Severity Of Rash Research Articles

Etiology of Pruritic Papular Eruption With HIV Infection in Uganda

A frequent cause of human immunodeficiency virus (HIV)-related morbidity in sub-Saharan Africa is a commonly occurring, intensely pruritic skin rash. The resulting scars are disfiguring and stigmatizing. Despite the substantial prevalence of pruritic papular eruption (PPE) among HIV-infected Africans, the cause has been elusive. To determine the etiology of PPE occurring in HIV-infected individuals. Cross-sectional study of HIV-infected patients with active PPE from clinics in Uganda conducted from May 19 through June 6, 2003. Enrollment occurred in the month preceding May 19. Each participant was clinically examined by 2 dermatologists, had laboratory studies performed, was administered an epidemiologic questionnaire, and had a skin biopsy of a new lesion evaluated by a dermatopathologist. Histological characteristics of new pruritic lesions. Other assessments included CD4 cell count, eosinophil count, and physician-assessed rash severity. Of 109 patients meeting inclusion criteria, 102 (93.6%) completed the study. The CD4 cell counts in this study population were generally low (median, 46/microL) and inversely related to increasing rash severity (median CD4 cell counts: 122 for mild, 41 for moderate, and 9 for severe; P<.001 for trend). Eighty-six patients (84%; 95% confidence interval, 77%-91%) had biopsy findings characteristic of arthropod bites. Patients with arthropod bites on biopsy had significantly higher peripheral eosinophil counts (median, 330 vs 180/microL; P = .02) and had a trend toward lower CD4 cell counts (median, 40 vs 99/microL; P = .07) than those without histological evidence of arthropod bites. Pruritic papular eruption occurring in HIV-infected individuals may be a reaction to arthropod bites. We hypothesize that this condition reflects an altered and exaggerated immune response to arthropod antigens in a subset of susceptible HIV-infected patients.

591 p53 mutation with transdominance activity is an independent prognostic factor for endometrial cancer

Erlotinib (OSI-774; Tarceva™) is an orally available, highly specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The results of 3 phase II studies with erlotinib in non–small-cell lung cancer (NSCLC) are reviewed herein: (1) in patients with chemotherapy-resistant, HER1/EGFR-expressing NSCLC of all histologies, (2) in patients with bronchoalveolar carcinoma previously untreated or treated with chemotherapy, and (3) as first-line therapy in elderly patients with NSCLC of all histologies. These studies have evaluated tumor response, survival, and symptom improvement. Erlotinib was given as an oral, continuous daily dose of 150 mg. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in approximately two thirds of patients. Withdrawals caused by toxicity were rare. The response rates were 12.3%, 25%, and 13.3%, respectively. Mature survival data are available for the first trial. The median survival was 8.4 months, and the 1-year survival rate was 40%. All responding patients in the first and second trials presented skin rash. In addition, survival correlated with the occurrence and severity of rash in the first trial. No data on the correlation between rash and survival are available for the second and third trials. Erlotinib is active and well tolerated in patients with NSCLC as first- and second-line therapy. Cutaneous rash appears to be a surrogate marker of clinical benefit, but this finding needs to be confirmed in ongoing and future studies.

A safety, tolerability, and pharmacokinetic (PK) study of GW572016 in patients with solid tumors

3179 Background: GW572106 is a reversible inhibitor of ErbB1/ErbB2 tyrosine kinases. This phase I monotherapy study evaluated safety, tolerability, and PK in patients with advanced solid tumors at once (QD) and twice daily (BID) dosing schedules. Methods: Patients (pts) were administered GW572106 on a QD or BID continuous schedule. QD doses ranged from 175 to 1800 mg and BID doses were 500, 750, and 900 mg per dose. In addition to standard evaluations, serial MUGAs were obtained. PK on days 1 and 14 and disease assessments every 8 weeks (RECIST criteria) were obtained. Results: 81 pts with various carcinomas were enrolled; 64 pts (39 QD, 25 BID) included in safety and disease assessment; 57 included in PK. Median age was 62 yrs; 39 males/25 females. The majority of drug-related AEs were grade I (75% of pts QD, 71% pts BID). Diarrhea was the most frequent AE (17% QD, 29% BID of pts). Two pts had grade 3 diarrhea at 900 mg BID. Other AEs were fatigue (16%), nausea (16%) and rash (9%) on QD and nausea (11%) and rash (11%) on BID dosing. While serial MUGAs revealed no significant median change in LVEF, only 1 of the 81 pts experienced cardiac toxicity; a grade 2, asymptomatic decline in LVEF was observed. There were no clinically significant changes in the other safety evaluations. The severity of diarrhea and rash were not correlated with dose; severity of rash but not diarrhea appeared to correlate with serum concentration. Conclusion: Administration of GW572106 on a QD schedule was well-tolerated at all doses while 500 and 750 mg BID were better tolerated than 900 mg BID. The majority of AEs were grade 1 or 2 skin and/or GI toxicities, manageable with symptomatic treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline; Pharmacia GlaxoSmithKline Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline

Complex regional pain syndrome-like symptoms during herpes zoster

Complex Regional Pain Syndrome (CRPS) associated with herpes zoster (HZ) was first reported by Sudeck in 1901 (Sudeck, 1901) and is recognized clinically. However, only 13 cases have been published in the literature, and nothing is known about the incidence, prevalence, or natural history (Chester, 1992; Foster et al., 1989; Grosslight et al., 1986; Ketz and Schliack,1968; Kishimoto et al., 1995; Querol and Cisneros, 2001; Sudeck, 1901; Visitsunthorn and Prete, 1981). The aim of the present study was to determine the prevalence of CRPS-like symptoms in a prospectively gathered cohort of subjects with HZ and to follow the natural history of their pain and sensory disturbance during the first 6 months after onset of HZ. Subjects were evaluated at four time points after HZ: 2–6 weeks, 6–8 weeks, 3 months, and 6 months. Only subjects aged 50 or older with pain VAS ratings of ≥20/100 at 2–6 weeks were eligible. The first (screening) visit included a neurological and physical examination that was updated at each subsequent visit. Assessments included ratings of pain intensity, allodynia severity, and rash severity. The neurological exam included determination of presence or absence of the following CRPS-like symptoms: (1) increased sweating, (2) color changes, (3) skin temperature changes, (4) weakness of the affected area based on physical exam, (5) edema, and (6) extension of CRPS-like symptoms outside the affected dermatome. For subjects with HZ in dermatomes that can include the limbs (C4–T2 and L1–S2), extremity involvement was considered present if allodynia or rash extended beyond the neck of the humerus (upper extremity), the inguinal ligament (anterior lower extremity), or gluteal sulcus (posterior lower extremity). Involvement of the extremity was considered proximal if neither HZ rash nor allodynia extended past the elbow (upper extremity) or knee (lower extremity). Of the first 75 subjects recruited, 25 had HZ outbreaks in dermatomes that extended into the extremities (C4–T2 and L1–S2). In this group, 8 subjects had no extremity involvement, 8 had proximal extremity involvement, and 9 had distal extremity involvement. Subjects with distal extremity HZ reported more pain across the four visits ( p<0.05). At 3 months, more subjects with distal extremity involvement met criteria for PHN (8 out of 9, 89%), while only 4 out of 8 (50%) with proximal involvement and 2 out of 8 (25%) of subjects without extremity involvement met criteria for PHN (Chi-square test: p<0.05). Only 25 out of the remaining 50 (50%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN at 3 months (Chi-square test: p<0.05). Six months after onset of HZ, 6 out of 9 subjects with distal extremity involvement met PHN criteria compared with 2 out of 8 (25%) with proximal involvement and 2 out of 8 (25%) without extremity involvement (Chi-square test: p=0.12). Fifteen out of 50 (30%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN (Chi-square test: p<0.05). No subject had all six CRPS-like symptoms. Of the 17 subjects with extremity involvement, 9 subjects had ‘0–2 CRPS-like symptoms’ and 8 had ’3–5 CRPS-like symptoms’. None of the eight subjects without extremity involvement had any CRPS-like symptoms. Of the 50 subjects with HZ outside the extremity, only one had abdominal weakness. Pain ratings were higher in subjects with ‘3–5 CRPS-like symptoms’. More subjects with ‘3–5 CRPS-like symptoms’ met criteria for PHN at 3 months (7 out of 8, 88%), compared to 5 out of 9 (55%) of subjects with ‘0–2 CRPS-like symptoms’ ( p=0.07). At 6 months, 2 out of 9 (22%) of subjects with ‘0–2 CRPS-like symptoms’ met criteria for PHN, compared with 6 out of 8 (75%) of subjects with ‘3–5 CRPS-like symptoms’ (Chi-square test: p<0.03). Two case-reports are presented. In summary, the occurrence of CRPS-like symptoms is common in subjects with HZ outbreaks affecting the extremity, particularly if the distal extremity is involved. It is uncertain if the pathophysiology underlying the CRPS-like symptoms observed in this study is similar to that of CRPS from other causes, or if it is relatively specific to HZ. Development of PHN is common in subjects who have experienced CRPS-like symptoms. More aggressive preventive treatments may be justified in this high-risk subset of HZ subjects to prevent development of PHN. Prospective randomized controlled studies are needed to determine which subjects are most likely to benefit and when treatment should begin.

The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer.

Erlotinib (Tarceva) is a reversible and highly specific inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Phase I studies established a fixed daily oral dose of 150 mg as the recommended dose for Phase II studies. Using this dose and schedule, the response rate in a group of 57 patients with EGFR-positive non-small cell lung cancer after failure of platinum-containing chemotherapy was 12%. The median survival was 8.4 months, and the 1-year survival was 40%. Occurrence and severity of rash were correlated with an improved survival independently of performance status. Another ongoing Phase II study in 50 patients with bronchoalveolar carcinoma has shown a response rate of 26%. Results from two Phase III front-line studies in combination with chemotherapy, TALENT and TRIBUTE, have been recently reported. The addition of erlotinib did not improve response rate, time to progression, or survival. Efforts in the continued development of erlotinib should be focused on the following: (a) investigating the reasons for the lack of relationship between EGFR expression and clinical outcome; (b) the reasons for the failure of the front-line combination trials; and (c) confirming the rash/clinical outcome relationship. Progress in these tasks will allow a better selection of patients who can benefit from this therapy, permit the development of more effective combination schedules with cytotoxics, and define whether this agent should be used at the optimal biological dose or at the maximum-tolerated dose.

Novel agents in the treatment of lung cancer: conference summary statement.

A small, international, closed-door conference on Novel Agents in the Treatment of Lung Cancer, held in Cambridge, Massachusetts, October 17–18, 2003, was convened to present and discuss findings from recent and ongoing trials of investigational drugs for the treatment of lung cancer. Invited

May 11 Highlights

The AAN practice parameter by Sloan et al. reviews transcranial Doppler (TCD) and transcranial color-coded sonography (TCCS). TCD is of established value in screening children aged 2 to 16 years with sickle cell disease for stroke risk and for detecting and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage. Contrast-enhanced TCD can provide useful information in detection of right-to-left cardiac/extracardiac shunts. TCD and TCCS may have value for detection of intracranial occlusive disease, vasomotor reactivity, detection of cerebral circulatory arrest/brain death, monitoring carotid endarterectomy, and monitoring thrombolysis. see page 1468 In 965 patients with herpes zoster, Jung et al. found that in older women, the presence of a prodrome, greater rash severity, and acute pain each made an independent contribution to the development of postherpetic neuralgia (PHN). see page 1545 In two girls with severe developmental delay, seizures, nystagmus, and CNS hypomyelination, Wolf et al. found markedly elevated levels of N -acetylaspartylglutamate in CSF. The underlying genetic defect could not be elucidated. see page 1503 Fogli et al. evaluated MRI-based criteria to help select patients with an undetermined leukodystrophy who tested positive for EIF2B genes mutation. Disease severity from fatal infantile to adult asymptomatic …

Effect on quality of life in patients with pityriasis rosea: Is it associated with rash severity?

Effect on quality of life in patients with pityriasis rosea: Is it associated with rash severity?

Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia

Purpose Other than age, the risk factors for postherpetic neuralgia are not well established. We studied whether the concentration of interleukin 8 in the cerebrospinal fluid is associated with the risk of postherpetic neuralgia. Methods We enrolled 170 patients more than 50 years old who had a typical painful and nontrigeminal herpetic rash. Patients were treated with acyclovir; no corticosteroids were given. Cerebrospinal fluid was taken for analysis of interleukin 8 during and at full crusting of the herpetic rash. Age, sex, comorbid conditions, prodromal pain, localization and severity of herpetic rash, number of skin lesions, and degree of pain were recorded. We used multivariate logistic regression modeling to identify significant predictive factors. Receiver operating characteristic (ROC) curves were evaluated to determine the contribution of each factor. Results Six months after healing, 31 patients (18%) had postherpetic neuralgia; 27 patients still had it after 1 year. Only three variables—age (odds ratio [OR] = 2.7 per 10-year increase; 95% confidence interval [CI]: 1.2 to 6.2), acute pain (OR = 1.8 per unit increase in visual analog scale; 95% CI: 1.2 to 2.8), and interleukin 8 concentration in the cerebrospinal fluid at full crusting of the herpetic rash (OR = 1.6 per 20-μg/L increase; 95% CI: 1.3 to 2.0)—were significant predictors of postherpetic neuralgia at 1 year. Interleukin 8 concentration also had the highest area under the ROC curve at these evaluation points ( P <0.001). Conclusion Our results suggest that interleukin 8 concentration in the cerebrospinal fluid at full crusting of herpetic rash may be useful for identifying patients who are likely to develop intractable postherpetic neuralgia.

Management of herpes zoster (shingles) and postherpetic neuralgia

Herpes zoster (HZ) results from recrudescence of varicella zoster virus latent since primary infection (varicella). The overall incidence of HZ is ∼ 3/1000 of the population per year rising to 10/1000 per year by 80 years of age. Approximately 50% of individuals reaching 90 years of age will have had HZ. In ∼ 6%, a second attack may occur (usually several decades after the first). Patients with HZ can transmit the virus to a non-immune individual causing varicella. HZ is not contracted from individuals with varicella or HZ. Reduced cell-mediated immunity to HZ occurs with ageing, explaining the increased incidence in the elderly and from other causes such as tumours, HIV and immunosuppressant drugs. Diagnosis is usually clinical from typical unilateral dermatomal pain and rash. Prodromal symptoms, pain, itching and malaise, are common. The most common complication of HZ is postherpetic neuralgia (PHN), defined as significant pain or dysaesthesia present ≥ 3 months after HZ. PHN results from damage and secondary changes within components of the nervous system subserving pain. Some motor deficit is common; severe and long-lasting paresis may rarely accompany HZ. More than 5% of elderly patients have PHN at 1 year after acute HZ. Predictors of PHN are, greater age, acute pain and rash severity, prodromal pain, the presence of virus in peripheral blood as well as adverse psychosocial factors. Therapy for acute HZ is intended to reduce acute pain, hasten rash healing and reduce the risk of PHN and other complications. Antiviral drugs are close to achieving these aims but do not entirely remove risk of PHN. Oral steroids show no protective effect against PHN. Adequate analgesia during the acute phase may require strong opioid drugs. Nerve blocks and tricyclic antidepressants (TCAs) may reduce the risk of PHN although firm evidence is lacking. PHN requires thorough evaluation and development of a management strategy for each individual patient. Initial therapy is with TCAs (e.g., nortriptyline) or the anticonvulsant gabapentin. Topical lidocaine patches frequently reduce allodynia. Strong opioids are sometimes required. Topical capsaicin cream is beneficial for a small proportion of patients but is poorly tolerated. NMDA antagonists have not proved beneficial with the exception of ketamine. Transcutaneous Electrical Nerve Stimulation (TENS) may be effective in some cases. HZ is a common condition. Severe complications such as stroke, encephalitis and myelitis are relatively rare whereas sight threatening complications of ophthalmic HZ are more common. PHN is common, distressing and often intractable. Good management improves outcome.

RANTES in onchocerciasis: changes with ivermectin treatment.

Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.

Phase II Study of Troxacitabine (BCH-4556) in Patients With Advanced and/or Metastatic Renal Cell Carcinoma: A Trial of the National Cancer Institute of Canada-Clinical Trials Group

A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.

Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy.

This article reviews the prevalence, risk factors, natural history, and impact on quality of life of painful diabetic neuropathy (PDN) and postherpetic neuralgia (PHN). Diabetes mellitus afflicts more than 14 million persons in the U.S. An estimated 20% to 24% of these persons experience PDN. Data on risk factors for PDN are limited, but duration of diabetes mellitus and poor glycemic control are probably important factors. Painful diabetic neuropathy may interfere with general activity, mood, mobility, work, social relations, sleep, leisure activities, and enjoyment of life. Herpes zoster strikes an estimated 800,000 persons each year in the U.S., most of whom are elderly or immunosuppressed. Using pain at 3 months after rash onset as a definition of PHN, between 25% and 50% of adults older than 50 years develop PHN, depending on early antiviral therapy for herpes zoster. Increasing age, greater pain and rash severity, greater degree of sensory impairment, and psychological distress are risk factors for PHN. Postherpetic neuralgia may cause fatigue, insomnia, depression, anxiety, interference with social roles and leisure activity, and impaired basic and instrumental activities of daily living. Both conditions are common complications of their underlying disorders and can profoundly diminish the quality of life of affected persons.

Rash severity in herpes zoster: Correlates and relationship to postherpetic neuralgia

Baseline and follow-up data from 4 samples of immunocompetent patients with herpes zoster who participated in clinical trials of the antiviral agent famciclovir were examined (N = 1778). In both univariate and multivariate analyses, severe rash (ie, >50 lesions, defined as papules, vesicles, or crusted vesicles) was significantly associated with older age, male sex, severe pain, primary involvement of nontrigeminal dermatomes, and a greater number of affected dermatomes. In addition, severe rash predicted the presence of pain 3 months later. The results indicate that severe rash is more common in patients with herpes zoster who are older and who have more severe acute pain and confirm that severe rash is a risk factor for prolonged pain. (J Am Acad Dermatol 2002;46:834-9.)

A noninvasive method to assess skin irritation and compromised skin conditions using simple tape adsorption of molecular markers of inflammation

We have developed a simple noninvasive method to assess inflammatory changes in human skin, even in the absence of visible clinical irritation. Our approach is based on a simple tape (Sebutape) adsorption method to recover molecular mediators of skin inflammation (e.g., cytokines). This procedure has been used to investigate baseline cytokine levels on skin, to assess normal skin condition and to evaluate changes due to chemical insult, existing dermatitis, or sun exposure. In clinical studies, Sebutape was applied to normal appearing uncompromised skin, as well as to compromised (diaper or heat rash), chemically treated (sodium laurel sulfate), or sun-exposed skin. Sebutape was applied to the skin for a 1 min collection interval. Tapes were extracted in saline using a 10 min sonication, and the extracts were analyzed for human interleukin-1alpha (IL-1alpha), IL-1 receptor antagonist (IL-1RA) and IL-8 using commercial immunoassay test kits. The cytokine levels recovered from each tape extract were normalized to total protein (TP) levels. In infant product use tests, the severity of skin irritation (diaper and heat rash or erythema) was also assessed using a visual grading scale. The method itself caused minimal, if any, skin damage. Additionally, Sebutape was shown to quantitatively adsorb detectable levels of cytokine from normal-appearing (control) or compromised (e.g., rashed or chemically treated) skin. In infant studies, significant increases in IL-1alpha levels were found in skin exhibiting diaper rash, heat rash and erythema compared with normal appearing control skin sites. When these results were normalized to total protein levels recovered from each tape, the significance was maintained. A positive correlation (r2=0.82) existed between IL-1RA levels and diaper rash severity. Significant increases in IL-8 levels were recovered from diaper rash versus control skin sites. There were differences in baseline cytokine levels in normal skin related to body site and sun exposure. The IL-1 RA/IL-1alpha ratios for sun-exposed skin of the face and lower leg were significantly (P<0.05) higher (3-6-fold) than those for skin sites that typically receive minimal sun exposure (i.e., underarm, upper leg and upper back). There was a significant increase in IL-1alpha and a directional increase in IL-8 levels in adult skin sites treated with the irritant, sodium lauryl sulfate, even in the absence of visible skin irritation (erythema). Our results demonstrate that this method is a useful noninvasive technique for assessing skin inflammatory events. In addition, the method is simple and easily applied in a clinical setting, whether on infants or adults.

Acute pain in herpes zoster: the famciclovir database project

The results of a considerable number of recent prospective studies have demonstrated that greater acute pain severity in herpes zoster patients is associated with a significantly greater risk of developing postherpetic neuralgia (PHN). Only a few studies have examined the relationships between acute pain severity and demographic characteristics and clinical features of patients with herpes zoster, however, and the results of these studies have been inconsistent. To clarify these relationships, data from 1778 herpes zoster patients studied within 72 h of rash onset in four clinical trials of the antiviral agent famciclovir were examined. Univariate and multivariate analyses indicated that greater acute pain severity was significantly associated with greater age, female sex, greater rash severity, the presence of a prodrome, and primary involvement of non-trigeminal dermatomes. These results demonstrate that three of the established risk factors for PHN – older age, greater rash severity, and the presence of a prodrome – are also associated with more severe acute pain assessed soon after rash onset in patients with herpes zoster. The results of this study are consistent with the recommendation that herpes zoster patients who are older, who have had a prodrome, or who have severe rash or severe acute pain should be targeted for interventions designed to prevent PHN.

Risk and prognostic factors of postherpetic neuralgia and focal sensory denervation: a prospective evaluation in acute herpes zoster ophthalmicus.

To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. A prospective clinical study. An ophthalmic practice participating in an eye-care network. A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.

Nontypical Henoch-Sch??nlein Purpura

To the Editor: The observation by A. Hakim (1) of four patients who had atypical skin rash is interesting. There are some similarities in those patients to the ones we described previously (2). There are also differences. The features which are similar are recurrent abdominal pain which was severe enough to cause crying and require a surgical consult. In contrast to our patients, however, all of the four patients described by Hakim had a rash. The rash was described as atypical. If the skin rash in Henoch-Schönlein purpura (HSP) is atypical, a skin biopsy should be done to look for the classic leukocytoclastic vasculitis. If such an examination was done, it was not reported by the authors. A rash in Henoch-Schönlein purpura is not always the presenting manifestation and as Hakim has stated, the rash may not be typical. Physicians understand the challenge in diagnosing HSP in patients in the absence of a rash. Our report and others have raised awareness of HSP in certain clinical situations and have suggested modalities for making an appropriate diagnosis. The dictum we learned from our patients is that if we have a young child with colicky abdominal pain of 1 to 2 weeks duration and there is no surgical cause think of HSP, particularly if the stools are positive for occult blood. In that situation, an upper GI endoscopy is helpful and may show the typical findings of HSP. Colonoscopy may also aid in the diagnosis. Regarding the etiology, prodromal viral illness has been described as an etiology of HSP. Though there is a higher occurrence of HSP in the late fall and spring, some patients are seen throughout the year. The observation of Hakim about the high incidence during winter may also suggest a specific viral etiology leading to the vasculitis. To use different ways of writing HSP reflecting the severity of the skin rash is interesting. Hakim is proposing that we use HSP if it is with a typical rash, HSp if it is with an atypical rash. We add that we use HSP-P (HSP minus P) if there is no rash in this condition. T. S. Gunasekaran M.D. James Berman M.D.

Continuous Topical Administration of a Petrolatum Formulation by a Novel Disposable Diaper

Background: Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have developed a novel diaper to deliver to the skin dermatological formulations intended to help protect the skin from overhydration and irritation. Objective: To determine the clinical benefits of a novel disposable diaper designed to deliver a petrolatum-based formulation continuously to the skin during use. Methods: Two independent, blinded, randomized clinical trials were conducted, involving an aggregate total of 391 children, 8–24 months of age. All comparisons were done versus a control diaper, identical to the test product except for the absence of the petrolatum formulation. The studies determined the effects of the novel diaper on skin erythema and diaper rash. Results: Use of the formulation-treated diaper was associated with significant reductions in severity of erythema and diaper rash compared to the control product. Conclusions: The results demonstrated the clinical benefits associated with continuous topical administration of a petrolatum-based formulation by this novel diaper. We anticipate that this advance in diaper design will contribute significantly to further reduce the prevalence and severity of irritant contact dermatitis in the diaper area.

The lifetime occurrence of Herpes zoster and prevalence of post-herpetic neuralgia: A retrospective survey in an elderly population

One-thousand-and-seventy-one randomly chosen elderly persons (537 women, 534 men; median age 80) were recruited from the Institute of Human Aging (Dept of Psychiatry, University of Liverpool). Almost a quarter (23.8%; equal numbers of both sexes) had had shingles (HZ), at a median age of 60 (for both sexes); 39 subjects (3.6% of all respondents, 15% of those who had had shingles), two thirds of whom were female, developed post-herpetic neuralgia (PHN), defined as pain persisting for more than 3 months; they acquired HZ at a median age of 70. In 22 of them, pain had resolved by the time they were questioned, but in 17 it was ongoing (from less than 12 to 504 months). Two new independent risk factors for PHN were identified: (1) female gender; and (2) living alone at the time of HZ acquisition ( p = 0.009). In addition to confirming the well-known factor of: (3) age at shingles acquisition (up to the early 90s); and (4) scarring, presumed to be a consequence of rash severity, was significantly commoner in subjects whose HZ was followed by PHN. Extrapolating the prevalence figures to the whole UK population, of whom 9.28 million were over 64 in 1992, it can be conservatively estimated that at any one time, some 200 000 people in the UK have PHN.