Differential Diagnostics of Toxic Epidermal Necrolysis (Lyell’s Syndrome) in ICU: Case Reports

Toxic epidermal necrolysis (TEN) is a critical life-threating condition developing as the total detachment of epidermidis and characterized by severe pathological reactions of all body systems. The current article describes two cases of TEN with similar clinical and laboratory signs. In one case the diagnosis of TEN was subsequently refused.The objective: analysis of methods of clinical and differential diagnostics of conditions accompanied with massive epidermidis detachment in ICU patients.Results. The immunomorphological evaluation of skin specimen obtained from the patient with a torpid form of TEN showed linear IgG fixation in the intercellular space of stratum basale, stratum spinosum and stratum granulosum and C3 fixation in the intercellular space of stratum basale.Conclusion. The complex of anamnesis data and pathomorphological evaluation of skin are crucial for the diagnosis and treatment of patients with atypical TEN.

Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

Skin specimen as an alternative to brain tissue for post mortem rabies diagnosis in animals to scale up animal rabies surveillance

Background: Detection of the virus or some of its specific components using WHO and OIE recommended standard laboratory tests is the only way to get a reliable diagnosis of rabies. Brain tissue is the preferred specimen for post-mortem diagnosis of rabies in both humans and animals. Higher biosecurity requirements, skill and transportation facilities required for collection and transport of brain or whole carcass to the laboratory is one of the reasons for the poor rabies surveillance in animals. Point of care testing with simple, reliable and easy to operate devices would be an ideal approach for providing rapid results. Methods: The study evaluated diagnostic performance of two reference tests, DFAT and RTPCR on skin specimen, to assess its suitability as an alternative of brain tissue for post mortem rabies diagnosis in animals. Brain tissue and skin sample belonging to different species of animals (n=90) collected at necropsy were compared using Fluorescent Antibody Test and RT PCR, internationally approved methods for rabies diagnosis. Results: Validation of RT-PCR on skin and DFAT on skin in comparison with DFAT on brain as gold standard gave a sensitivity of 98% (95% CI:94.1-100) and 80% (95%CI:71.8-88.2) respectively. Specificity was 100% in both tests. Conclusion: The findings highlight the potential of skin specimen for improving rabies surveillance in animals especially in resource poor countries.

Skin RT-QuIC Assays are More Sensitive than CSF RT-QuIC in Prion Detection for Chinese Probable Sporadic Creutzfeldt-Jakob Disease

BackgroundThe definite diagnosis of human sporadic Creutzfeldt-Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of prion RT-QuIC of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. However the diagnostic potential of RT-QuIC of skin specimen for probable sCJD is not well researched. This study is to evaluate the diagnostic potential of RT-QuIC of skin specimen in human prion diseases.MethodsWe collected the paired skin and CSF samples from 29 recruited alive patients referred to Chinese CJD surveillance center, including 12 probable sCJD, 9 non-CJD, 3 genetic prion disease (gPrD) and 5 cases whose diagnoses still pending. The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate.ResultsAll 12 probable sCJD patients, 4 pending, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while all 9 non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 5 probable sCJD patients.ConclusionsOur preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

Bullous Scabies Simulating Pemphigoid

Background: Scabies is a contagious infestation affecting subjects of all ages, races, and social conditions. Objective: We report a case of a 79-year-old man who developed a bullous pemphigoid-like eruption. He presented to our unit 4 months after the onset of symptoms. An autoimmune bullous disease was suspected. Direct immunofluorescence on a skin specimen and anti-desmoglein 1, anti-desmoglein 3, and anti-bullous pemphigoid antigen 180 were negative. Surprisingly, the histology of a skin lesion demonstrated the presence of scabies, which was successfully treated with benzyl benzoate 20%. Conclusion: The diagnosis of bullous scabies should be considered for any bullous eruptions accompanied by papules and itching resistant to steroid treatment and with negative immunopathologic findings.

Autologous cultured single-keratinocytes in fibrin glue suspension in chronic venous leg ulcers

SummaryThe aim of this work was to apply the cultured autologous keratinocytes in fibrin glue suspension in treatment of chronic non-healing venous leg ulcers. 32 patients with chronic leg ulcers caused by venous insufficiency were treated. The surface of ulcers covered 14.2 cm2 to 48.6 cm2. The duration of leg ulcer was between 4 to 20 years. The skin specimen 1.0 × 1.0 cm was taken from the buttock of each patient, from which keratinocytes were obtained. Next those cells were cultured. After 7 days the keratinocytes in fibrin glue were applied to the wound bed. After 2 weeks of treatment the ulceration of 13 patients healed completely whereas the ulcer formation of the rest of the patients diminished by 30%. In all patients the process of healing was successfully completed after further 4 weeks. Our method shows that a rapid healing chronic venous leg ulcer can be achieved by keratinocytes in fibrin glue suspension.