Treatment of a Severe Pediatric Lyell Syndrome with Amniotic Membrane: Case Report and Histological Findings

Background: Lyell Syndrome (TEN, Toxic epidermal necrolysis) represents a medical emergency particularly in pediatric patients in whom the massive skin damage can quickly lead to multi-organ dysfunction and death. Prompt restoration of the physiologic mucosal/cutaneous barrier is mandatory. The use of amniotic membranes has been described in the treatment of ophthalmic Lyell Syndrome, but its use has not yet been adopted for the management of larger cutaneous wounds. Study Hypothesis: Here we report the use of amniotic membranes in a pediatric case of severe Lyell Syndrome with complete skin surface, ocular and mucosal involvement with life threating presentation. Methods: A 7-year old female was admitted to our Burn Centre for severe cutaneous/mucosal exfoliation (100% Total body surface area, TBSA) as a result of an adverse reaction to ibuprofen administration. Supportive fluid administration, cardiac-pulmonary assistance and pain management were complemented by serial grafting of amniotic membranes on all affected areas to provide coverage of the exfoliated skin/mucosa. Biopsies were obtained to monitor histological skin changes. Results: The patient showed an excellent response to amniotic membrane treatment, with rapid restoration of mucosal and cutaneous layers in the grafted areas. This resulted in a decreased need for dressing changes, avoidance of additional surgeries and a reduced dependence on supportive therapy. Lower pain levels than usually expected led to a reduced need for narcotic pain medications and allowed for early physical rehabilitation and a short hospital stay. Histology confirmed evidence of topical immune-modulation in treated areas (reduction of inflammatory infiltrate). Conclusion: As we tested in numerously TEN and burn pediatric injuries Amniotic membranes with their regenerative and immune-modulatory effects may represent an life saving treatment even in the worst cases of pediatric Lyell syndrome.

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A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Genes ◽

10.3390/genes12050716 ◽

2021 ◽

Vol 12 (5) ◽

pp. 716

Author(s):

Daniele Castiglia ◽

Paola Fortugno ◽

Angelo Giuseppe Condorelli ◽

Sabina Barresi ◽

Naomi De Luca ◽

...

Keyword(s):

Amniotic Membrane ◽

Epidermolysis Bullosa ◽

Ocular Involvement ◽

Human Amniotic Membrane ◽

Vitro Assay ◽

Junctional Epidermolysis Bullosa ◽

Mucosal Involvement ◽

Skin Fragility ◽

Laminin 332

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

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Immunosuppression and Immunotherapy

10.1093/med/9780190684747.003.0010 ◽

2018 ◽

Author(s):

Eelco F. M. Wijdicks ◽

Sarah L. Clark

Keyword(s):

Intensive Care Unit ◽

Plasma Exchange ◽

Immune Modulation ◽

Supportive Therapy ◽

Autoimmune Encephalitis ◽

Cord Compression ◽

High Dose ◽

Neurologic Complications ◽

Controlled Clinical Trials ◽

Precautionary Measures

Immune modulation in the neurosciences intensive care unit mostly involves high-dose corticosteroids, plasma exchange, and immunoglobulin. Corticosteroids are frequently used in patients with neurologic complications of cancer. Neurosurgeons typically use corticosteroids after performing a craniectomy to reduce cerebral edema. Corticosteroids are the established initial treatment modality of choice for patients with acute metastatic epidural spinal cord compression. Therapeutic apheresis or immunoglobulin is generally used as supportive therapy in patients with Guillain-Barré syndrome, myasthenia crisis, and autoimmune encephalitis. Immune modulation has been considered essential in autoimmune encephalitis despite lack of controlled clinical trials. In these now better characterized disorders, a combination of corticosteroids, intravenous immune globulin (IVIG), plasma exchange, rituximab, or cyclophosphamide are used. The use of acute immunotherapy and precautionary measures are discussed in this chapter.

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Is Immune Modulation the Mechanism Underlying the Beneficial Effects of Amniotic Cells and Their Derivatives in Regenerative Medicine?

Cell Transplantation ◽

10.3727/096368916x693699 ◽

2017 ◽

Vol 26 (4) ◽

pp. 531-539 ◽

Cited By ~ 27

Author(s):

Antonietta R. Silini ◽

Marta Magatti ◽

Anna Cargnoni ◽

Ornella Parolini

Keyword(s):

Immune Response ◽

Regenerative Medicine ◽

Amniotic Membrane ◽

Stromal Cells ◽

Immune Modulation ◽

Cell Replacement ◽

Beneficial Effects ◽

Repair Mechanisms ◽

Altered Immune Response ◽

Amniotic Cells

Regenerative medicine aims to repair and regenerate damaged cells, tissues, and organs in order to restore function. Regeneration can be obtained either by cell replacement or by stimulating the body's own repair mechanisms. Importantly, a favorable environment is required before any regenerative signal can stimulate resident stem/stromal cells, and regeneration is possible only after the resolution of injury-induced inflammation. An exacerbated immune response is often present in cases of degenerative, inflammatory-based diseases. Here we discuss how amniotic membrane cells, and their derivatives, can contribute to the resolution of many diseases with altered immune response by acting on different inflammatory mediators.

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Sutureless Amniotic Membranes (ProKera) for Filamentary Keratitis: A Case Series

Journal of Dry Eye Disease ◽

10.22374/jded.v2i1.10 ◽

2019 ◽

Vol 2 (1) ◽

pp. e10-e16

Author(s):

Jennifer S Harthan ◽

Lindsay A Sicks

Keyword(s):

Amniotic Membrane ◽

Ocular Surface ◽

Management Strategies ◽

Anterior Segment ◽

Case Series ◽

Signs And Symptoms ◽

Traditional Therapies ◽

Amniotic Membranes ◽

Ocular Signs

Purpose To report a case series of refractory filamentary keratitis successfully managed with sutureless amniotic membranes resistant to other management strategies. Methods Three cases are discussed with anterior segment photography who were diagnosed with filamentary keratitis and successfully managed with sutureless amniotic membranes, after experiencing limited relief with standard treatments. Conclusions This case series demonstrates the complex management of patients with filamentary keratitis who had failed with traditional therapies and were successfully managed with sutureless amniotic membranes. All three patients demonstrated improvement in both ocular signs and symptoms following amniotic membrane application to the ocular surface.

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Fracture toughness of human amniotic membranes

Interface Focus ◽

10.1098/rsfs.2019.0012 ◽

2019 ◽

Vol 9 (5) ◽

pp. 20190012 ◽

Cited By ~ 1

Author(s):

Ching Theng Koh ◽

Khaow Tonsomboon ◽

Michelle L. Oyen

Keyword(s):

Mechanical Property ◽

Fracture Toughness ◽

Amniotic Membrane ◽

Nonlinear Material ◽

Fetal Membrane ◽

Uniaxial Tensile ◽

Shear Mode ◽

Uniaxial Tensile Test ◽

Membrane Rupture ◽

Amniotic Membranes

Amnion is a membrane that surrounds and structurally protects the developing fetus during pregnancy. The rupture of amniotic membranes prior to both normal and preterm deliveries involves stretch forces acting on a biochemically triggered weak zone of the membranes. Fracture toughness is an important mechanical property describing how the membranes containing a defect resist fracture, but this property has never been investigated in amniotic membranes. In this work, the fracture toughness of many samples cut from four pieces of amniotic membrane from different mothers was examined by uniaxial and pure shear (mode I) fracture tests. The measurement was checked for dependence on the sample geometry and notch length. Results from the uniaxial tensile test show J-shaped stress–strain curves and confirm that the amniotic membrane is a nonlinear material. The measured fracture toughness of four amniotic membranes ranged from 0.96 ± 0.11 to 1.83 ± 0.18 kJ m −2 . Despite considering the effect of the presence of the defect on mechanical property measurement, similar fracture behaviour was observed for pre-notched and unnotched specimens, indicating that the membranes were extremely tolerant to defects. This defect-tolerant characteristic provides insight into the understanding of fetal membrane rupture.

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Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome

Case Reports in Ophthalmological Medicine ◽

10.1155/2020/6760272 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Han Y. Yin ◽

Nicholas Hadjokas ◽

Kanish Mirchia ◽

Robert Swan ◽

Samuel Alpert

Keyword(s):

Total Body Surface Area ◽

Supportive Therapy ◽

Maculopapular Rash ◽

Acute Onset ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Johnson Syndrome ◽

Eye Involvement ◽

Total Body

Purpose. To report an unusual presentation of commercial cannabidiol (CBD) oil-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS-TEN). Methods. A 56-year-old woman presented with acute onset of a diffuse, blistering, maculopapular rash with over 30% total body surface area (BSA) involvement two days after taking CBD oil sublingually for chronic pain. Biopsy confirmed SJS-TEN. Ophthalmology was consulted and mild eye involvement was found. She was started on topical cyclosporine, prednisone, moxifloxacin, and erythromycin ointment to prevent progression, which was successful. She was otherwise treated with supportive therapy in the intensive care burn unit and ultimately passed away from septic shock. Conclusion. In this case, we described an unusual drug-induced SJS from a commercial, non-FDA-regulated cannabis product. The use of a commercial CBD product should be cautioned due to potential for series of drug reactions to the cannabis product and the risk for reaction to other unregulated other pharmacological components.

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Amniotic membrane graft in a recurrent re-fusing temporal tarsorrhaphy: a case report

Therapeutic Advances in Ophthalmology ◽

10.1177/2515841420971927 ◽

2020 ◽

Vol 12 ◽

pp. 251584142097192

Author(s):

G. Bryant Giles ◽

Donovan S. Reed ◽

Timothy A. Soeken ◽

Brett W. Davies

Keyword(s):

Skin Graft ◽

Amniotic Membrane ◽

Motor Vehicle ◽

Motor Vehicle Accident ◽

Total Body Surface Area ◽

Skin Grafting ◽

Vehicle Accident ◽

Graft Donor ◽

Total Body ◽

Amniotic Graft

Amniotic membrane grafts (AMGs) are commonly used to treat a variety of ophthalmologic conditions. Complications exist with permanent tarsorrhaphies, including the risk of re-fusion following tarsorrhaphy separation. We report a novel application of amniotic graft in lieu of skin grafts to protect the exposed marginal surface during the initial re-epithelialization period following release of a permanent tarsorrhaphy. We present a 24-year-old man who sustained an 80% total body surface area burn from a motor vehicle accident 16 months prior to presentation at our Oculoplastic service for evaluation of residual lagophthalmos. His original permanent tarsorrhaphies were removed; however, re-fusion occurred temporally in both sides. During a second attempt, AMGs were secured over the eyelid margins, leading to a successful tarsorrhaphy takedown without re-fusion. Periocular burn injuries present particular challenges, as cicatricial changes continue to evolve and viable skin graft areas diminish with each successive graft. In the setting of recurrent auto-tarsorrhaphy, the AMG has shown to be a viable alternative to standard skin grafting. This case demonstrates excellent results in a skin graft sparing procedure that is effective and efficient. Amniotic membrane grafting reduces morbidity by foregoing skin graft donor sites and can achieve similar functional and cosmetic results to standard skin grafting with reduced overall surgical time. As such, AMGs have the potential to supplant standard skin grafting in cases of recurrent auto-tarsorrhaphy, particularly in the setting of diminished available healthy skin tissue.

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Allopurinol: Attention to the Prescription!

Journal of Clinical Cases & Reports ◽

10.46619/joccr.2020.2.s2-1002 ◽

2020 ◽

Vol 3 (S2) ◽

pp. 3-6

Author(s):

Achehboune Kaoutar ◽

◽

Baybay Hanane ◽

Douhi Zakia ◽

Elloudi Sara ◽

...

Keyword(s):

Clinical Symptoms ◽

Balance Sheet ◽

Clinical Manifestations ◽

Topical Steroid ◽

Stevens Johnson Syndrome ◽

Dermatology Department ◽

Johnson Syndrome ◽

Mucosal Involvement ◽

Lyell Syndrome ◽

Systemic Symptoms

Allopurinol is a commun hypo-uricemic drug. However, it is main drug reported to be inducing toxidermy. Our goal is to encourage limiting the prescription of this drug and to reserve it for justified cases after some observations. A Retrospective study was conducted in the Dermatology department between 2012 and 2019. We collected all toxidermy cases following Allopurinol. During the study period,39 cases of severe Allopurinol toxidermia, including 22 women and 17 men, a sex ratio of 0.77. The average age was 65 years old. Most of the patients were "poly-medicated". The average time between medication and clinical symptoms was 28.25 days. Clinical manifestations were: macula-papular rash in 12 cases (30%), erythroderma in 14 cases (35%), purpura in 7 cases (17%) and mucosal involvement in 20 cases. Fever in 29 cases, a state of shock in 5 cases. 10 patients required a transfer in intensive care. On the balance sheet; eosinophilia was found in 23 cases, 18 cases of hepatic cytolysis, CPK mb was elevated in 17 cases, acute renal failure in 24 cases. The biopsy was performed in all cases confirming the toxidermy. The Drug reaction eosinophilia and systemic symptoms (DRESS) retained in 29 cases, Stevens-Johnson syndrome (SJS) in 2 cases, Lyell in 4 cases. The management involved stopping the incriminated drug (Allopurinol) and the introduction of an antihistamine and an emollient were prescribed in all patients. Topical steroid in 21 patients. Oral corticosteroid therapy in 14 patients. A bolus of corticosteroid was administered in 4 patients. The evolution was good for 30 patients (77%). However, we recorded 9 deaths in a context of septic shock and multi-visceral failure. In our series, Allopurinol was the cause of severe toxidermia including Lyell syndrome, StevensJohnson and DRESS syndrome. The severity of these diseases should encourage preserving it for the justified cases, and knowing how to adapt the dosage to the renal function, to introduce the treatment in a progressive way and to stop the treatment in case of less signs of toxidermy. The control of the use of this molecule would reduce the cases of this disease.

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Characterization of Cryopreserved Canine Amniotic Membrane

Membranes ◽

10.3390/membranes11110824 ◽

2021 ◽

Vol 11 (11) ◽

pp. 824

Author(s):

Nathawan Withavatpongtorn ◽

Nalinee Tuntivanich

Keyword(s):

Tensile Strength ◽

Cell Viability ◽

Amniotic Membrane ◽

Cell Biology ◽

Light Transmission ◽

Testing Machine ◽

Blue Staining ◽

Corneal Transplant ◽

Stress Strain ◽

Amniotic Membranes

Amniotic membrane is an effective corneal reconstruction material in veterinary surgery. Cryopreserved amniotic membrane is widely used in practice. Properties of cryopreserved canine amniotic membranes are currently not well studied. This study aimed to compare three properties between canine amniotic membranes cryopreserved for 7 days and 30 days, including tensile strength, transparency, and cell viability. After their respective cryopreservation time, stress–strain curves of the cryopreserved membranes’ tensile strength were assessed using a universal testing machine. Both groups produced J-shaped stress–strain curves with statistically comparable parameters, including maximum stress, strain, and Young’s modulus. The percentage of cell viability was observed by trypan blue staining under a light microscope. Membrane transparency was tested with a spectrophotometer. Transparency tests showed high levels of light transmission and low haze, with no statistical difference between groups. Cell viability was statistically lower in the 30-day cryopreserved group. Tensile strength and transparency of cryopreserved CAM were not significantly impeded for up to 30 days. For CAM to be used as an alternative corneal transplant material in veterinary and regenerative medicine, further research on cell biology, biomechanical properties of the membrane, and cell viability should be conducted.

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MANAGEMENT OF ORAL LESIONS ASSOCIATED WITH CARBAMAZEPINE RELATED STEVENS-JOHNSON SYNDROME / TOXIC EPIDERMAL NECROLYSIS OVERLAP PATIENT

Dentika Dental Journal ◽

10.32734/dentika.v19i2.456 ◽

2016 ◽

Vol 19 (2) ◽

pp. 154-159

Author(s):

Dewi Puspasari ◽

Irna Sufiawati

Keyword(s):

Toxic Epidermal Necrolysis ◽

Fas Ligand ◽

Total Body Surface Area ◽

Stevens Johnson Syndrome ◽

Cytotoxic T Cell ◽

Mean Corpuscular Hemoglobin ◽

Oral Lesions ◽

Treatment Standard ◽

Johnson Syndrome ◽

Mucosal Involvement

Stevens–Johnson syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) are acute, self-limited, potentially life-threatening mucocutaneous disease. Oral mucosal involvement manifest as extensive erosions and haemorrhagic crusting, which can interfere oral functions causing odynophagia, inability to tolerate solid foods, and increased aspiration risk. A 40-year-old female patient was referred from Dermatology and Venereology department with diagnosis SJS/TEN overlap. The patient complained mouth opening difficulty due to mouth and lip sores. Drug history revealed positive intake of carbamazepine. Extraoral examination revealed multiple diffuse discrete facial lesions, conjunctival hyperemia, erosions and hemorrhagic crusting lips. Intraoral examination revealed white yellowish plaque, and erosions on buccal mucosa, palate, floor of the mouth, dorsal, ventral, and lateral tongue. Laboratory investigation revealed decrease of haemoglobin, hematocrite, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), thrombocyte, eosinophil, band of eosinophil, lymphocyte, natrium, potassium, and calcium. Oral lesions associated with SJS/TEN overlap diagnosis was made. Chlorhexidine gluconate 0,1%, nystatin oral suspension, vitamin B12, folic acid, and corticosteroid unguent compounding were given, which showed improvement of oral lesions in 3 weeks. SJS/TEN are the same disease spectrum of delayed hypersensitivity reaction leading to keratinocyte apoptosis through cytotoxic T-cell mediated Fas-Fas ligand, perforin/ granzyme B, and granulysin, which distinguished primarily by severity and percentage of total body surface area involved.Currently, an optimal treatment standard for SJS/TEN patients remains unavailable. Oral lesions management play significant role in enhancing patients’ quality of life and achieving better prognosis in SJS/TEN overlap patients through multidisciplinary approach.

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