Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

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Methotrexate does not impede the development of contact allergy

Possible role of regional variation in allergic contact dermatitis: case report

Photo-contact allergy to octocrylene: a decreasing trend?

Issue Information

Allergic contact dermatitis caused by topical ketoconazole: a relevant issue? Review of ketoconazole-positive patch tests

Allergic contact dermatitis resulting from cetyl PEG/PPG-10/1 dimethicone in a deodorant cream

Vulvar oedema

Lymphomatoid contact dermatitis caused by limonene hydroperoxides confirmed by an exposure provocation test with the involved personal hygiene products

Spiramycin-related cutaneous eruption confirmed by patch testing

Propositional anaphors

Abstract

Propositions are posited to perform a variety of explanatory roles. One important role is being what is designated by a dedicated linguistic expression like a that-clause. In this paper, the case that propositions are needed for such a role is bolstered by defending that there are other expressions dedicated to designating propositions. In particular, it is shown that natural language has anaphors for propositions. Complement so and the response markers yes and no are argued to be such expressions.

Does needle biopsy cause an increased risk of extracapsular extension in the diagnosis of metastatic lymph node in melanoma?

Abstract

Background

Needle biopsy is a rapid, reliable, and reproducible procedure for histological confirmation of metastatic melanoma localization. Nonetheless, this procedure presents a theoretical risk of a mechanical weakening of the lymph node capsule with perinodal tumor seeding. The objective of the study was to evaluate the incidence of extracapsular extension after needle biopsy in comparison with surgical adenectomy in patients suspected of metastatic lymph node of melanoma.

Methods

We conducted a retrospective study of 1056 patients who underwent lymphadenectomy for melanoma between 2000 and 2016 in our unit. Sixty-nine patients were clinically and/or radiologically suspected of metastatic lymph node of melanoma. Patients were divided according to external lymph node biopsy or surgical adenectomy before lymphadenectomy. The primary endpoint was the histopathological identification of extracapsular extension in analyzed lymph nodes.

Results

The two populations were comparable except for the mitotic index, which was more frequently > 1/mm² in the group with surgical adenectomy (P = 0.005). The proportion of extracapsular extension was significantly greater in the needle biopsy group (28/37) than in patients who underwent surgical adenectomy (14/32) (P = 0.0067; OR = 4 [95% CI: 1.4–11]).

Conclusion

Our results suggest an increased risk of extracapsular extension after external lymph node biopsy in cases of suspicion of metastatic lymph node of melanoma. Thus, this encourages us to prefer surgical adenectomy in patients with suspected adenopathy accessible surgically. In other cases, needle biopsy should be carried out under radiological guidance using devices limiting tumor seeding.

Issue Information - TOC

Erratum

Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN)

Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma

Abstract

Background

This two-stage, phase IIa study (ClinicalTrials.gov: NCT01685008) investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin's lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells.

Patients and methods

Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary endpoint was overall response rate.

Results

Ninety-two patients were enrolled: DLBCL (n=35), FL (n=34), other iNHL (n=11) and MCL (n=12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (IRRs; 12%) and neutropenia (12%). One patient experienced a grade 4 IRR and eight patients (9%) grade 3/4 neutropenia. No treatment-related deaths were reported.

Conclusions

MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL.

ClinicalTrials.gov number

NCT01685008

Colchicine in dermatology: A review

Abstract

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

Dystrophic calcinosis cutis within burns, successfully treated with excision and secondary intention wound healing

Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells

Abstract

Introduction

Maternal-fetal chimerism is miniscule, a testament to the integrity of the uteroplacental interface. The soundness of this border region is potentially altered through cesarean delivery of prior babies with uncertain consequences for the following pregnancies.

Methods

Using multicolor flow cytometry and quantitative PCR of non-inherited maternal antigens we performed a retrospective case control pilot study and formulated the null hypothesis that placental implantation over a prior uterine scar does not result in the presence of memory Treg (CD45RO+) in the fetus. We then performed a power calculation and performed a blinded, appropriately powered prospective case control study to test the null hypothesis.

Results

Fetuses born to mothers with prior uterine scar have a roughly five times higher maternal to fetal microchimerism when the placenta directly interacts with the uterine scar. Unlike exposure to antigens in adult life, in utero antigenic exposure induces tolerogenic (Treg) responses in fetuses and we here report the presence of fetal Treg with a memory phenotype (CD45RO+). However, we only find such CD45RO+ fetal Tregs when the placenta abuts the uterine scar (Risk Ratio = 5 [p < 0.05 CI:(1.448 to 17.27)]). These memory fetal Tregs are functionally highly suppressive compared to CD45RA-expressing fetal Tregs, and have specificity for non-inherited maternal antigens.

Conclusions

We found that uterine scars, in the case of our study these scars are from prior c-sections, fundamentally impair uterine integrity allowing for increased antigen exposure of the fetus; with our appropriately powered study we rejected the null hypothesis and accepted the alternative hypothesis that placental implantation over a prior uterine scar results in the presence of memory Treg (CD45RO+) in the fetus. Thus, our study demonstrates a previously unappreciated role for uterine integrity in limiting fetal antigenic exposure, a key element to avoid the formation of inappropriate tolerances by the fundamentally tolerogenic fetal immune system.

Placental implantation over a prior cesarian scar has consequences in the subsequent pregnancy. The number of Treg does not change but their phenotype of fetal Treg is now activated. Thus, a scar, if the placenta is in contact with it, is a breach of the uterine barrier with consequences in the fetal immune system.

Ethosuximide-induced Stevens–Johnson syndrome: Beneficial effect of early intervention with high-dose corticosteroid therapy

Abstract

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens–Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

Case of deep vein thrombosis in a patient with advanced malignant melanoma treated with dabrafenib and trametinib

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

Abstract

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.

Benign cephalic histiocytosis: A case with infiltration of CD1a-positive langerin-negative cells

Cutaneous infiltration of plasmacytoid dendritic cells and t regulatory cells in skin lesions of polymorphic light eruption

Abstract

Background

Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate anti-microbial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptative immunity in skin by their immunosoppressive capacity.

Objective

The aim of the present study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin.

Methods

Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4- mm punch biopsy was taken from the site of positive photoprovocation test reaction and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well.

Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4, BDCA2 and CD4FOXP3 positive cells over the total inflammatory infiltrate was assessed for each case.

Results

We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples, and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (p<0.05).

Compared to healthy controls, both epidermic and dermic BDCA2+ cells count was significantly higher in PLE patients (p<0.05).

Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (p<0.05).

The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (p<0.05). Relative percentages of cellular infiltrations confirmed these results.

Conclusions

D-PDCS and Tregs may play a significant role in the development of PLE and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with Cutaneous Lupus Erythematosus (CLE).

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Focal facial hyperhidrosis associated with internal carotid artery dissection successfully treated with botulinum toxin A

Abstract

Hyperhidrosis affects up to 3% of the population⁽¹⁾. Secondary hyperhidrosis may be associated with infections, malignancies, endocrine or neurological diseases⁽²⁾. We report the first case of localized hyperhidrosis associated to Pourfour du Petit syndrome secondary to internal carotid artery dissection successfully and safely treated with botulinum toxin.

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The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: Analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study)

Abstract

Background

Psychological aspect and quality of life should be considered in treating patients with psoriasis.

Objective

We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis.

Methods

The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1,260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the psoriatic arthritis (PsA) screening and evaluation (PASE), dermatology life quality index (DLQI), MOS 36-item short-form health survey (SF-36), work productivity and activity impairment questionnaire psoriasis (WPAI: PSO), and medication satisfaction questionnaire (MSQ).

Results

Patients with a DLQI score>5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA), and had higher PASE scores than patients with DLQI≤5 (n = 266). The group of patients with exposed lesions (n=871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n=389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment, and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental).

Conclusion

The presence of exposed lesions has a negative impact on quality of life, mental health, and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

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Dermoscopic Features of Tungiasis

Abstract

Tungiasis is a parasitic infection caused by the sand flea Tunga penetrans. Tungiasis is prevalent in rural Central and South America, the Caribbean and sub-Saharan Africa.¹ In some endemic areas, the overall infestation prevalence exceeds 50 percent, and it remains an important public health problem for poor communities.^1,2 In some cases, the eruptions can mimic viral warts, furuncles, abscesses and paronychia.¹ Dermoscopy is reported to be a useful tool for differentiating between these and tungiasis lesions.^3,4 Moreover, the majority of cases have multiple lesions, with the ectoparasites causing more than 50 lesions in a single individual in some cases,⁵ and dermoscopy can help find the lesions. Despite the clinical utility of dermoscopy, no reports have assessed the significance of each dermoscopic finding in tungiasis. Here we report a case of tungiasis and we review the dermoscopic findings of 11 lesions of the patient to reveal the characteristic findings.

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Psoriatic arthritis screening by the dermatologist: development and first validation of the “PURE-4 scale”

Abstract

Background

Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identifying patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice.

Objective

To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis.

Methods

After literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012-2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques.

Results

168 patients were recruited, of whom 9 were excluded for known PsA and 21 did not attend the rheumatologist consultation. Out of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained 4 independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged<50. A total score (the PURE-4) was computed (0-4 points) that demonstrated excellent discriminative power (AUC=87.6%; Sensitivity=85.7% and Specificity=83.6% at the threshold of ≥1/4 points), with no evidence for over-optimism in bootstrapped internal validation.

Conclusion

These findings demonstrate the good diagnostic properties of a new screening scale using only 4 easy-to-collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.

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Patients affected by Dent disease 2 could be predisposed to hidradenitis suppurativa

Abstract

Dent disease 2 (DD2) is a rare X-Linked disorder characterized by proximal tubule dysfunction. It is considered as mild variant of Lowe Syndrome (LS) and both conditions are secondary to OCRL1 gene mutations.¹ Mutations in this gene drastically reduce (<10%) inositol polyphosphate 5-phosphatase (OCRL1) activity.¹

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Rapid Improvement of Psoriasis in a Patient with Lung Cancer after Treatment with Erlotinib

Abstract

We report the case of a 48-year-old woman with a rapid improvement of her psoriasis after treatment with erlotinib.A metastasised non-small cell lung cancer (NSCLC) was diagnosed and the psoriasis treatment with ustekinumab was stopped which caused a flare up of her psoriasis.

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Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes

Abstract

Objective

Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated and the role of high ENO1 expression in keratinocytes was characterized.

Methods

ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyze the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and trans-epithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA).

Results

ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 co-localized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression.

Conclusion

We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

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The desert wormwood (Artemisia herba-alba) – From Arabian folk medicine to a source of green and effective nanoinsecticides against mosquito vectors

Publication date: Available online 11 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Al Thbiani Aziz, Mohammed Ali Alshehri, Chellasamy Panneerselvam, Kadarkarai Murugan, Subrata Trivedi, Jazem A. Mahyoub, Mo'awia Mukhtar Hassan, Filippo Maggi, Stefania Sut, Stefano Dall'Acqua, Angelo Canale, Giovanni Benelli
The development of eco-friendly and effective insecticides is crucial for public health worldwide. Herein, we focused on the desert wormwood (Artemisia herba-alba), a plant widely used in Arabian traditional medicine, as a source of green nanoinsecticides against mosquito vectors, as well as growth inhibitors to be employed against microbial pathogens. Ag nanoparticles (AgNPs) fabricated with the A. herba-alba extract were tested against Indian and Saudi Arabian strains of Anopheles, Aedes and Culex mosquitoes. The chemical profile of the A. herba-alba extract was determined by LC-DAD-MS and ¹H NMR studies. Then, AgNPs were studied using UV–vis spectroscopy, XRD, FTIR spectroscopy, TEM, and EDX analyses. Artemisia herba-alba-synthesized AgNPs showed high larvicidal toxicity against mosquitoes from both Indian and Saudi Arabian strains. LC50 of AgNPs against Indian strains was 9.76 μg/ml for An. stephensi, 10.70 μg/ml for Ae. aegypti and 11.43 for Cx. quinquefasciatus whereas against Saudi Arabian strains it was 33.58 μg/ml for Ae. aegypti and 38.06 μg/ml for Cx. pipiens. In adulticidal experiments, A. herba-alba extract showed LC50 ranging from 293.02 to 450 μg/ml, while AgNP LC50 ranged from 8.22 to 27.39 μg/ml. Further, low doses of the AgNPs inhibited the growth of selected microbial pathogens. Overall, A. herba-alba can be further considered as a source of phytochemicals, with special reference to saponins, for effective and prompt fabrication of AgNPs with relevant insecticidal and bactericidal activity against species of high public health importance.

Graphical abstract

Hard onset therapy for functional hypoadduction and presbylaryngis: our experience in 22 patients

Abstract

Objectives

The hard onset, also known as a hard attack, or glottal onset, is a technique of vocal production in which the vocal folds are adducted prior to exhalation and forced open to begin phonation. In this study, we assessed the short-term efficacy of voice therapy incorporating hard onset techniques for patients with functional hypoadduction and presbyphonia. Design: Prospective cohort study. Setting: Tertiary academic medical center. Participants: Twenty-two patients with functional hypoadduction who underwent voice therapy, including hard-onset therapy, for 3 months. Main outcome measures: Vocal function pre-therapy and 3 months post-therapy assessed objectively by quantitative aerodynamic and acoustic analysis and subjectively by vocal handicap index (VHI) and grade, roughness, breathiness, asthenia, strain (GRBAS) scale. Results: Voice quality as graded by the VHI and GRBAS were statistically significantly improved following voice therapy. Objective comparisons reflected improvement in fundamental frequency, jitter, shimmer, normalized noise energy, and maximal phonation time. Conclusions: Voice therapy, including hard onset therapy, improved vocal quality and performance by both subjective and objective measures in patients with functional hypoadduction/presbyphonia.

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