographic records of the treated lesions with follow-up photography every two weeks. After three months, assessment of the degree and extent of repigmentation was performed. Follow-up assessment was done six months after termination of the trial for the persistence of pigmentation, recurrence, or development of any side effects. LT was found to be better than placebo and comparable with the NB-UVB in inducing skin repigmentation. This effect was enhanced by the addition of NB-UVB. LT could be a promising treatment for vitiligo, especially the periocular variant. Its effect on skin repigmentation could be enhanced by NB-UVB exposure.

Beyond vitiligo guidelines: combined stratified/personalized approaches for the vitiligo patient.

'Vitiligo' is a word that bears endless possibilities and no promises. Each vitiligo patient has a different story that demands a different therapeutic approach. Even though great efforts have been made to evaluate, study, compare and document the different therapeutic modalities available for vitiligo, clearly handling their modes of actions as well as their side effects and establishing clear stratified guidelines, numerous dilemmas are frequently met on practical grounds. 'Stabilize', 'repigment', 'depigment' or 'camouflage'? 'for whom and how do we achieve the best results' ? 'Separately or in combination ? - questions that need to be answered and decisions need to be taken in the appropriate timing and altered when the necessity arises. In the current viewpoint, we have utilized the available knowledge and exploited years of experience in an attempt to go beyond the guidelines to set the rationale for an optimal and personalized therapy, within the framework of a stratified approach.

Effect of PUVA therapy on melanocytes and keratinocytes in non-segmental vitiligo: histopathological, immuno-histochemical and ultrastructural study.

BACKGROUND AND AIMS: Psoralen ultraviolet A (PUVA) is an important modality in treating vitiligo. Its effect on melanocytes and keratinocytes is not sufficiently studied. In this work, we investigated 30 cases of non-segmental vitiligo regarding the changes of melanocytes and keratinocytes in both vitiliginous and nearby areas before and after PUVA therapy. METHODS: Three skin biopsies were obtained from each patient from the vitiliginous, marginal and perilesional areas before and after 12 months of PUVA. Biopsies were examined histologically using haematoxylin and eosin, Masson-Fontana stains and 3,4-dihydroxyphenylalanine (DOPA) reaction and histochemically using human melanoma black-45 (HMB-45) antibody while ultrastructural examination was performed on six patients. Control biopsies were taken from five healthy volunteers. RESULTS: In 10% of pretreated biopsies from the centre of vitiligo lesions, scanty melanocytes were detected histologically and ultrastructurally, while they did not stain with DOPA or HMB-45 antibody suggesting that these melanocytes were inactive. Moreover, degenerative changes were detected by electron microscopy in both melanocytes and keratinocytes in all areas. After PUVA therapy, obvious improvement of the histopathological changes occurred with significant increase in active melanocytes. The degeneration of melanocytes and keratinocytes was also reduced at the ultrastructural level. CONCLUSION: Vitiligo affects both melanocytes and keratinocytes causing degenerative changes. These changes were present in both the leucodermic and the apparently normal perilesional skin. PUVA increases the number of active epidermal melanocytes in the three tested areas and recovers the melanocyte and keratinocyte degeneration.

A new morphometric technique for assessment of melanization in skin of guinea pigs.

BACKGROUND: The degree of melanization is an important finding in many skin disorders. An objective measurement of melanin density is needed to achieve an accurate evaluation. OBJECTIVES: The present work aims at translating the subjective increase of melanin particles after narrow band ultraviolet-B (NB-UVB) irradiation into objective numerical values ready for statistical analysis. MATERIALS AND METHODS: This study had involved 18 guinea pigs that were exposed to biweekly sessions of NB-UVB radiation for 4 weeks to induce skin pigmentation. Two skin biopsies were obtained from each animal; the first before treatment and the second at the end of the study, using 5 mm punch and stained with hematoxylin and eosin and Masson-Fontana (MF) stains. Surface area of both the epidermis (ESA) and the melanin particles (MPSA) were measured in µm(2) using a software supplied with Olympus light microscope. The MPSA/ESA percentage was calculated for each biopsy. The results before and after NB-UVB exposure were compared and statistically analyzed. RESULTS: In the MF-stained sections, the mean ± SD of the MPSA/ESA percentage were 0.24 µm(2) ± 0.09 and 6.21 µm(2) ± 2.45 at the start of the study and at its end, respectively, with a highly significant difference (P < 0.001). CONCLUSION: This technique offers a new methodology for an accurate numerical evaluation of epidermal melanization.

The effect of H1 and H2 receptor antagonists on melanogenesis.

BACKGROUND: Histamine was found to stimulate melanogenesis in cultured human melanocytes specifically mediated by histamine H 2 receptors via protein kinase A activation. Based on this finding, the effect of topically applied H 2 antagonist on UVB-irradiated Guinea pigs' skin was examined and found to be suppressive on the post-irradiation melanogenesis. AIMS: In this study, we tried to explore the role of topically applied H 1 and H 2 receptor antagonists, in inhibition of UVB-induced melanization. METHODS: The effect of topically applied H 1 and H 2 receptor antagonists in inhibition of melanization was done clinically and histochemically using Fontana Masson and DOPA reactions compared with placebo. RESULTS: The post-irradiation pigmentation was found to be brownish/black instead of the original light brown color. This color change occurred below the shaved orange-red fur suggesting a switch of melanogenesis from pheomelanin to eumelanin. The induced pigmentation was suppressed by topically applied H 2 antagonist while both H 1 antagonist and vehicle had no effect. The microscopic examination showed that the keratinocytes in the H 2 antagonist-treated areas contained few melanosomes while the nearby dendrites are full of them. CONCLUSION: H 2 antagonists' inhibition of UVB-induced pigmentation is not only due to suppression of melanization but also due to a specific action on melanosomes' transfer.

Patterns of repigmentation in two cases of hypopigmented type of vitiligo.

It has been observed that depigmentation in vitiligo passes through two stages; patches of light brown hypopigmentation which gradually changes into milky white patches. In this work, we studied two cases of hypopigmented vitiligo regarding the melanocytes and keratinocytes' changes before and after 7 months of psoralen plus ultraviolet A (PUVA) therapy. Skin biopsies were taken from the vitiliginous lesions before and after 7 months of PUVA therapy and were examined using haematoxylin and eosin and Masson Fontana stains, L-3,4-dihydroxyphenylalanine reaction, immuno-histochemical stains and ultrastructural examination. In the pretreated patients, the melanocytes present were inactive and degenerative changes were detected in both melanocytes and keratinocytes. After PUVA therapy, obvious histopathological improvement was detected. Clinically, the initial response to PUVA therapy was increased hypopigmentation indicating that degenerated cells in the vitiliginous patches might have continued the process of degeneration and did not recover. Meanwhile, the perifollicular and marginal pigmentation suggested that pigmentation occurred from those areas and not from activation of already degenerated melanocytes.

Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short-term NB-UVB phototherapy in the treatment of non-segmental vitiligo: a left-right comparative study.

BACKGROUND: NB-UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium-YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo. PURPOSE: In the present study, we are exploring the effect of the use of ER:YAG laser skin ablation and application of 5FU on the outcome of short-term NB-UVB therapy for patients with non-segmental vitiligo (NSV). METHODS: This study included 50 adult patients with a total of 65-paired symmetrical NSV lesions in different body parts. One side was treated with ER:YAG laser ablation, followed by 5FU application before simultaneous NB-UVB therapy of both sides for a maximum period of 4 months. The outcome was then evaluated both qualitatively and quantitatively. RESULTS: The overall response to therapy was better using the combination therapy. Fifty patients (78.1%) experienced a moderate-marked repigmentation response in the combination group compared with 23.4% in the mono-therapy group. The response was significantly higher when using the combination therapy in different body parts (P value is <0.05), except for feet lesions, which were better but not statistically significant (P value=0.15). Tolerable pain during ablation or at sites of 5FU application was reported in all cases. Transient hyperpigmentation occurred in 30% of cases and 3.1% of lesions healed by a transient slate blue color. Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient. CONCLUSION: We concluded that prior use of ER:YAG laser skin ablation, followed by 5FU application before NB-UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short-term NB-UVB therapy and is expected to increase patient compliance.

[The effect of preischemic blood sugar concentration on hemodynamics and regional organ blood flow during and following cardiopulmonary resuscitation (CPR) in swine]. / Zum Einfluss der präischämischen Blutzuckerkonzentration auf Hämodynamik und regionale Organdurchblutung während und nach kardiopulmonaler Reanimation (CPR) beim Schwein.

UNLABELLED: Blood glucose alterations prior to cerebral ischaemia are associated with poor neurologic outcome, possibly due to extensive lactic acidosis or energy failure. Cerebral effects of hyper- or hypoglycaemia during cardiopulmonary resuscitation (CPR) are less well known. In addition, little information is available concerning cardiac effects of blood glucose alterations. The aim of this study was to evaluate the effects of pre-cardiac-arrest hypo- or hyper-glycaemia compared to normoglycaemia upon haemodynamics, cerebral blood flow (CBF) and metabolism (CMRO2), and regional cardiac blood flow during CPR subsequent to 3 min of cardiac and respiratory arrest and after restoration of spontaneous circulation. METHODS: After approval by the State Animal Investigation Committee, 29 mechanically ventilated, anaesthetised pigs were instrumented for haemodynamic monitoring and blood flow determination by the radiolabeled microsphere technique. The animals were randomly assigned to one of three groups: in group 1 (n = 9) blood glucose was not manipulated; in group II (n = 10) blood glucose was increased by slow infusion of 40% glucose to 319 +/- 13 mg/dl; in group III (n = 10) blood glucose was lowered by careful titration with insulin to 34 +/- 2 mg/dl. After 3 min of untreated ventricular fibrillation and respiratory arrest, CPR (chest compressor/ventilator (Thumper) and epinephrine infusion) was commenced and continued for 8 min. Thereafter, defibrillation was attempted, and if successful, the animals were observed for another 240 min. Cerebral perfusion pressure (CPP), CBF, CMRO2, coronary perfusion pressure (CorPP), and regional cardiac blood flow were determined at control, after 3 min of CPR, and at 10.30, and 240 min post-CPR. RESULTS: In group 1. 4/9 animals (44%) could be successfully resuscitated; in group II 4/10 (40%); and in group III 0/10 (0%). Prior to cardiac arrest, mean arterial pressure, CPP, and CorPP in group III were significantly lower compared to groups I and II. In group I. CPP during CPR was 26 +/- 6 mmHg; CBF 31 +/- 9 ml/ min/100g CMRO2 3.8 +/- 1.2 ml/ min/100 g; CorPP 18 +/- 5 mmHg; and left ventricular (LV) flow 35 +/- 15 ml/min/100 g. In group II; CPP = 21 +/- 5; CBF 21 +/- 7; CMRO2 1.8 +/- 0.8; CorPP 16 +/- 6; and LV flow 22 +/- 9; and in group III: CPP 15 +/- 3; CBF 11 +/- 8; CMRO2 1.5 +/- 1.1; CorPP 4 +/- 2; and LV flow 19 +/- 10. During the 240-min post-resuscitation period, there were no differences in CBF, CMRO2, or LV flow between groups I and II. CONCLUSION: Hypoglycaemia prior to cardiac arrest appears to be predictive for a poor cardiac outcome, whereas hyperglycaemia does not impair resuscitability compared to normoglycaemia. In addition, hyperglycaemia did not affect LV flow, CBF, or CMRO2. However, it has to be kept in mind that haemodynamics and organ blood flow do not permit conclusions with respect to functional neurologic recovery or histopathologic damage to the brain, which is very likely to be associated with hyperglycaemia.