Challenges in the Diagnosis of Cutaneous Mastocytosis.

BACKGROUND: Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult. METHODS: This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM). RESULTS: The nomenclature of the term "CM" is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier's sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement. CONCLUSIONS: Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course.

Enabling precision monitoring of psoriasis treatment by optoacoustic mesoscopy.

Psoriasis is a widespread inflammatory skin disease affecting about 2% of the general population. Recently, treatments that specifically target key proinflammatory cytokines driving the disease have been developed to complement conventional therapies with unspecific antiproliferative or anti-inflammatory effects. Efficient monitoring of treatment efficacy in the context of precision medicine and the assessment of new therapeutics require accurate noninvasive readouts of disease progression. However, characterization of psoriasis treatment remains subjective based on visual and palpatory clinical assessment of features observed on the skin surface. We hypothesized that optoacoustic (photoacoustic) mesoscopy could offer label-free assessment of inflammation biomarkers, extracted from three-dimensional (3D) high-resolution images of the human skin, not attainable by other noninvasive methods. We developed a second-generation ultra-broadband optoacoustic mesoscopy system, featuring sub-10-µm resolution and advanced motion correction technology, and performed 80 longitudinal measurements of 20 psoriatic skin plaques in humans under conventional inpatient treatment or receiving biologics with concomitant topical corticosteroid treatment. Optoacoustic image analysis revealed inflammatory and morphological skin features that indicated treatment efficacy with sensitivity, accuracy, and precision that was not possible using clinical metrics. We identify 3D imaging biomarkers that reveal responses to treatment and offer the potential to facilitate disease and treatment characterization. Our findings suggest that optoacoustic mesoscopy may offer a method of choice for yielding both qualitative and quantitative evaluations of skin treatments that are inaccessible by other methods, potentially enabling optimized therapies and precision medicine in dermatology.

Fast raster-scan optoacoustic mesoscopy enables assessment of human melanoma microvasculature in vivo.

Melanoma is associated with angiogenesis and vascular changes that may extend through the entire skin depth. Three-dimensional imaging of vascular characteristics in skin lesions could therefore allow diagnostic insights not available by conventional visual inspection. Raster-scan optoacoustic mesoscopy (RSOM) images microvasculature through the entire skin depth with resolutions of tens of micrometers; however, current RSOM implementations are too slow to overcome the strong breathing motions on the upper torso where melanoma lesions commonly occur. To enable high-resolution imaging of melanoma vasculature in humans, we accelerate RSOM scanning using an illumination scheme that is coaxial with a high-sensitivity ultrasound detector path, yielding 15 s single-breath-hold scans that minimize motion artifacts. We apply this Fast RSOM to image 10 melanomas and 10 benign nevi in vivo, showing marked differences between malignant and benign lesions, supporting the possibility to use biomarkers extracted from RSOM imaging of vasculature for lesion characterization to improve diagnostics.

Health-Related Quality of Life and Influencing Factors in Adults with Nonadvanced Mastocytosis-A Cross-Sectional Study and Qualitative Approach.

BACKGROUND: Mastocytosis comprises a heterogeneous group of disorders characterized by an accumulation of mast cells in 1 or more organs. Symptoms range from mild complaints to severe and life-threatening events. Impact on quality of life seems to vary widely, but influencing factors are poorly understood so far. OBJECTIVE: To examine impairments, psychological burden, health-related quality of life (HRQOL), and possible influencing factors in patients with mastocytosis. METHODS: In semistructured telephone interviews, patients provided information on impairments in everyday life and psychological burden caused by mastocytosis. HRQOL was measured using the Mastocytosis Quality of Life (MC-QoL) questionnaire. Clinical data were collected from patient files. RESULTS: A total of 101 adult patients with mastocytosis (74.3% women; mean age, 47.7 ± 13.5 years) were included. Half of the interviewed patients (50.6%) reported disease-related impairments in everyday life, and 42.4% stated a psychological burden. MC-QoL questionnaire scores showed a broad distribution, with a mean total score at a "mild" impairment level (mean total score, 34.7 ± 22.5). One-third of patients felt moderately (22.8%) or severely (13.9%) impaired, whereas one-third reported no impairment at all (30.7%). Symptoms of mast cell activation and perceived food intolerance had the highest impact on HRQOL. Higher age, higher body mass index, higher tryptase level, and longer duration of symptoms, as well as current drug therapy and pathological bone density, were each associated with reduced HRQOL. CONCLUSIONS: A high level of suffering and strong associations between impairments and symptom-related factors indicate the importance of addressing patients' concerns and adequate symptom management in mastocytosis.

Optoacoustic mesoscopy shows potential to increase accuracy of allergy patch testing.

BACKGROUND: Differentiation between irritant and allergic skin reactions in epicutaneous patch testing is based largely on subjective clinical criteria, with the risk of high intraobserver and interobserver variability. Novel dermatological imaging using optoacoustic mesoscopy allows quantitative three-dimensional assessment of microvascular biomarkers. OBJECTIVES: We investigated the potential of optoacoustic imaging to improve the precision of patch test evaluation. METHODS: Sixty-nine test reactions and 48 healthy skin sections in 52 patients with suspected type IV allergy were examined using raster-scan optoacoustic mesoscopy. RESULTS: We identified biomarkers from the optoacoustic images. Allergic reactions were associated with higher fragmentation of skin vasculature than irritant reactions (19.5 ± 9.7 vs 14.3 ± 3.7 fragments/100 pixels2 ; P < .05), as well as lower ratio of low- to high-frequency acoustic signals (1.6 ± 0.5 vs 2.0 ± 0.6, P < .05). Allergic reactions graded "++" showed higher vessel fragmentation than reactions graded "+" (25.4 ± 13.2 vs 17.1 ± 6.5 fragments/100 pixels2 ; P < .05). A linear model combining the biomarkers fragmentation and frequency ratio could differentiate allergic from irritant test reactions with an area under the receiving operator characteristic curve of 0.80 (95% confidence interval 0.64-0.91), reaching a sensitivity of 81% and specificity of 63%. CONCLUSIONS: Optoacoustic mesoscopy shows potential to help in differentiating between allergic and irritant test reactions based on novel biomarkers that may reflect vasodilation, vessel tortuosity, and edema.

Optical features of human skin revealed by optoacoustic mesoscopy in the visible and short-wave infrared regions.

Detailed assessment of skin conditions or the efficacy of skin treatments could greatly benefit from noninvasively assessing the distribution of cutaneous and subcutaneous structures and biomolecules. We considered ultrawideband raster scan optoacoustic mesoscopy with an extended wavelength range from visible to short-wave infrared and observed previously unseen high-resolution images of lipids colocalized with water, melanin, and hemoglobin distribution in human skin. Based on this contrast, the technique resolves subcutaneous fat, the pilosebaceous unit with complete hair strand and bulb, dermal microvasculature, and epidermal structures. We further visualize melanoidins that form via the Maillard reaction in the ultrathin stratum corneum layer, analyze their absorption spectrum, and separate them from the melanin layer. The suggested method may allow novel interrogation of skin conditions, possibly impacting diagnostics and medical and cosmetic treatments.

Motion Quantification and Automated Correction in Clinical RSOM.

Raster-scan optoacoustic mesoscopy (RSOM) offers high-resolution non-invasive insights into skin pathophysiology, which holds promise for disease diagnosis and monitoring in dermatology and other fields. However, RSOM is quite vulnerable to vertical motion of the skin, which can depend on the part of the body being imaged. Motion correction algorithms have already been proposed, but they are not fully automated, they depend on anatomical segmentation pre-processing steps that might not be performed successfully, and they are not site- specific. Here, we determined for the first time the magnitude of the micrometric vertical skin displacements at different sites on the body that affect RSOM. The quantifi- cation of motion allowed us to develop a site-specific correction algorithm. The algorithm is fully automated and does not need prior anatomical information. We found that the magnitude of the vertical motion depends strongly on the site of imaging and is caused by breathing, heart beating, and arterial pulsation. The developed algorithm resulted in more than 2-fold improvement in the signal-to-noise ratio of the reconstructed images at every site tested. Proposing an effective automated motion correction algorithm paves the way for realizing the full clinical potential of RSOM.

Prevalence and Risk Factors for Hearing Loss in Chilean Shellfish Divers.

BACKGROUND: Diving within artisanal fishing is a profession carried out by many men in coastal communities of southern Chile. These shellfish divers use surface supplied air for breathing. Among potential health threats are occupational accidents, decompression sickness and barotrauma. Repeated middle and inner ear barotrauma and decompression sickness of the ear may result in hearing loss. OBJECTIVE: To determine the prevalence of hearing loss and related risk factors in artisanal shellfish divers. METHODS: A cross-sectional study including 125 male shellfish divers was carried out in a coastal village in southern Chile. Participants were interviewed using a standard Spanish questionnaire adapted for this population. Hearing loss was assessed through audiometry. Any hearing loss, sensorineural hearing loss and other types of hearing loss (conduction, unilateral and mixed) were used as the outcomes. Bivariate and multiple logistic regression models were carried out to identify risk factors for hearing loss. FINDINGS: Median duration on the job was 25 years (range 1-52), 64% of divers had a low level of schooling and 52% reported not knowing how to use decompression tables. Most (86%) of the divers dove deeper than 30 meters exceeding the 20 meters permitted by law. The majority (80%) reported having experienced several episodes of type II decompression sickness during their working life. The prevalence of any type of hearing loss was 54.4%: 29.0% presented sensorineural hearing loss and 25.6% presented other types of hearing impairment. After adjustment for age and other potential risk factors, diving more than 25 years was the main predictor for all kinds of hearing loss under study. CONCLUSIONS: Hearing loss is frequent in artisanal shellfish divers and safety measures are limited. Although based on small numbers and lacking an unexposed comparison group, our results suggest the need for community-based interventions.