Non-invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

BACKGROUND: Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. OBJECTIVES: To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. METHODS: We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. RESULTS: The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. CONCLUSIONS: With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned.

Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone.

BACKGROUND: The group of autoinflammatory syndromes associated with Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis are poorly defined and difficult to control with currently available treatment modalities. OBJECTIVES: We describe a patient with PASH syndrome and report about the successful multimodal treatment with infliximab, cyclosporine, and dapsone. METHODS: A review of the available literature to date about this group of autoinflammatory diseases was performed. We performed genetic analysis for PSTPIP1 mutations associated with PAPA syndrome. RESULTS: A 22-year-old woman presented to our department with pyoderma gangrenosum, concomitant acne, and suppurative hidradenitis. She had previously been treated unsuccessfully with etanercept, adalimumab, fumaric acid and the IL-1 receptor antagonist (IL-1RA) anakinra without prolonged remission. Treatment with intravenous infliximab in combination with cyclosporine and dapsone lead to sudden and prolonged improvement of the clinical symptoms that we classified as PASH syndrome. We review the literature about this group of diseases and report the third case of PASH syndrome to date. CONCLUSION: PASH syndrome and associated diseases should be considered whenever hidradenitis suppurativa is found in association with pyoderma gangrenosum. We provide a systematic overview about PASH syndrome and suggest a novel multimodal therapeutic regimen beyond isolated inhibition of TNF or IL-1.

Schnitzler's syndrome: diagnosis, treatment, and follow-up.

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended.

Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases.

BACKGROUND: The clinical diagnosis of amelanotic melanoma is often challenging, because the classical clinical and dermoscopic features of pigmented melanoma are usually missing. The reflectance confocal microscopy (RCM) offers an additional possibility of an in vivo diagnosis of both pigmented and amelanotic melanoma lesions. OBJECTIVES: To test the value of RCM in vivo in the preoperative prediction of melanoma lesions lacking significant pigment and to compare the results with the evaluation by dermoscopy and histopathology. METHODS: We examined seven patients with the clinically uncertain differential diagnosis of partially or completely amelanotic melanoma by RCM and dermoscopy prior to surgical excision of the lesions according to the previously suggested dermoscopy algorithm and RCM score for melanoma. The following RCM features were evaluated: major criteria scored +2 (non-edged papillae, cytological atypia at the dermo-epidermal junction) and minor criteria +1 (roundish pagetoid cells, widespread pagetoid infiltration, nucleated cells within dermal papillae, cerebriform cell clusters). The dermoscopic evaluation included the following criteria: polymorphous vessels, dotted and linear irregular vessels, hairpin vessels, pink-erythematous colour, milky red areas, irregularly shaped depigmentation, blue-grey dots and subtle pigmentation. RESULTS: The preoperative in vivo RCM analysis revealed common features of melanoma also found in pigmented melanoma lesions. All lesions showed a score above three in the applied RCM algorithm which was proposed earlier as the threshold for malignancy. In dermoscopy, five of seven lesions showed characteristic vascular changes. CONCLUSION: In vivo RCM is a valuable tool in the preoperative diagnosis of partially and completely amelanotic tumours suspicious for melanoma in addition to dermoscopic evaluation.

Morphology of basal cell carcinoma in high definition optical coherence tomography: en-face and slice imaging mode, and comparison with histology.

BACKGROUND: Optical coherence tomography (OCT) allows real-time, in vivo examination of basal cell carcinoma (BCC). A new high definition OCT with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of BCC and may potentially replace invasive diagnostic biopsies. OBJECTIVES: To define the characteristic morphologic features of BCC by using high definition optical coherence tomography (HD-OCT) compared to conventional histology. METHODS: A total of 22 BCCs were examined preoperatively by HD-OCT in the en-face and slice imaging mode and characteristic features were evaluated in comparison to the histopathological findings. RESULTS: The following features were found in the en-face mode of HD-OCT: lobulated nodules (20/22), peripheral rimming (17/22), epidermal disarray (21/22), dilated vessels (11/22) and variably refractile stroma (19/22). In the slice imaging mode the following characteristics were found: grey/dark oval structures (18/22), peripheral rimming (13/22), destruction of layering (22/22), dilated vessels (7/22) and peritumoural bright stroma (11/22). In the en-face mode the lobulated structure of the BCC was more distinct than in the slice mode compared to histology. CONCLUSION: HD-OCT with a horizontal and vertical imaging mode offers additional information in the diagnosis of BCC compared to conventional OCT imaging and enhances the feasibility of non-invasive diagnostics of BCC.

Actinic keratosis in the en-face and slice imaging mode of high-definition optical coherence tomography and comparison with histology.

BACKGROUND: Optical coherence tomography (OCT) allows real-time, in vivo examination of nonmelanoma skin cancer. An innovative high-definition (HD)-OCT with a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of actinic keratosis (AK) and may potentially replace invasive diagnostic biopsies. OBJECTIVES: To define the characteristic morphological features of AK by using HD-OCT in the two imaging modes compared with histopathology as gold standard. METHODS: In total, 20 AKs were examined by HD-OCT in the en-face and slice imaging modes and characteristic features were described and evaluated in comparison with the histopathological findings. Furthermore, the HD-OCT images of a subgroup of AKs were compared with those of the clinically normal adjacent skin. RESULTS: The preoperative in vivo diagnostics showed the following features in the en-face imaging mode of HD-OCT: disruption of stratum corneum, architectural disarray, cellular/nuclear polymorphism in the stratum granulosum/stratum spinosum, and bright irregular bundles in the superficial dermis. In the vertical slice imaging mode the following characteristics were found: irregular entrance signal, destruction of layering, white streaks and dots, and grey areas. In contrast, the clinically healthy adjacent skin showed mainly a regular epidermal 'honeycomb' pattern in the en-face mode and distinct layering of the skin in the slice mode. CONCLUSIONS: HD-OCT with both the en-face and slice imaging modes offers additional information in the diagnosis of AK compared with conventional OCT and might enhance the possibility of the noninvasive diagnosis of AK prior to treatment procedures and possibly in the monitoring of noninvasive treatment strategies.

High-definition optical coherence tomography for the in vivo detection of demodex mites.

BACKGROUND: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. METHODS: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. RESULTS: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3-5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. CONCLUSION: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases.