60: Inherited Epidermolysis Bullosa

Question 1

What are the key characteristics of Dystrophic Epidermolysis Bullosa (DEB)?

Answer 1

Dystrophic Epidermolysis Bullosa is characterized by:
- Blisters that heal with scarring and milium formation.
- Defects in the anchoring fibrils, leading to sublamina densa separation.
- Extensive involvement of the oropharynx in both dominant and recessive forms, causing generalized erosions that limit tongue movement and narrow the oral cavity.

Question 2

What molecular pathology is associated with Dystrophic Epidermolysis Bullosa?

Answer 2

• Abnormalities of anchoring fibrils range from subtle changes in dominant disease to absence in severe recessive forms.
• Indirect immunofluorescent microscopy shows varying degrees of linear collagen VII staining at the DEJ in dominant patients and absent staining in severe recessive patients.
• Mutations in the gene coding for Collagen VII (COL7A1) are common, with recessive forms usually causing premature termination codons leading to lack of collagen VII in tissue.

Question 3

What are the clinical features of Autosomal Recessive Dystrophic Epidermolysis Bullosa (RDEB)?

Answer 3

• Increased prevalence of invasive squamous cell carcinoma.
• RDEB mitis: localized form, usually confined to repetitively traumatized skin surfaces, often in an acral distribution; scarring and milium formation accompany healing.
• Hallopeau-Siemens: presents with generalized blistering at birth, may involve extensive denudation of skin, and can lead to progressive scarring and pseudosyndactyly.

Question 4

What are the implications of mutations in Collagen VII (COL7A1) for Dystrophic Epidermolysis Bullosa?

Answer 4

• Mutations can lead to premature termination codons, resulting in lack of collagen VII in tissue.
• Some mutations do not cause premature termination and produce less severe disease.
• Glycine substitution in the triple helical region can interfere with the assembly of collagen VII, leading to conditions like EB pruriginosa.

Question 5

What are the common features of Hallopeau-Siemens type of RDEB?

Answer 5

• Presents with generalized blistering at birth.
• May involve extensive denudation of an entire region of skin, often affecting one limb.
• Associated with Bart syndrome and congenital absence of skin.
• Healing and blistering cycles during infancy can lead to progressive scarring and flexion contracture of hands and limbs.

Question 6

What is the likely diagnosis for a newborn with generalized blistering and extensive denudation of skin involving one limb?

Answer 6

The likely diagnosis is Hallopeau-Siemens Recessive Dystrophic Epidermolysis Bullosa (RDEB). It is associated with mutations in the COL7A1 gene, which encodes Collagen VII.

Question 7

What genetic mutation is most likely responsible for extensive blistering and scarring in severe RDEB?

Answer 7

The most likely mutation is in the COL7A1 gene, which encodes Collagen VII.

Question 8

What is the underlying cause of mitten pseudosyndactyly in severe RDEB?

Answer 8

Mitten pseudosyndactyly is caused by progressive scarring that leads to the closure of digits in a ‘mitten’ of skin.

Question 9

How do mutations in the gene coding for Collagen VII (COL7A1) affect the severity of Dystrophic Epidermolysis Bullosa?

Answer 9

Mutations in the COL7A1 gene can lead to varying severities of Dystrophic Epidermolysis Bullosa:
- In recessive forms, mutations often cause premature termination codons, resulting in a lack of collagen VII in tissue.
- Truncated proteins may not assemble into anchoring fibrils, explaining the absence of detectable collagen VII in severe cases.
- Mutations that do not cause premature termination codons typically result in less severe disease.

Question 10

What are the clinical implications of RDEB mitis and Hallopeau-Siemens forms of Autosomal Recessive Dystrophic Epidermolysis Bullosa (RDEB)?

Answer 10

The clinical implications of RDEB mitis and Hallopeau-Siemens forms include:

Form | Characteristics |
|———————|—————————————————————————————————-|
| RDEB mitis | - Localized form, usually confined to traumatized skin surfaces, often in an acral distribution.
| | - Accompanied by scarring and milium formation during healing.
| | - Mucosal involvement is mild if present. |
| Hallopeau-Siemens | - Presents with generalized blistering at birth.
| | - May have extensive denudation of skin, often involving limbs.
| | - Associated with Bart syndrome and congenital absence of skin.
| | - Healing cycles can lead to progressive scarring and pseudosyndactyly.

Question 11

What are the key differences in periorificial involvement between severe JEB and RDEB?

Answer 11

Patients with RDEB do not show significant periorificial involvement, unlike those with severe JEB.

Question 12

What complications can arise from mucosal erosions in RDEB patients?

Answer 12

Mucosal erosions of the esophagus can lead to stricture formation and webbing, complicating swallowing and nutrition.

Question 13

What are the common dental issues associated with RDEB?

Answer 13

Patients often experience significant enamel pitting and extensive caries, which can contribute to malnutrition and growth retardation.

Question 14

What is the prognosis for patients with localized Autosomal Dominant Dystrophic Epidermolysis Bullosa (DDEB)?

Answer 14

Patients with localized DDEB generally have a good prognosis and can expect a normal lifespan.

Question 15

How does generalized Autosomal Dominant Dystrophic Epidermolysis Bullosa (DDEB) differ from localized DDEB?

Answer 15

Generalized DDEB presents at birth with a more severe and widespread blistering phenotype compared to localized DDEB, which is less severe and may not be apparent until childhood.

Question 16

What are the common features of nail abnormalities in DDEB patients?

Answer 16

Nail dystrophy and nail loss with atrophic scarring of the distal digits are common in DDEB patients, and sometimes nail abnormalities can be the only presenting symptom.

Question 17

What is the prognosis for a patient with localized DDEB presenting with dystrophic nails and milia?

Answer 17

The prognosis for localized DDEB is good, with a normal lifespan.

Question 18

What factors contribute to malnutrition in a patient with severe RDEB?

Answer 18

Factors include oral lesions, dental caries, esophageal strictures, and increased caloric needs. Management includes nutritional support and gastrostomy tube insertion if necessary.

Question 19

What distinguishes SCC in RDEB from other cutaneous SCCs?

Answer 19

SCC in RDEB is extremely aggressive with a strong tendency for invasion and metastasis.

Question 20

What other features are commonly associated with localized DDEB besides dystrophic nails?

Answer 20

Other features include blistering localized to traumatized areas, milia, and atrophic scarring of the distal digits.

Question 21

What are the key differences in clinical presentation between severe Junctional Epidermolysis Bullosa (JEB) and Recessive Dystrophic Epidermolysis Bullosa (RDEB)?

Answer 21

• RDEB patients do not show significant periorificial involvement unlike severe JEB.
• The scalp is the most affected area in RDEB.
• RDEB patients often experience anemia and may have iron absorption deficiencies.
• RDEB is associated with oral lesions, dental caries, and esophageal strictures leading to increased caloric needs and potential malnutrition.
• SCC (squamous cell carcinoma) is common in RDEB, with 50-80% developing these carcinomas, which are aggressive and have strong tendencies for invasion and metastasis.

Question 22

What are the distinguishing features of localized versus generalized Autosomal Dominant Dystrophic Epidermolysis Bullosa (DDEB)?

Answer 22

Feature | Localized DDEB | Generalized DDEB |
|———|—————-|——————|
| Onset | Can present at birth, but may not be appreciated until childhood | Presents at birth with a more severe phenotype |
| Blistering | Localized to traumatized areas (knees, sacrum, acral surfaces) | More widespread blistering |
| Nail Abnormalities | Nail dystrophy and loss are common | Often show dystrophic or absent nails |
| Oral Lesions | Not common, teeth usually unaffected | Oral erosions can be present but not extensive |
| Prognosis | Good prognosis, normal lifespan | Varies, may have more complications |

Question 23

What are the key characteristics of Kindler syndrome?

Answer 23

• EB-like trauma-induced blistering at birth and during infancy, with atrophic changes during healing.
• In late childhood, blistering subsides and leads to progressive poikiloderma in sun-exposed areas.
• Poikiloderma may show areas of atrophy, hyperkeratosis, hypopigmentation, hyperpigmentation, and telangiectasia.
• Often presents with photosensitivity.
• Possible nail changes and webbing of toes and fingers, along with internal complications like oral inflammation and strictures.
• Ultrastructurally, there is reduplication of the basement membrane, which is the most consistent feature.

Question 24

What is the first step in the diagnosis of Kindler syndrome?

Answer 24

The first step in diagnosis involves:
1. Thorough history and physical examination (PE):
- Age of onset of blistering
- Presence of blistering in other family members
- Review of systems (ROS) including GI, Respiratory, Ocular, Dental, and Genitourinary symptoms
- Complete skin exam and evaluation of mucosal tissues, hair, nails, and teeth
- Laboratory examination for anemia and serum albumin.

Question 25

What is the significance of skin biopsy in the diagnosis of Kindler syndrome?

Answer 25

- It is critical to **biopsy a blister as fresh as possible** because the interior of blisters rapidly reepithelializes, which can obscure correct determination of blister levels. - A biopsy should cover **10% visible blister and 90% intact skin**. - **Transmission electron microscopy** is considered the **gold standard** for diagnosis. - Pathognomonic findings include clumping of keratin intermediate filaments in basal keratinocyte cytoplasm for severe generalized EBS.

Question 26

What are the steps involved in gene mutation analysis for Kindler syndrome?

Answer 26

The steps involved in gene mutation analysis include: 1. **Blood samples or buccal swabs** are taken from the patient. 2. Samples are also collected from **parents and siblings** for genetic analysis to identify mutations associated with Kindler syndrome.

Question 27

What are the characteristic features of poikiloderma in Kindler syndrome?

Answer 27

Poikiloderma in Kindler syndrome includes areas of atrophy, hyperkeratosis, hypopigmentation, hyperpigmentation, and telangiectasia, often in sun-exposed areas.

Question 28

What is the most consistent ultrastructural feature of Kindler syndrome?

Answer 28

The most consistent ultrastructural feature is reduplication of the basement membrane.

Question 29

What internal complications are commonly associated with Kindler syndrome?

Answer 29

Internal complications include oral inflammation, esophageal or ureteral strictures, and ectropion.

Question 30

What diagnostic steps should be taken to confirm Kindler syndrome?

Answer 30

Diagnostic steps include a thorough history and physical exam, skin biopsy, and genetic analysis for KIND1 mutations.

Question 31

What ultrastructural abnormalities are associated with photosensitivity in Kindler syndrome?

Answer 31

Ultrastructural abnormalities include reduplication of the basement membrane and sublamina densa splits.

Question 32

What are the key clinical features of Kindler syndrome that differentiate it from other forms of epidermolysis bullosa?

Answer 32

Key clinical features of **Kindler syndrome** include: - **EB-like trauma-induced blistering** at birth and during infancy. - **Progressive poikiloderma** in late childhood, affecting sun-exposed areas. - Areas of **atrophy, hyperkeratosis, hypopigmentation, hyperpigmentation, and telangiectasia**. - **Photosensitivity** is often present. - **Nail changes** and webbing of toes and fingers, with potential internal complications such as oral inflammation and strictures. - Ultrastructural findings include **reduplication of the basement membrane**, which is the most consistent feature.

Question 33

What is the significance of performing a skin biopsy in the diagnosis of epidermolysis bullosa, particularly in Kindler syndrome?

Answer 33

The significance of performing a **skin biopsy** in the diagnosis of epidermolysis bullosa, especially in **Kindler syndrome**, includes: 1. **Timeliness**: It is critical to biopsy a blister as fresh as possible to avoid rapid reepithelialization, which can obscure the determination of blister levels. 2. **Diagnostic Accuracy**: A biopsy can reveal: - **10% coverage of visible blister** and **90% intact skin**. - **Transmission electron microscopy** is considered the **gold standard** for identifying structural abnormalities. - Pathognomonic findings such as **clumping of keratin intermediate filaments** in basal keratinocyte cytoplasm for severe generalized forms. 3. **Localization of Antigens**: Indirect immunofluorescent microscopy can help localize antigens to determine the level of skin separation in the basement membrane zone (BMZ).

Question 34

What steps should be taken in the genetic analysis for diagnosing Kindler syndrome, and why is it important?

Answer 34

The steps for **genetic analysis** in diagnosing **Kindler syndrome** include: 1. **Sample Collection**: Blood samples or buccal swabs are taken from the patient, as well as from parents and siblings. 2. **Genetic Testing**: The samples are analyzed for mutations in genes associated with epidermolysis bullosa, particularly those related to **kindlin 1**. **Importance**: - **Confirmatory Diagnosis**: Genetic analysis helps confirm the diagnosis of Kindler syndrome by identifying specific mutations. - **Family Planning**: Understanding the genetic basis can aid in genetic counseling for affected families. - **Tailored Management**: Knowledge of the specific genetic mutation can guide treatment strategies and management of complications.

Question 35

What are the key components of genetic counseling for Epidermolysis Bullosa (EB)?

Answer 35

- Analysis of chorionic villus sampling as early as **8 to 10 weeks**.

Question 36

What is epidermolysis bullosa related to?

Answer 36

Epidermolysis bullosa is particularly related to kindlin 1.

Question 37

What is the importance of genetic analysis in Kindler syndrome?

Answer 37

Genetic analysis helps confirm the diagnosis of Kindler syndrome by identifying specific mutations.

Question 38

How does genetic counseling assist affected families of Epidermolysis Bullosa (EB)?

Answer 38

Understanding the genetic basis can aid in genetic counseling for affected families.

Question 39

What is the primary goal of treatment for Epidermolysis Bullosa (EB)?

Answer 39

The primary goal of treatment for EB is avoidance of trauma.

Question 40

What are the recommended strategies for supportive skin care in EB?

Answer 40

1. Prevention of infection: - Modified Dakin solution (0.025% w/v sodium hypochlorite) for 20 mins - Mupirocin or other topical antibiotics - Semiocclusive nonadhesive dressings (avoid using tape) - Self-adhering gauze or self-adherent paper to hold nonadherent dressings in place 2. For EBS: - Control exposure to heat - Use soft, well-ventilated shoes 3. For DEB: - Finger splinting or diligent hand wrapping - Hand protection

Question 41

What are common infection agents in Epidermolysis Bullosa (EB) and their management?

Answer 41

Common infection agents include Staphylococcus aureus and Streptococcus pyogenes. Management includes skin cultures and appropriate systemic antibiotics for wound infection, gentle whirlpool therapy, frequent daily dressing changes, dilute chlorine baths, rotation of topical antibiotics, and use of topical disinfectants (povidone iodine) to reduce resistant bacteria.

Question 42

What surgical treatments are recommended for severe RDEB?

Answer 42

Surgical treatment for severe RDEB (Hallopeau Siemens) includes addressing mitten psudosyndactyly, splinting after surgery to reduce recurrence of hand deformities, correction of limb, perioral, and perineal contracture deformities, though recurrence is common, and minimizing trauma to oral mucosa during intubation.

Question 43

What is the significance of tumors in RDEB and their management?

Answer 43

SCC (squamous cell carcinoma) often arises after puberty in RDEB and may occur in multiple primary sites, especially in nonhealing areas. Management includes surgical excision using either Moh’s or non-Moh’s approaches as an important first-line modality, radiation therapy as a useful adjunct, and isotretinoin has been used for chemoprevention.

Question 44

What chemopreventive agent has been used for aggressive SCC in RDEB?

Answer 44

Isotretinoin has been used for chemoprevention in SCC associated with RDEB.

Question 45

What genetic counseling options are available for at-risk families of severe RDEB?

Answer 45

Options include genetic screening of at-risk pregnancies using chorionic villus sampling or amniocentesis.

Question 46

What systemic antibiotics are indicated for wound infections in severe RDEB?

Answer 46

Systemic antibiotics should be chosen based on skin culture results to target specific pathogens like Staphylococcus aureus or Streptococcus pyogenes.

Question 47

What surgical intervention is recommended for mitten pseudosyndactyly in severe RDEB?

Answer 47

Surgical intervention for mitten pseudosyndactyly involves releasing the digits. Postoperative splinting is essential, but recurrence of hand deformities is common.

Question 48

What diagnostic options are available during pregnancy for a woman with a family history of EB?

Answer 48

Diagnostic options include chorionic villus sampling as early as 8-10 weeks of gestation and amniocentesis in the second trimester.

Question 49

What preventive measures can be taken for patients with EBS experiencing frequent blistering in hot weather?

Answer 49

Preventive measures include controlling exposure to heat, using soft, well-ventilated shoes, and avoiding trauma to the skin.

Question 50

What treatment options are available for aggressive squamous cell carcinoma (SCC) in RDEB?

Answer 50

Treatment options include surgical excision (Moh’s or non-Moh’s approaches) and radiation therapy as an adjunct. SCC in RDEB is highly aggressive with a strong tendency for invasion and metastasis.

Question 51

What strategies can be employed to prevent and manage recurrent infections in severe RDEB?

Answer 51

Strategies include using modified Dakin solution, mupirocin or other topical antibiotics, semiocclusive nonadhesive dressings, and systemic antibiotics for wound infections.

Question 52

What surgical and postoperative measures are recommended for extensive scarring and flexion contractures in severe RDEB?

Answer 52

Surgical release of contractures is recommended, followed by splinting to reduce recurrence.

Question 53

What topical therapies can be used to prevent infection in severe RDEB?

Answer 53

Topical therapies include modified Dakin solution, mupirocin, and semiocclusive nonadhesive dressings.

Question 54

What are the key components of genetic counseling for Epidermolysis Bullosa (EB) during pregnancy?

Answer 54

Key components include chorionic villus sampling as early as 8 to 10 weeks of gestation, amniocentesis in the second trimester, and development of highly informative intragenic and flanking polymorphic DNA markers for candidate genes, allowing for rapid screening of genetic hotspots to assess risk in pregnancies.

Question 55

What are the common gastrointestinal complications associated with RDEB and JEB?

Answer 55

Common gastrointestinal complications include esophageal lesions, esophageal strictures, and the need for gastrostomy tube insertion. Management includes increased fluid and fiber intake, and stool softeners may help with constipation and colitis.

Question 56

What are the ocular complications seen in patients with RDEB and JEB?

Answer 56

Ocular complications include Dowling Meara, corneal ulcerations, and cicatricial conjunctivitis in RDEB. Treatment includes antibiotic ointments and cycloplegic agents to reduce ciliary spasms.

Question 57

What nutritional challenges do patients with EB face?

Answer 57

Nutritional challenges include oropharyngeal and GI lesions posing the greatest threat to nutritional well-being, anemia of chronic disease, and severe iron deficiency in RDEB patients.

Question 58

What psychological aspects are associated with Epidermolysis Bullosa?

Answer 58

Patients are often plagued with chronic pain and it is important to identify warning signs of depression in these patients.

Question 59

What are the recommendations for oral hygiene in EB patients?

Answer 59

Good dental hygiene is essential for EB patients. Mouthwashes containing alcohol or harsh agents should be avoided. Normal saline rinses are effective for gentle cleaning of the mucosal surfaces.

Question 60

What is the recommended management strategy for esophageal strictures in RDEB?

Answer 60

Esophageal strictures in RDEB are managed with dilation, though recurrence is common. Gastrostomy tube insertion may be necessary for nutrition.

Question 61

What treatments are recommended for corneal ulcerations and scarring in patients with JEB?

Answer 61

Treatments include antibiotic ointments, cycloplegic agents to reduce ciliary spasms, moisture chambers, ocular lubricants, and surgical interventions like full-thickness skin grafting for severely affected eyelids.

Question 62

What additional treatments should be considered for severe RDEB patients with chronic anemia unresponsive to oral iron?

Answer 62

Assess erythropoietin (EPO) levels and treat with recombinant EPO if necessary. Blood transfusions may also be required.

Question 63

What measures can improve oral function and hygiene in severe RDEB patients with microstomia and ankyloglossia?

Answer 63

Measures include avoiding mouthwashes with alcohol, using normal saline rinses for gentle cleaning, and maintaining good dental hygiene.

Question 64

What is the role of erythropoietin in managing anemia in severe RDEB?

Answer 64

Erythropoietin can stimulate red blood cell production and is used when anemia does not respond to oral iron supplementation.

Question 65

What are the implications for dental care in JEB patients with hypoplastic enamel and oral candidiasis?

Answer 65

Dental care should focus on preventing tooth decay and managing mucosal blistering. Regular dental check-ups and antifungal treatments may be necessary.

Question 66

What is the likely cause of dilated cardiomyopathy in severe RDEB, and how should it be managed?

Answer 66

Dilated cardiomyopathy is likely caused by chronic anemia. Management includes treating anemia with recombinant EPO or transfusions.

Question 67

What laboratory tests and treatments are indicated for anemia of chronic disease in severe RDEB?

Answer 67

Tests include serum iron and erythropoietin levels. Treatments may involve recombinant EPO and blood transfusions.

Question 68

What preventive measures can be taken to protect the eyes in patients with JEB who have developed corneal erosions?

Answer 68

Preventive measures include using moisture chambers, ocular lubricants, and avoiding trauma to the eyes.

Question 69

What surgical intervention may be necessary for recurrent esophageal strictures in severe RDEB?

Answer 69

Esophageal dilation may be necessary, though recurrence is common.

Question 70

What additional diagnostic tests should be performed for severe RDEB patients with anemia unresponsive to oral iron?

Answer 70

Tests should include serum erythropoietin levels and a complete blood count to assess the severity of anemia.

Question 71

What psychological aspects should be addressed in the management of chronic pain in severe RDEB?

Answer 71

Management should include identifying warning signs of depression and providing support for chronic pain.

Question 72

What dietary modifications can help manage esophageal strictures in severe RDEB?

Answer 72

Dietary modifications include increased fluid and fiber intake and the use of stool softeners to manage constipation.

Question 73

What should caregivers identify in relation to depression?

Answer 73

Caregivers should identify warning signs of depression.

Question 74

What support strategies can caregivers provide for individuals with depression?

Answer 74

Provide emotional support and encourage open communication about feelings. Facilitate access to mental health resources and counseling.

Question 75

What are the potential cardiovascular complications associated with severe forms of EB?

Answer 75

Severe forms of EB can lead to dilated cardiomyopathy, a potentially fatal complication associated with chronic anemia.

Question 76

What management strategies are recommended for dilated cardiomyopathy in EB?

Answer 76

Regular monitoring of cardiac function. Addressing anemia through transfusions or EPO treatment as necessary.

Question 77

What are the current treatments indicated for Dystrophic Epidermolysis Bullosa (DEB)?

Answer 77

Tetracycline and phenytoin are not currently indicated treatments for DEB. However, Losartan is used to reduce fibrosis accompanying DEB wounding by reducing TGF-B expression in the skin.

Question 78

What is the significance of allogeneic bone marrow transplantation in RDEB?

Answer 78

Allogeneic bone marrow transplantation performed on RDEB noted collagen VII staining at the DEJ for 1 year or longer; however, restoration of anchoring fibrils was incomplete. There is a 30% mortality rate due to widespread cutaneous erosions and the need for immunosuppression for successful transplant.

Question 79

What are the outcomes of autologous genetic therapies in RDEB?

Answer 79

Autologous genetic therapies include retroviral ex vivo gene therapy using autologous keratinocytes. After 6.5 years of postgrafting, grafts showed positive expression of laminin 332 and resistance to blistering. Restoration of collagen VII expression and anchoring fibril formation can last for as long as 1 year.

Question 80

What are the characteristics of Hallopeau Siemens EB?

Answer 80

Hallopeau Siemens EB presents with generalized blistering in infancy, extensive denudation of skin at birth, healing and blistering cycles leading to intermittent scarring, and pseudosyndactyly resulting from skin closure. SCC can develop in 50-80% of cases, leading to metastatic disease.

Question 81

What are the key features of Kindler syndrome?

Answer 81

Kindler syndrome features include EB-like trauma-induced blistering at birth, progressive poikiloderma in adulthood, and photosensitivity. A consistent feature is the reduplication of the basement membrane, along with decreased expression of kindlin 1 KIND 1.

Question 82

What ocular features are associated with RDEB and JEB?

Answer 82

Common ocular features seen in both RDEB and JEB include corneal ulcerations with scarring. However, obliteration of tear ducts is not typically associated with these conditions.

Question 83

What are the potential benefits and risks of allogeneic bone marrow transplantation for a patient with severe RDEB?

Answer 83

Benefits include collagen VII staining at the dermal-epidermal junction for up to a year. Risks include a 30% mortality rate due to widespread cutaneous erosions and immunosuppression.

Question 84

What novel treatment has been found to reduce blister formation in EBS with inflammatory skin phenotypes?

Answer 84

Diacerain, an interleukin B blocker derived from rhubarb root, has been found to reduce blister formation in EBS with inflammatory skin phenotypes.

Question 85

What outcomes have been observed with retroviral ex vivo gene therapy using autologous keratinocytes in RDEB?

Answer 85

Outcomes include positive expression of laminin 332 and resistance to blistering for up to 6.5 years post-grafting.

Question 86

What are the implications of using Losartan in the treatment of Dystrophic Epidermolysis Bullosa (DEB)?

Answer 86

Losartan is used to reduce fibrosis accompanying DEB wounding by decreasing the expression of TGF-B in the skin, which may help improve healing and reduce scarring.

Question 87

What are the potential outcomes and risks associated with allogeneic bone marrow transplantation in patients with RDEB?

Answer 87

Allogeneic bone marrow transplantation in RDEB can lead to collagen VII staining at the DEJ for 1 year or longer; however, there is a 30% mortality rate due to widespread cutaneous erosions and the need for immunosuppression, which is critical for the success of the transplant.

Question 88

How does gene editing via CRISPR/Cas9 represent a promising future therapy for patients with Epidermolysis Bullosa?

Answer 88

Gene editing via CRISPR/Cas9 combined with induced pluripotent stem cells offers a potential future therapy for Exon skipping, which may help restore normal function in patients with genetic forms of Epidermolysis Bullosa.

Question 89

What ocular features are commonly associated with RDEB and JEB, and which feature is not typically seen in both?

Answer 89

Common ocular features in RDEB and JEB include corneal ulcerations with scarring. However, obliteration of tear ducts is not typically seen in both conditions.

Question 90

What are three steps in the diagnosis of Epidermolysis Bullosa (EB)?

Answer 90

1. Review of systems: Assess gastrointestinal, respiratory, ocular, or growth abnormalities. 2. Physical exam: Look for scarring, atrophy, or milia, and examine nails, eyes, mucosa, hair, and teeth. 3. Biopsy: Conduct high-resolution microscopy to confirm diagnosis and rule out other disorders.

Question 91

What is the primary goal in the treatment of Epidermolysis Bullosa (EB)?

Answer 91

The primary goal in the treatment of EB is to support wound care and nutrition, instruct families, and manage complications such as infections, anemia, and extraneous diseases through a multidisciplinary approach.

Question 92

What are the clinical manifestations of Epidermolysis Bullosa Simplex (EBS)?

Answer 92

EBS is characterized by sudden onset of grouped or herpetiform blisters, extensive erosions, nail shedding, and dystrophy of palmoplantar hyperkeratosis in older children.

Question 93

What is the age of onset for Generalized Intermediate Epidermolysis Bullosa (EIB)?

Answer 93

The age of onset for Generalized Intermediate EIB is at birth.

Question 94

What are the sequelae and complications associated with Junctional Epidermolysis Bullosa (JEB)?

Answer 94

JEB can lead to extensive blistering, perioral granulation tissue, tracheal stenosis or obstruction, failure to thrive, and sepsis.

Question 95

How does Localized Dystrophic Epidermolysis Bullosa (DDEB) present clinically?

Answer 95

Localized DDEB presents with blisters, nail dystrophy, or nail loss, typically localized to sites of trauma such as knees, sacrum, and acal areas.

Question 96

What are the clinical manifestations of Severe RDEB?

Answer 96

Severe RDEB is characterized by extensively denuded skin, enamel pitting with caries, and loss of teeth, along with potential for pseudostangulation and flexion contractures of hands and limbs.

Question 97

How does the distribution of Generalized Intermediate Epidermolysis Bullosa (EIB) differ from Localized Epidermolysis Bullosa (LEB)?

Answer 97

Generalized Intermediate EIB is most prominent on hands, feet, and extremities with mild oral mucosal involvement, while LEB is localized (most often on hands, feet, and peritibial regions) with minimal oral mucosal involvement.

Question 98

What are the clinical manifestations of Dystrophic Epidermolysis Bullosa (DEB) in its localized form?

Answer 98

Localized DEB is characterized by blisters, nail dystrophy, or nail loss that may be presenting symptoms, typically localized early in life to sites of trauma.

Question 99

What complications can arise from Severe Hereditary Epidermolysis Bullosa (HREB)?

Answer 99

Severe HREB can lead to extensively cleaned skin, enamel pitting with caries, loss of teeth, and complications such as pseudostangulation, flexion contractures of hands and limbs, and malnutrition.