Healing Of Skin Lesions Research Articles

Ethambutol and pyrazinamide-induced toxic epidermal necrolysis in an immunocompetent adult with tuberculosis

Ethambutol and pyrazinamide-induced toxic epidermal necrolysis in an immunocompetent adult with tuberculosis

Western Pacific ALS-PDC: a prototypical neurodegenerative disorder linked to DNA damage and aberrant proteogenesis?

Western Pacific ALS-PDC: a prototypical neurodegenerative disorder linked to DNA damage and aberrant proteogenesis?

Clinical Follow-up of Patients with Myeloproliferative Neoplasms Presenting Skin Ulcers During Treatment with Hydroxyurea

Abstract 5157Hydroxyurea (HU) is widely employed in the treatment of Myeloproliferative Neoplasms (MPN); however, painful skin ulcers are a limiting toxicity during HU treatment in >5% of patients. To evaluate the clinical impact of such complication on the outcome of these patients, we retrospectively revised 1001 cases (M/F 437/564, median age 65.6 years, IR 55.6 – 73.7) with MPN consecutively diagnosed at 6 Centers in Rome who received HU treatment during the course of disease. There were 537 patients with Essential Thrombocythemia (ET), 336 with Polycythemia Vera (PV), 102 with Primary Myelofibrosis (PMF) and 26 with unclassifiable Chronic Myeloproliferative Disorders (CMPD-u); 863 patients (86.2%) received HU as 1st line treatment while 138 (13.8%) as 2nd or 3rd line treatment. On the whole, 71 patients (7.1%) developed painful skin ulcers after a median period of 54.1 months (IR 27.7 – 97.6) from HU start; as concerns the site, in 56/71 patients (78.8%) skin ulcers were located in the perimalleolar area while in the remaining 15 patients in other skin areas (localized to the head or to the extremities in 8 and 7 patients, respectively). When the skin ulcers occurred, HU treatment was continued at the same dosage in 11 patients (15.4%), was reduced in 13 patients (18.4%) and temporarily interrupted in 11 patients (15.4%): the remaining 36 patients (50.8%) needed a permanent drug discontinuation. Among these latter patients, pipobroman was started in 20 patients, anagrelide in 5, alpha-interferon in 3, melphalan in 3; in addition, no further treatment was given in 1 patient and 4 patients were lost to follow-up. As to ulcer resolution, 11/71 patients were not evaluable (2 too early, 9 lost to follow-up). Among the 60 evaluable patients, after a median period of 6.3 months (IR 3.6 – 11.3) from the onset of the skin ulcers, 43 patients (71.6%) had a complete resolution and 17 patients (28.4%) had an improvement without complete resolution. The incidence of 2nd neoplasia [3/71 (4.2%) patients with skin ulcers vs 73/930 (7.8%) patients without skin ulcers] and blastic phase evolution [2/71 (2.8%) patients with skin ulcers vs 41/930 (4.4%) patients without skin ulcers] were not increased after the skin ulcer occurrence. After a median period from skin toxicity of 30.7 months (IR 14.3 – 63.6), 9 patients were lost to follow-up, 11 patients died and 51 patients are still alive. In conclusion, painful skin ulcers during HU treatment are a relatively common complication in MPN patients, require HU discontinuation in > 50% of cases and in a sizable rate of patients there is only a partial healing of skin lesion: however, this complication and the requested treatment changes do not seem to impact on the subsequent clinical follow-up of MPN patients. Disclosures:No relevant conflicts of interest to declare.

Traitement par la dapsone des formes cutanées chroniques du purpura rhumatoïde : à propos de 3 cas

We describe 3 cases of chronic purpuric skin lesions in children suffering from systemic vasculitis: 3 children with Henoch-Schönlein purpura. Dapsone was introduced when skin lesions were recurrent, extensive, and persistent, due to its known ability to act as an anti-IgA and as an anticytotoxic agent against polynuclear neutrophils. Fast and complete but purely suspensive healing of skin lesions was noted. One child developed methemoglobinemia, a known side-effect of dapsone, highlighting the need for adequate prescription and follow-up.

Histopathology of culture‐associated skin erosions and papillary hyperplasia of Atlantic halibut, Hippoglossus hippoglossus (L.)

Atlantic halibut, Hippoglossus hippoglossus (L.), that were cultured in tanks with a smooth bottom (gel-coated fibreglass) substrate developed papillary hyperplasia and skin erosions on the blind (ventral) side. No viruses, bacteria or parasites were observed in any sections of affected skin. Comparison of microscopic pathology with that of skin from normal, wild-caught halibut showed severe epidermal proliferation with foci of severe mucous cell hyperplasia. Both epidermal thickness and mucous cell density were significantly greater in fish held on a smooth substrate compared to skin of healthy fish. Spongiosis was present, especially at the base of the papillary, hyperplastic epidermis, and there was a chronic inflammatory infiltrate in the scale pockets composed of lymphocytes, histiocytes and erythrocytes. Skin erosions had various degrees of epidermal loss, in some cases to the basement membrane. A predisposing factor for the epidermal sloughing may have been related to the spongiosis, and the vacuolated, degenerated basal cells. When affected halibut were cultured for an additional 28, 62 or 97 days on a sand substrate, which is conducive to skin lesion healing, there was no apparent change in epidermal thickness over time. However, mucous cell density significantly increased from day 0 to 97 during the healing process.

In Vivo Comparison of Simple and Double-Fractionated Low-Level Laser Irradiation Schemes on the Healing of Rat Skin Lesions

To compare the efficacy of a simple irradiation scheme with that of a double-fractionated irradiation scheme on the healing of rat skin lesions using in vivo monitoring of tissue diffuse reflectance. Low-level laser therapy (LLLT) is used in medicine for treating a wide range of pathological conditions. The practical benefits of laser treatment of acute and chronic conditions were obtained, using a single session of irradiation per day. Thirty Wistar rats were divided into three experimental groups (controls, simple laser irradiation scheme, and double-fractionated laser irradiation scheme). A skin lesion was created on the calf of the right hind leg of all rats. The laser irradiation parameters were lambda = 635 nm and power = 15 mW. The exposure time was 600 s for the simple laser irradiation scheme and 300 s x 2 for the double-fractionated laser irradiation scheme on 3 consecutive days. The optical properties of tissue were studied by processing and analyzing the diffuse reflectance spectra of injured skin, acquired before and after each laser irradiation. The results demonstrate that, using a simple laser irradiation scheme (single daily irradiation session: t exp 1 =600 s, power = 15 mW, lambda = 635 nm), healing of the skin lesion began after 3 consecutive treatment days. The application of the double-fractionated laser irradiation scheme (2 daily irradiation sessions: t exp 2 = t exp 1/2 = 300 s, power = 15 mW and lambda = 635 nm) led to a reduction in treatment time to 2 days. In conclusion, a double-fractionated irradiation scheme is more efficient than simple irradiation scheme for LLLT in rat skin lesions.

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Narrowband ultraviolet B (NB-UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. To examine whether NB-UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB-UVB on antimicrobial peptide and cytokine expression in the skin. Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB-UVB exposures on the whole body, given three times a week. Serum calcidiol (25-hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real-time quantitative polymerase chain reaction. At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L(-1)). NB-UVB treatment significantly increased (P < 0.001) serum calcidiol. The increase was 59.9 nmol L(-1) (95% confidence interval, CI 53.5-66.9) in psoriasis, 68.2 nmol L(-1) (95% CI 55.4-80.1) in AD and 90.7 nmol L(-1) (95% CI 63.8-123.4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0.001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human beta-defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB-UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB-UVB caused a marked but nonsignificant decrease of interleukin (IL)-1beta and IL-17 in psoriasis lesions. The present study shows that in addition to a significant improvement of psoriasis and AD, NB-UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.

Immunolocalization of heat shock proteins 27 and 47 during repair of induced oral ulcers

Heat shock proteins (Hsps) 27 and 47 are involved in the control of apoptosis, cell migration, and collagen synthesis. There is some understanding of the immunolocalization of these proteins during the repair process in skin and gastrointestinal mucosa, but their expressions in normal and injured oral mucosa are unknown. The aim of this study was to analyze the immunolocalization and intensity of these proteins in oral ulcers induced in rats and to compare these expression levels with those reported in skin and gastric mucosa. Ulcers were induced on the ventral surface of the tongues of rats. The rats were then euthanized at 0, 24, 48, 72, and 120 h. Hsp27 expression remained low in the first hours of repair, but was higher at 72 h, mainly in the migrating epithelium. Expression of Hsp47 was high at 48 h, mainly in fibroblasts, cells of the vascular wall, and basal keratinocytes of migrating epithelium. In the control group, expressions of these proteins were low, which indicates that these Hsps are constitutive proteins in oral mucosa. Expression levels were similar to those reported in the healing of skin lesions and gastric ulcer, suggesting a common mechanism of Hsp activation in the repair of these tissues.

Repeated episodes of fixed eruption 3 months after discontinuing pegylated interferon-α-2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus infection

We report a 73-year-old man who developed repeated episodes of erythematous, bullous plaques beginning 3 months after discontinuation of combination treatment with pegylated interferon (IFN)-alpha-2b and ribavirin for hepatitis C virus infection. The first episode resolved within a week without treatment, but the lesions recurred about once a month and were associated with high fever. Physical examination found darkly reddish, pigeon-egg-sized erythematous plaques with occasional flaccid blisters, predominantly on the trunk and proximal limbs, lip and penis. Histological examination showed well-demarcated foci of full-thickness epidermal necrosis and exocytosis of lymphoid cells. Pegylated IFN-alpha2b and ribavirin produced no response in lymphocyte stimulation tests. Systemic prednisolone led to rapid healing of skin lesions at the time of the fifth episode, leaving pigmented macules, but lesions recurred at the same sites within weeks of discontinuation of this treatment. It is uncertain whether this case represented a prolonged drug rash provoked by pegylated IFN-alpha2b or a fixed eruption in response to another antigen.

Effects of low intensity laser irradiation during healing of skin lesions in the rat

To determine whether laser light can improve healing of skin wounds by killing wound bacteria while simultaneously accelerating host tissue activity. Wounds on the rat dorsum were irradiated or sham-irradiated three times weekly from days 1 to 19 using 635 or 808 nm diode lasers at 1 or 20 J/cm(2). Wound area and bacterial growth were evaluated three times weekly. Histological analysis was performed on days 8 and 19. Immunohistochemical analysis was performed on day 19. Wounds that were irradiated using 635 nm light at 1 J/cm(2) healed similarly to controls. Wounds that were irradiated using 808 nm (1 and 20 J/cm(2), P<or=0.05) and 635 nm light (20 J/cm(2), P<or=0.05) were worse in wound maximum area at day 3 compared with controls. Further, 635 nm light at 20 J/cm(2) delayed wound closure at day 19 (ASL = 0.0127). Bacterial colonization of wounds was altered using 635 nm (20 J/cm(2), P<0.0001) and 808 nm light (1 J/cm(2), P<0.0001; 20 J/cm(2), P = 0.02). In particular, the presence of normal skin flora decreased (P<0.0001-0.0002) and, when using 808 nm light, the presence of S. aureus increased (P = 0.0001). There was histological evidence of advanced repair using 635 nm at 1 J/cm(2) at day 8 (ASL<0.04). In contrast, markers of acute repair were increased and of late repair were decreased at day 19 using 635 nm at 20 J/cm(2) (ASL<0.04). This study demonstrates that while clearing wounds of certain bacteria is feasible it does not necessarily translate into a healing advantage. When normal flora are disturbed, environmental organisms more readily colonize the wound surface. It is not clear when using 808 nm light whether the loss of normal flora in the wound alone is responsible for the proliferation of S. aureus or whether the light adds to the effect by stimulating S. aureus growth.

A zoonotic focus of cutaneous leishmaniasis in Addis Ababa, Ethiopia

BackgroundCutaneous leishmaniasis (CL) is endemic in the highlands of Ethiopia, and almost always caused by Leishmania aethiopica. Hitherto, Addis Ababa (the capital city of Ethiopia) was not considered endemic for CL, mainly due to absence of epidemiological and field ecological studies. This report summarizes the preliminary epidemiological investigation that proved the existence of active transmission in southeastern Addis Ababa.ResultsActive case finding surveys were conducted in 3 localities, Saris, Kality, and Akaki, which are found in and around Bulbula-Akaki river gorges. During the surveys conducted in January 2005 - May 2006, a total of 35 cases with 9 active and 26 healed skin lesions were identified. Eighteen of the cases (51.4%) were found in Saris; while 10 (28.6%) and 7 (20%) cases were from Kality and Akaki respectively.Ten colonies of rock hyraxes (Heterohyrax brucei) were identified in the vicinities of the 3 localities. Three of the 48 hyraxes (6.3%) trapped from the surroundings harbored natural infections of Leishmania aethiopica. Confirmation of the Leishmania species of the 3 isolates was achieved by PCR amplification and RFLP analysis of the ribosomal DNA internal transcribed spacer (ITS) sequences. Based on sandfly species composition and proximity of resting sites to human settlements, Phlebotomus longipes is circumstantially proven to be the vector of CL in south east Addis Ababa.ConclusionThe study proves the existence of isolated zoonotic foci of CL in south eastern Addis Ababa, with P. longipes as the likely vector and H. brucei as the natural reservoir host.

Genome-wide gene expression profiling analysis of Leishmania major and Leishmania infantum developmental stages reveals substantial differences between the two species

BackgroundLeishmania parasites cause a diverse spectrum of diseases in humans ranging from spontaneously healing skin lesions (e.g., L. major) to life-threatening visceral diseases (e.g., L. infantum). The high conservation in gene content and genome organization between Leishmania major and Leishmania infantum contrasts their distinct pathophysiologies, suggesting that highly regulated hierarchical and temporal changes in gene expression may be involved.ResultsWe used a multispecies DNA oligonucleotide microarray to compare whole-genome expression patterns of promastigote (sandfly vector) and amastigote (mammalian macrophages) developmental stages between L. major and L. infantum. Seven per cent of the total L. infantum genome and 9.3% of the L. major genome were differentially expressed at the RNA level throughout development. The main variations were found in genes involved in metabolism, cellular organization and biogenesis, transport and genes encoding unknown function. Remarkably, this comparative global interspecies analysis demonstrated that only 10–12% of the differentially expressed genes were common to L. major and L. infantum. Differentially expressed genes are randomly distributed across chromosomes further supporting a posttranscriptional control, which is likely to involve a variety of 3'UTR elements.ConclusionThis study highlighted substantial differences in gene expression patterns between L. major and L. infantum. These important species-specific differences in stage-regulated gene expression may contribute to the disease tropism that distinguishes L. major from L. infantum.

Live attenuated Leishmania vaccines: a potential strategic alternative

Leishmaniasis causes significant morbidity and mortality worldwide, constituting an important public health problem. Leishmania infections cause a wide spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Attempts to develop an effective vaccine to control leishmaniasis have been shown to be feasible, but no vaccine is in active clinical use. The ability to create genetically modified parasites by eliminating virulence or essential genes is considered a powerful alternative in the development of an effective protective vaccine. Here, recent findings related to genetically defined live attenuated Leishmania parasites as promising vaccine candidates are reviewed.

Effects of low-level laser therapy on the progress of wound healing in humans: the contribution of in vitro and in vivo experimental studies

Low-level laser therapy is an important method for the treatment of healing processes, and several experimental studies have been carried out in search of a greater understanding of its therapeutic possibilities. The objective of this study was to review pathogenetic aspects of soft tissue repair to better understand skin lesion healing and the role of low-intensity laser in the progression of tissue healing. This study consists of a concise review of scientific literature data on the use of low-level laser and its influence on wound healing. Many studies have extensively covered the effects of using laser radiation in tissues, describing its beneficial aspects in tissue healing. However, many unanswered questions demand research on the mechanism of action and on parameters of low-level laser use in different stages of wound repair to clarify how this method acts at a cell level in healing processes.

TOXIC EPIDERMAL NECROLYSIS/STEVENS–JOHNSON SYNDROME: CURRENT TRENDS IN MANAGEMENT

Toxic epidermal necrolysis (TEN) is an uncommon but potentially life-threatening condition that involves sloughing of the skin at the dermoepidermal junction. TEN is a well-recognized syndrome and is part of a range of severe mucocutaneous intolerance reactions, mostly elicited by drugs and/or their metabolites. Reported mortality rates vary widely from 20 to 75%. Several systemic treatment protocols for TEN have been published; however, none has been formally standardized in a randomized controlled trial. The present study documents the current management principles and trends seen in 16 patients admitted with TEN or Stevens-Johnson syndrome over a 5-year period at the Concord Repatriation General Hospital Burns Unit. Data were collected by retrospective chart review, and parameters included in the study were patient demographics, causative agents, percentage total body surface area and/or mucosal involvement, complications, treatment and outcome. In particular, dressing choice and documented healing of skin lesions were noted. Sixteen patients were identified, with the beta-lactam antibiotics most commonly implicated as the cause. Complications tended to relate to degree of sepsis and/or mucous membrane involvement. Nanocrsytalline silver dressings, such as Acticoat (Smith & Nephew, Mount Waverley, Victoria, Australia), were used predominantly in more recent cases. The shift in dressing choice from traditional Vaseline-impregnated gauze coincided with a general trend towards the use of nanocrystalline silver dressings for superficial burns after 2003. The nanocrystalline silver dressings have shown considerable advantage over previously used dressings, with no adverse reactions noted and good healing of the skin lesions for all patients.

IVIg selectively and rapidly decreases circulating pathogenic autoantibodies in pemphigus vulgaris

Background: Intraveneous immunoglobulin (IVIg) is increasingly used to treat pemphigus vulgaris (PV). The mechanism by which it does so is not known. The following study was conducted to confirm the effectiveness of IVIg for the acute control of active PV and to elucidate the mechanism by which it does.Methods: Twelve patients with active and severe PV unresponsive to conventional therapy with high doses of systemic steroids together with or without a cytotoxic drug were treated with a single dose of IVIg (400 mg/kg/day for 5 days). All patients were concurrently given cyclophosphamide or azathioprine of not already on one of these two drugs. The primary end-points were healing of skin lesions, changes in serum levels of intercelular (IC) autoantibodies and in steroid doses one to 3 weeks after initiation of IVIg.Results: Within 1 week of initiating IVIg the activity of PV was controlled in most cases. Within 3 weeks the average baseline dose of systemic steroid was reduced by 40%. Serum levels of IC antibodies rapidly declined by an average of 59% within 1 week of initiating IVIg and by 70% within 2 weeks. The decrease was selective, as the average serum levels of antibody to varicella-herpes zoster did not decrease in the 4 patients in whom they were measured. The decrease in IC antibodies was inversely related to serum levels of total inmmunoglobulin (IgG). The decrease in IC antibodies was not due to blocking factors in the IVIg preparation and was too rapid to be due to suppression of IgG synthesis, suggesting that it resulted from increased catabolism.Conclusions: IVIg can rapidly control active PV unresponsive to conventional therapy by causing a selective and very rapid decline in the autoantibodies that mediate the disease. We believe it does so by increasing the catabolism of all serum IgG antibodies, and that this results in a selective decrease in only abnormal autoantibodies as catabolized normal anti bodies are replaced by those present in the IVIg preparation. IVIg is the first treatment that achieves the ideal therapeutic goal in auto-antibody diseases, the selective removal of the pathogenic antibodies without affecting the level of normal antibodies.

Green Light Emitting Diode Irradiation Enhances Fibroblast Growth Impaired by High Glucose Level

The chronic metabolic disorder diabetes mellitus is an important cause of morbidity and mortality due to a series of common secondary metabolic complications, such as the development of severe, often slow healing skin lesions. In view of promoting the wound-healing process in diabetic patients, this preliminary in vitro study investigated the efficacy of green light emitting diode (LED) irradiation on fibroblast proliferation and viability under hyperglycemic circumstances. To achieve hyperglycemic circumstances, embryonic chicken fibroblasts were cultured in Hanks' culture medium supplemented with 30 g/L glucose. LED irradiation was performed on 3 consecutive days with a probe emitting green light (570 nm) and a power output of 10 mW. Each treatment lasted 3 min, resulting in a radiation exposure of 0.1 J/cm2. A Mann-Whitney U test revealed a higher proliferation rate (p = 0.001) in all irradiated cultures in comparison with the controls. According to these results, the effectiveness of green LED irradiation on fibroblasts in hyperglycemic circumstances is established. Future in vivo investigation would be worthwhile to investigate whether there are equivalent positive results in diabetic patients.

Zoster Paresis of the Shoulder -A case report-

Segmental motor paresis is a rare complication of acute herpes zoster. If skin rashes are present, herpes zoster related motor paresis could easily be suspected. However, the diagnosis may be difficult, especially when motor paresis occurs before the skin lesions or when motor paresis occurs several weeks after the skin lesions have healed. We experienced a cervical zoster patient whose shoulder paresis happened suddenly seven weeks after skin lesion healing. We diagnosed the patient as having a rotator cuff tear and scheduled repair. But we were confused by discordance between clinical symptoms and radiological findings. Eventually, EMG findings revealed the patient's paresis was derived from neuropathy not from rotator cuff tearing. Elective surgery was canceled and the patient recovered completely from the paresis.

Treatment of pemphigus with intravenous immunoglobulin

Background: Intravenous immunoglobulin (IVIg) has recently been advocated as a treatment for pemphigus, but the results of published studies are in conflict. This study was conducted to re-examine the effectiveness of IVIg for the immediate control of active disease and to study the mechanisms of its action. Methods: Six patients with active pemphigus vulgaris unresponsive to conventional therapy with high doses of corticosteroids were treated with IVIg (400 mg/kg per day for 5 days) and concurrently given cyclophosphamide (100-150 mg/d). The primary end points were healing of skin lesions and changes in the level of intercellular antibodies and steroid dose. Results: New lesions ceased to form within 1 week of initiating IVIg therapy, and within 2 weeks the extent of existing skin lesions was reduced by 80% or more in all but one patient. Within 3 weeks, steroid doses were reduced by an average of 41%. The improvement was more rapid than that in patients previously treated with similar doses of steroids and cytotoxic agents at the same institution. Clinical improvement was associated with a rapid decline in pemphigus antibodies whose levels decreased by 72% within 1 week of initiation of IVIg therapy. The rapidity and extent of this decline were similar to those achieved with intensive plasmapheresis. The decline was not due to blocking the synthesis or the immunologic activity of intercellular antibodies by IVIg, suggesting that it resulted from increased immunoglobulin catabolism. Conclusions: These results indicate that IVIg can effectively and rapidly control active pemphigus unresponsive to conventional therapy and suggest that the mechanism of its action is decreasing serum levels of intercellular antibodies. (J Am Acad Dermatol 2002;47:358-63.)

Clinical characteristics and prognostic significance of preherpetic neuralgia

Herpes zoster is a world-wide disease of older age commonly presenting with preherpetic pain. The aim of the study was to determine clinical characteristics of preherpetic neuralgia and its influence on occurrence of postherpetic neuralgia. A prospective, controlled trial included 88 patients with preherpetic neuralgia. 44 herpes zoster patients without preherpetic neuralgia were included in the control group. All of them were clinically followed-up for three months after complete healing of skin lesions. Older age (> 60 years) was significantly predominant (59.1%) compared with other age groups (p < 0.01) as well as female sex (59.9%) compared with the male sex (p < 0.01). There was no significant predominance of any type of preherpetic neuralgia (stabbing, burning, itching, dull pain). More intense preherpetic pain (reported as "severe" and "moderate") was established more often than mild pain. The mean duration of preherpetic pain was 4.4 days (ranged between 1-20 days). Postherpetic neuralgia developed in 36/88 patients with preherpetic neuralgia (affecting predominantly older than 50 years of age--31/36), but there was no significant difference in proportion of postherpetic neuralgia (PHN) according to those without preherpetic neuralgia. People older than 60 years are the most common age group among herpes zoster patients suffering from preherpetic neuralgia. Sex distribution of patients with preherpetic pain reveals highly significant predominance of female sex. Opposite to some other authors' reports, preherpetic neuralgia and its severity have not been proven as risk factors for postherpetic neuralgia in patients involved in our trial.