Biological treatment for bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP. Objective: To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies. Methods: Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies. Results: We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported. Conclusions: Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.

A Combination of Non-ablative Laser and Hyaluronic Acid Injectable for Postacne Scars: A Novel Treatment Protocol.

Background: Postacne facial scars are often associated with significant patient distress. Energy-based devices, including non-ablative lasers, are commonly used for the treatment of postacne scarring. There is relatively limited data regarding the combination of non-ablative lasers with hyaluronic acid injections for postacne scarring. Objective: We aimed to evaluate the efficacy of a non-ablative 1,540-nm erbium:glass laser combined with a hyaluronic acid injectable for the treatment of postacne scars. Methods: This was a retrospective analysis of 12 patients who underwent the full treatment protocol. A before and after blinded clinical evaluation was performed independently by two dermatologists and graded on a scale from 0 (indicating a worsening of scarring) to 4 (indicating a 76-100% improvement in scarring). Pain perception, adverse effects, and patient satisfaction were evaluated. Results: A mean correct blinded before and after evaluation by two dermatologists was 96 percent. Patients demonstrated mild to moderate improvement as assessed by a quartile scale of improvement (25-50%). Mild transient pain was reported by most patients. The satisfaction level of the patients was high (4 out of 5). Limitations: The limitations of our study include the small cohort, retrospective design, and lack of a histological correlation. Conclusion: Our results suggest that this combination treatment using 1,540-nm fractional erbium:glass laser and hyaluronic acid injections is both safe and effective for patients with postacne facial scars.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Treatment of Pemphigus with Rituximab: Real-Life Experience in a Cohort of 117 Patients in Israel.

BACKGROUND: A combined regimen of rituximab with corticosteroids for the treatment of pemphigus was effective in a prospective randomized controlled trial. OBJECTIVE: To assess real-life response to rituximab in patients with pemphigus. METHODS: A retrospective cohort of patients with pemphigus treated with ≥1 rituximab cycles (1,000 mg on days 0 and 14). The primary outcome was remission rate after 1 cycle. For efficacy analyses, a minimal 6-month follow-up was required. Adverse events were assessed in all patients. RESULTS: The cohort included 117 patients for safety analysis, 108 for efficacy analysis (median follow-up of 33 months). All but one received concomitant corticosteroids, a third also received adjuvants. Overall, 80/108 patients (74%) achieved remission after the first rituximab cycle at a median of 5.5 months. Relapses occurred in 39 patients (49%) at a median of 18 months. Repeating treatment in relapsed patients increased remission rates to 75 and 88% after the second and third cycles, respectively. Adverse events were similar to those of previous publications. Two elderly patients died of infections attributable to rituximab combined with high-dose corticosteroids. CONCLUSION: In a large real-life long-term cohort, rituximab with corticosteroids ± adjuvants induced remission in most patients with pemphigus, with relatively favorable safety. Repeating treatment following relapse or remission failure was beneficial.

Does interval time between pulsed dye laser treatments for port-wine stains influence outcome? A systematic review and meta-analysis.

The pulsed dye laser (PDL) is the standard treatment for port-wine stains (PWS). Maximal improvement occurs after multiple treatment sessions; however, the optimal treatment interval has yet to be determined. The aim of this study was to review whether there is an association between PDL treatment interval and outcome of PWS. Six databases were searched by three reviewers for publications investigating treatment of PWS with PDL. The 75% improvement rates (75IR) were extracted for quantitative analysis. Meta-regression was used to investigate the association between treatment intervals and 75IR. The systematic review included 1 RCT and 33 cohort studies (7 prospective cohorts and 26 retrospective cohorts), with a total of 3777 patients. The pooled 75IR was 37% (95% CI 29-45%; I2 = 95%). Light Fitzpatrick skin type (p = 0.04), facial anatomic location (p = 0.01), and young age (p = 0.008) were associated with 75IR. In an unadjusted (p = 0.42) and multivariable adjusted (p = 0.98) meta-regression, no association was found between time interval between treatments and 75IR. These results persisted in a sensitivity analysis of studies with a mean patient age of ≤ 1. The majority of included studies were heterogeneous and retrospective. Based on cohort studies of low-to-moderate quality, time intervals between PDL treatments are not associated with PWS outcome.

The role of technology in melanoma screening and diagnosis.

Melanoma presents challenges for timely and accurate diagnosis. Expert panels have issued risk-based screening guidelines, with recommended screening by visual inspection. To assess how recent technology can impact the risk/benefit considerations for melanoma screening, we comprehensively reviewed non-invasive visual-based technologies. Dermoscopy increases lesional diagnostic accuracy for both dermatologists and primary care providers; total body photography and sequential digital dermoscopic imaging also increase diagnostic accuracy, are supported by automated lesion detection and tracking, and may be best suited to use by dermatologists for longitudinal follow-up. Specialized imaging modalities using non-visible light technology have unproven benefit over dermoscopy and can be limited by cost, access, and training requirements. Mobile apps facilitate image capture and lesion tracking. Teledermatology has good concordance with face-to-face consultation and increases access, with increased accuracy using dermoscopy. Deep learning models can surpass dermatologist accuracy, but their clinical utility has yet to be demonstrated. Technology-aided diagnosis may change the calculus of screening; however, well-designed prospective trials are needed to assess the efficacy of these different technologies, alone and in combination to support refinement of guidelines for melanoma screening.

Treatment of Bullous Pemphigoid in People Aged 80 Years and Older: A Systematic Review of the Literature.

BACKGROUND: Bullous pemphigoid commonly affects older adults and has a detrimental effect on both quality of life and longevity. Systemic corticosteroids, the mainstay of therapy, may cause significant adverse effects, especially in older patients. Therefore, safer therapeutic options are being sought. OBJECTIVE: The objective of this article was to systematically review the published evidence on the efficacy and safety of different treatment modalities for bullous pemphigoid in older patients. METHODS: We performed a systematic review of all publications until May 2020 in PubMed, Google Scholar, and the ongoing trials registry of the US National Institutes of Health databases evaluating the efficacy and safety of bullous pemphigoid treatments in patients aged older than 80 years. The primary outcome was complete response. The secondary outcomes were partial response, complete remission on minimal therapy or during tapering, recurrence, adverse events, and mortality. RESULTS: Twenty-eight publications were included: 2 randomized controlled trials, 5 prospective cohort studies, 10 retrospective cohort studies, and 11 case series, with a total of 153 older patients. The overall complete response rate was 31%. Topical corticosteroids had the highest complete response rate (55%) with a low side-effect profile. Biologics (omalizumab and rituximab) were effective in achieving complete remission on minimal therapy (29%) without recurrence, although rituximab was associated with a relatively high mortality rate (29%). CONCLUSIONS: Current data suggest that topical corticosteroids are effective and safe and should remain the first line of treatment for bullous pemphigoid in older adults. However, their application is difficult and requires a high-functioning patient, third-party assistance, or a relatively mild disease. Biological agents are effective but warrant meticulous patient selection owing to the relatively high mortality rate associated with rituximab. CLINICAL TRIAL REGISTRATION: PROSPERO registration number CRD42020186686.

Outcomes and Risk Factors in Patients with Multiple Primary Melanomas.

The incidence and patient survival rates of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPMs). To determine risk factors for developing MPMs and compare the survival of patients with MPMs to those with single primary melanomas, a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6,963 patients with single primary melanomas and 305 patients with MPMs were identified. Mean follow-up was 8.3 ± 6.3 years for patients with single primary melanomas and 8.8 ± 5.9 years for patients with MPMs. Risk of developing multiple melanomas increased with age at diagnosis of first melanoma (hazard ratio [HR] = 1.20 for a 10-year increase in age, 95% confidence interval [CI] = 1.11-1.29, P < 0.001), male sex (HR = 1.44, 95% CI = 1.12-1.84, P = 0.005), and white race (HR = 3.07, 95% CI = 1.45-6.51). Patients with invasive MPMs had increased risk of melanoma-specific death both before (HR = 1.47, 95% CI = 1.0-2.2) and after adjusting for age, sex, site, race, family history of melanoma, personal history of other cancer, and Surveillance, Epidemiology, and End Results Program (SEER) stage (HR = 1.44, 95% CI = 0.95-2.2); however, this result did not reach statistical significance.

Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS-mutant and wild-type melanoma.

Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS-mutant and BRAFWT NRASWT metastatic melanoma. To target these pathways, NRAS-mutant and BRAFWT NRASWT patients received oral trametinib at 1.5 mg daily and GSK2141795 at 50 mg daily in a two-cohort Simon two-stage design. Participants had adequate end-organ function and no more than two prior treatment regimens. Imaging assessments were performed at 8-week intervals. A total of 10 NRAS-mutant and 10 BRAFWT NRASWT patients were enrolled. No objective responses were noted in either cohort. The median PFS and OS were 2.3 and 4.0 months in the NRAS-mutant cohort and 2.8 and 3.5 months in the wild-type cohort. Grade 3 and grade 4 adverse events, primarily rash, were observed in 25% of patients. We conclude that the combination of trametinib and GSK2141795 does not have significant clinical activity in NRAS-mutant or BRAFWT NRASWT melanoma.

All-cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: There are varying reports of the association of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) with mortality. OBJECTIVE: To synthesize the available information on all-cause mortality after a diagnosis of BCC or SCC in the general population. METHODS: We searched PubMed (1966-present), Web of Science (1898-present), and Embase (1947-present) and hand-searched to identify additional records. All English articles that reported all-cause mortality in patients with BCC or SCC were eligible. We excluded case reports, case series, and studies in subpopulations of patients. Random effects model meta-analyses were performed separately for BCC and SCC. RESULTS: The searches yielded 6538 articles, and 156 were assessed in a full-text review. Twelve studies met the inclusion criteria, and 4 were included in the meta-analysis (encompassing 464,230 patients with BCC and with 175,849 SCC), yielding summary relative mortalities of 0.92 (95% confidence interval, 0.83-1.02) in BCC and 1.25 (95% confidence interval, 1.17-1.32) in SCC. LIMITATIONS: Only a minority of studies controlled for comorbidities. There was significant heterogeneity in meta-analysis (χ2P < .001, I2 > 98%), but studies of SCC were qualitatively concordant: all showed statistically significant increased relative mortality. CONCLUSIONS: We found that patients with SCC are at higher risk for death from any cause compared with the general population.

Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy.

BACKGROUND: Programmed death 1 (PD-1) inhibition activates partially exhausted cytotoxic T lymphocytes (peCTLs) and induces tumor regression. We previously showed that the peCTL fraction predicts response to anti-PD-1 monotherapy. Here, we sought to correlate peCTL and regulatory T lymphocyte (Treg) levels with response to combination immunotherapy, and with demographic/disease characteristics, in metastatic melanoma patients. METHODS: Pretreatment melanoma samples underwent multiparameter flow cytometric analysis. Patients were treated with anti-PD-1 monotherapy or combination therapy, and responses determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria. peCTL and Treg levels across demographic/disease variables were compared. Low versus high peCTL (≤20% vs. >20%) were defined from a previous study. RESULTS: One hundred and two melanoma patients were identified. The peCTL fraction was higher in responders than nonresponders. Low peCTL correlated with female sex and liver metastasis, but not with lactate dehydrogenase (LDH), tumor stage, or age. While overall response rates (ORRs) to anti-PD-1 monotherapy and combination therapy were similar in high-peCTL patients, low-peCTL patients given combination therapy demonstrated higher ORRs than those who received monotherapy. Treg levels were not associated with these factors nor with response. CONCLUSION: In melanoma, pretreatment peCTL fraction is reduced in women and in patients with liver metastasis. In low-peCTL patients, anti-PD-1 combination therapy is associated with significantly higher ORR than anti-PD-1 monotherapy. Fewer tumor-infiltrating peCTLs may be required to achieve response to combination immunotherapy. TRIAL REGISTRATION: UCSF IRB Protocol 138510FUNDING. NIH DP2-AR068130, K08-AR062064, AR066821, and Burroughs Wellcome CAMS-1010934 (M.D.R.). Amoroso and Cook Fund, and the Parker Institute for Cancer Immunotherapy (A.I.D.).

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.

BACKGROUND: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy. METHODS: A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg-1 Q2W or Q3W) or nivolumab (3 mg kg-1 Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale. RESULTS: The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration. CONCLUSIONS: Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.

Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision.

Importance: Melanoma in situ (MIS) is increasing in incidence, and expert consensus opinion recommends surgical excision for therapeutic management. Currently, wide local excision (WLE) is the standard of care. However, Mohs micrographic surgery (MMS) is now used to treat a growing subset of individuals with MIS. During MMS, unlike WLE, the entire cutaneous surgical margin is evaluated intraoperatively for tumor cells. Objective: To assess the outcomes of patients with MIS treated with MMS compared with those treated with WLE. Design, Setting, and Participants: Retrospective review of a prospective database. The study cohort consisted of 662 patients with MIS treated with MMS or WLE per standard of care in dermatology and surgery (general surgery, otolaryngology, plastics, oculoplastics, surgical oncology) at an academic tertiary care referral center from January 1, 1978, to December 31, 2013, with follow-up through 2015. Exposure: Mohs micrographic surgery or WLE. Main Outcomes and Measures: Recurrence, overall survival, and melanoma-specific survival. Results: There were 277 patients treated with MMS (mean [SD] age, 64.0 [13.1] years; 62.1% male) and 385 treated with WLE (mean [SD] age, 58.5 [15.6] years; P < .001 for age; 54.8% male). Median follow-up was 8.6 (range, 0.2-37) years. Compared with WLE, MMS was used more frequently on the face (222 [80.2%] vs 141 [36.7%]) and scalp and neck (23 [8.3%] vs 26 [6.8%]; P < .001). The median (range) year of diagnosis was 2008 (1986-2013) for the MMS group vs 2003 (1978-2013) for the WLE group (P < .001). Overall recurrence rates were 5 (1.8%) in the MMS group and 22 (5.7%) in the WLE group (P = .07). Mean (SD) time to recurrence after MMS was 3.91 (4.4) years, and after WLE, 4.45 (2.7) years (P = .73). The 5-year recurrence rate was 1.1% in the MMS group and 4.1% in the WLE group (P = .07). For WLE-treated tumors, the surgical margin taken was greater for tumors that recurred compared with tumors that did not recur (P = .003). Five-year overall survival for MMS was 92% and for WLE was 94% (P = .28). Melanoma-specific mortality for the MMS group was 2 vs 13 patients for the WLE group, with mean (SD) survival of 6.5 (4.8) and 6.1 (0.8) years, respectively (P = .77). Conclusions and Relevance: No significant differences were found in the recurrence rate, overall survival, or melanoma-specific survival of patients with MIS treated with MMS compared with WLE.

Dietary modifications in atopic dermatitis: patient-reported outcomes.

BACKGROUND: Patients with atopic dermatitis (AD) commonly turn to dietary modifications to manage their skin condition. OBJECTIVES: To investigate patient-reported outcomes and perceptions regarding the role of diet in AD. METHODS: One hundred and sixty nine AD patients were surveyed in this cross-sectional study. The 61-question survey asked about dietary modifications, perceptions and outcomes. RESULTS: Eighty seven percent of participants reported a trial of dietary exclusion. The most common were junk foods (68%), dairy (49.7%) and gluten (49%). The best improvement in skin was reported when removing white flour products (37 of 69, 53.6%), gluten (37 of 72, 51.4%) and nightshades (18 of 35, 51.4%). 79.9% of participants reported adding items to their diet. The most common were vegetables (62.2%), fish oil (59.3%) and fruits (57.8%). The best improvement in skin was noted when adding vegetables (40 of 84, 47.6%), organic foods (17 of 43, 39.5%) and fish oil (28 of 80, 35%). Although 93.5% of patients believed it was important that physicians discuss with them the role of diet in managing skin disease, only 32.5% had consulted their dermatologist. CONCLUSIONS: Since dietary modifications are extremely common, the role of diet in AD and potential nutritional benefits and risks need to be properly discussed with patients.

Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma.

BACKGROUND: Immune checkpoint blockade is revolutionizing therapy for advanced cancer, but many patients do not respond to treatment. The identification of robust biomarkers that predict clinical response to specific checkpoint inhibitors is critical in order to stratify patients and to rationally select combinations in the context of an expanding array of therapeutic options. METHODS: We performed multiparameter flow cytometry on freshly isolated metastatic melanoma samples from 2 cohorts of 20 patients each prior to treatment and correlated the subsequent clinical response with the tumor immune phenotype. RESULTS: Increasing fractions of programmed cell death 1 high/cytotoxic T lymphocyte-associated protein 4 high (PD-1hiCTLA-4hi) cells within the tumor-infiltrating CD8+ T cell subset strongly correlated with response to therapy (RR) and progression-free survival (PFS). Functional analysis of these cells revealed a partially exhausted T cell phenotype. Assessment of metastatic lesions during anti-PD-1 therapy demonstrated a release of T cell exhaustion, as measured by an accumulation of highly activated CD8+ T cells within tumors, with no effect on Tregs. CONCLUSIONS: Our data suggest that the relative abundance of partially exhausted tumor-infiltrating CD8+ T cells predicts response to anti-PD-1 therapy. This information can be used to appropriately select patients with a high likelihood of achieving a clinical response to PD-1 pathway inhibition. FUNDING: This work was funded by a generous gift provided by Inga-Lill and David Amoroso as well as a generous gift provided by Stephen Juelsgaard and Lori Cook.

Sex disparities in melanoma outcomes: the role of biology.

Melanoma outcomes differ between men and women even when adjusted for prognostic factors such as age, Breslow thickness, body site, ulceration, lymph node dissection, and for treatment, with men having poorer outcomes compared to women. The mechanisms underlying this disparity are not well understood. Behavioral differences between the sexes such as ultraviolet light exposure and health care services utilization have been suggested as contributing, and differences in endogenous biological processes such as immune function, hormonal regulation, oxidative stress response, vitamin D metabolism and sex chromosome gene expression have also been proposed as mechanisms. This review examines the cumulative evidence for biologically based processes that lead to differences in melanoma biology, including inherent sex-based differences in immune function, oxidative stress response and vitamin D metabolism; the complex interplay between sex hormones, the immune system and oxidative stress response; the effect of non-random X chromosome inactivation on tumorigenesis; and the potential contribution of recently identified oncogenes on the Y chromosome.

Diagnostic markers of serious bacterial infections in febrile infants younger than 90 days old.

BACKGROUND: The aim of this study was to assess correlations between demographic, clinical and laboratory characteristics and the risk of serious bacterial infection (SBI) in febrile <90-day-old infants. METHODS: Medical records of all infants younger than 90 days old hospitalized at Dana-Dwek Children's Hospital (2006-2008) for evaluation of fever were retrospectively reviewed. Data on clinical, laboratory and demographic characteristics were retrieved and evaluated. RESULTS: Forty-eight of the 401 study infants (12%) had SBI: most of them had urinary tract infection (43 infants; 90% of all SBI), three infants had bacteremia, one had bacterial pneumonia and one had bacterial meningitis. Significant independent clinical predictors for the diagnosis of SBI included duration of fever, absence of rhinitis and the absence of lung and skin manifestations. Significant independent laboratory predictors were absolute neutrophil count (ANC), platelets, blood urea nitrogen and C-reactive protein (CRP) level. On receiver operating characteristic curve analysis, the CRP area under the curve (0.819) was significantly superior to ANC and leukocyte count. CONCLUSION: Of the clinical and laboratory variables selected for evaluation, qualitative CRP was the strongest independent predictor for diagnosing SBI and a significantly better diagnostic marker than clinical characteristics, ANC and white blood cell count.