Mermaid Syndrome, or Sirenomelia

This is a rare and fatal congenital malformation characterized by the partial or complete fusion of the lower limb structures forming a single lower limb instead of  two.

Originally described by Rocheus in 1542 and Palfyn in 1953 and named after the mythical Greek Goddesses "Sirens".
Sirenomelia or Mermaid syndrome was initially claimed by some authorities to be the most severe form of "Caudal Regression syndrome" which was first  described by Duhamel  (1961), Until recently when Stevenson et al described it as a result of "Vascular Steal".

Mermaid Syndrome / Sirenomelia (Picture Credit ; Scialert )

The prevalence has been estimated at about 0.8-1 in 100,000 birth and as at now about 300 cases reported in the literature.
It has a male : female ratio of 2.7-3 : 1, and is more common in one of identical twins.

Features of Mermaid syndrome include:

• A single lower extremity,
• No feet (ectromelic mermaid), one foot (monopode mermaid) or both feet (sympode mermaid), which may be rotated externally.
• Sacrum is partially or completely absent,
• The femur may be Single (most commonly) or partially divided,
• Single umbilical artery,
• Absent or ambiguous external genitalia,
• Absent or imperforate anus,
• Renal anomalies.

Risk Factors
Maternal diabetes (16 – 22%)
Monozygotic Twin (15%)
Genetic factors;  as in autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA).
Extremes of temperature,
Radiations,
Drugs (lithium, sulfamides)
Organic solvents (xylene, trichloroethylene, methylchloride and acetone)

Pathogenesis
In Mermaid Syndrome, the umbilical cord forms a single artery instead of two arteries, leading to insufficient blood supply to the fetus; (A vascular steal phenomenon causing severe ischemia to the caudal portion of the fetus). Suffering malnutrition, the fetus fails to develop two separate limbs.


Types
Tocker and Heifetz classified the leg abnormalities into Types I through VII.
Type I is the least severe with all bones present; and Type VII, most severe, consisting of a lower extremity with a fused femur and absent tibia and fibula.

Diagnosis
Prenatal ultrasonography as early as 13 weeks of pregnancy can detect gross structural anomalies, presence of a single umbilical artery, presence of oligohydramnios etc.
If legalized in your country, following a prenatal ultrasound Diagnosis, termination of pregnancy could be considered in appropriate situations .

Differentials
Caudal Regression Syndrome
VATER association

Complications
Urogenital complications (renal agenesis, absent or ambiguous external genitalia )
Gastrointestinal complications ( tracheo-esophageal atresia, imperforate anus, etc )
Cardiopathy,
Musculoskeletal complications.

Prognosis
Being often fatal, the condition is incompatible with life; some are stillbirth while others rarely survive longer than a few days.
However, The some without renal agenesis may survive past infancy. The oldest surviving patient with mermaid syndrome is Tiffany Yorks (1988- date) after series of surgery.

Mermaid Syndrome (Picture Credit; pixshark)

NOTES

1. I.D.Young,MD,MRCP, K. M. O’Reilly,MB,ChB, MRC Path, C. H. Kendall, MB,ChB, I986,  ETIOLOGICAL HETEROGENEITY IN SIRENOMELIA,  Pediatric Pathology, 5:31-43, Copyright 1986 by Hemisphere Publishing Corporation (HINARI)

2. Jocelyn H. Bruce, Rita L. Romaguera, Maria M. Rodriguez, Víctor H. González-Quintero, and E. Michel Azouz ,2009,CAUDAL DYSPLASIA SYNDROME AND SIRENOMELIA: ARE THEY PART OF A SPECTRUM? Informa Healthcare Journal Vol. 28, No. 3 , Pages 109-131 (doi:10.1080/15513810902772383)  (HINARI)

3. Marybeth Browne MD1, Philip Fitchev MD2, Brian Adley MD2 and Susan E Crawford MD, 2004 , Sirenomelia with an Angiomatous Lumbosacral Myelocystocele in a Full-term Infant, Journal of Perinatology (2004) 24, 329–331. 

4.  Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier

5. Reddy KR, Srinivas S, Kumar S, Reddy S, Hariprasad, Irfan GM. Sirenomelia a rare presentation. Journal of Neonatal Surgery. 2012;1:7.

6. Stevenson RE, Jones KL, Phelan MC, Jones MC, Barr M, Jr, Clericuzio C. Vascular steal: The pathogenetic mechanism producing sirenomelia and associated defects of the viscera and soft tissues. Pediatrics. 1986;78:451–7

7. Vinayak Y. Kshirsagar, Minhajuddin Ahmed, and Sylvia M. Colaco, 2012 , Sirenomelia Apus: A Rare Deformity Journal of Clinical Neonatology. 2012 Jul-Sep; 1(3): 146–148.

8.  Z.Kokrdova  Caudal regression syndrome, Journal Of Obstetrics and Gynecology (1983) 4,101-102   DOI: 10.3109/01443615.2012.743508 (HINARI)

Werewolf syndrome, Ambras syndrome or Hypertrichosis

This is an extremely rare condition with excessive hair growth over and above the normal for the age, gender and race of an individual.It can be generalized or localized, congenital or acquired.

Werewolf Syndrome (Picture Credit; reddit)

First documented by Aldrovandus In 1648

The gender and racial prevalence for this condition is not yet known as Less than 100 cases have been reported worldwide, with an incidence of about 1 in a billion to 1 in 10 billion (congenital hypertrichosis lanuginosa).
It is apparent at birth (depending on the type).

Hypertrichosis differs from Hirsutism in that, it is not androgen related and does not follow the male pattern of Hair distribution, while Hirsutism commonly occurs in women and presents as androgen-induced male pattern hair growth.

Classification
Congenital
• Hypertrichosis lanuginosa: completely covered in thin lanugo hair; long, silky and light colored hairs
• Generalised hypertrichosis: involves vellus and terminal hairs.
• Terminal hypertrichosis:  coarser and thicker hairs and usually pigmented, accompanied by gingival hyperplasia.
• Circumscribed hypertrichosis; presence of thick vellus hair on the upper extremities ( e.g hairy eyebrows )
• Localised hypertrichosis,
• Nevoid hypertrichosis; excessive terminal hair and is usually not related to any diseases.

Acquired
• Hypertrichosis lanuginosa; fine and unpigmented hair on the face, trunk and armpit.
• Generalised hypertrichosis:
• Patterned hypertrichosis: increase in hair growth in a pattern formation
• Localised hypertrichosis: increase in hair density and length often secondary to irritation or trauma



Causes
Congenital
Genetically acquired; autosomal dominant mutation on 8q (Hypertrichosis lanuginosa),autosomal dominant mutation on chromosome x24-q27.1 (Generalized hypertrichosis), mutation in MAP2K6 on chromosome 17 (Terminal hypertrichosis).

Acquired

• Cancer,
• Endocrinopathies; hyperthyroidism
• Metabolic disorders such as porphyria cutanea tarda
• Anorexia nervosa
• Medications; iodine, psoralens, minoxidil, steroids,cyclosporine, diazoxide,phenytoin, streptomycin, hexachlorobenzene, penicillamine, heavy metals, sodiumtetradecyl sulfate, acetazolamide, and interferon.
•  Minor abrasions or injury requiring a plaster cast
• Longstanding lichen simplex, infections and vaccinations.
• Head injuries, malnutrition, starvation and AIDS (are less common causes)

Diagnosis
 This is mainly clinical, however, hair biopsy for histologic classification is indicated; Lanugo hairs tend to be non-pigmented,  Vellus hair may be pigmented or nonpigmented. Lanugo and vellus hairs can be difficult to distinguish at histological examination.

Differential diagnosis
Hirsutism
Mucopolysaccharidoses Types I-VII
Rubinstein-Taybi Syndrome


Treatment
Drugs; Eflornithine (Vaniqa cream), Has been found to be very useful.
           Bleaching can improve congenital hypertrichosis lanuginosa (CHL) patients’ appearance.
           Antidepressants can be used in patients with depression.
Physical depilation; tweezing or plucking, shaving, and waxing. Tweezing is an effective temporary hair removal method, but it is a slow, tedious, and painful process.
Chemical depilatories; contain sulfides, thioglycolates, and enzymatic depilatory agents. They break down hair by cleaving its cysteine linkages thereby causing minimal damage to the underlying skin. Electrolysis,
Intense pulsed light therapy
Diathermy and Radiation therapy can be used rarely

Hypertrichosis (Picture Credit; real world image.)

Surgical Care
    Laser hair removal has been proposed as a treatment option, although it is still remains controversial.


NOTES

1. Beighton P. Congenital hypertrichosis lanuginosa. Arch Dermatol. Jun 1970;101(6):669-72.

2. Klein  AWRish  DC Depilatory and shaving products. Clin Dermatol. 1988;668- 70

3. Lesiewicz  JGoldsmith  LA Antizyme release is an early event in ornithine decarboxylase induction by hair plucking. J Invest Dermatol. 1983;8097- 100

4. Hynd  PINancarrow  MJ Inhibition of polyamine synthesis alters hair follicle function and fiber composition. J Invest Dermatol. 1996;106249- 253

5. Medical Dictionary; Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved

6. Medscape; eMedicine.

7. Partridge JW. Congenital hypertrichosis lanuginosa: neonatal shaving. Arch Dis Child. Jun 1987;62(6):623-5

8. Tadin M, Braverman E, Cianfarani S, et al. Complex cytogenetic rearrangement of chromosome 8q in a case of Ambras syndrome. Am J Med Genet. Jul 22 2001;102(1):100-4.

9. Wikipedia | hypertrichosis

Broken Heart Syndrome or Takotsubo Cardiomyopathy

Is a sudden temporary weakening of the muscular portion of the heart (Myocardium) triggered by physical or emotional stress such as;  a break-up, the death of a loved one, constant anxiety etc.

Also known as "transient apical ballooning syndrome", "apical ballooning cardiomyopathy", "stress-induced cardiomyopathy", "Gebrochenes-Herz-Syndrome", and "stress cardiomyopathy" "

Broken heart syndrome is a recently recognized heart problem. It was first described in Japan 1990, by Sato  a cardiovascular specialist.
The hallmark bulging out of the apex of the heart with preserved function of the base earned the syndrome its name "tako tsubo", meaning "Octopus trap" in Japan.

It is very Common among the Asian or Caucasian; 57.2% in Asian, 40% in Caucasian, and 2.8% in other races.

Literature reviews report a mean patient age of 67 years, although cases of TCM have occurred in children and young adults.
It is commoner in women than in men, Nearly 90% of reported cases involve postmenopausal women.
Studies reported that 1.7-2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy (TCM).

Signs and Symptoms
Similar symptoms to patients with a heart attack including;

• sudden, intense chest pain
• shortness of breath,
• sometime palpitations, nausea, vomiting, syncope, and rarely, cardiogenic shock have been reported.
• low blood pressure
• congestive heart failure (sudden Onset).

One of the more unique features of TCM is its association with a preceding emotionally or physically stressful trigger event, occurring in approximately two thirds of patients. Unlike acute coronary syndrome, in which peak occurrence is during the morning hours, TCM events are most prevalent in the afternoon, when stressful triggers are more likely to take place.

Risk Factors
Stressors include;

• Break up or physical separation
• divorce,
• betrayal or romantic rejection.
• arguing with a spouse
• death of a loved one
• fear from public speaking
• bad financial news
• legal problems
• natural disasters
• motor vehicle collisions
• exacerbation of a chronic medical illness,(Acute asthma, stroke etc)
• newly diagnosed, significant medical condition
• surgery
• an intensive care unit stay
• the use of or withdrawal from illicit drugs.
• chemotherapy
• It has also been reported after near-drowning episodes
• It could even happen after a good shock (like winning the lottery or a surprise party)

Hormonal;
Lack of estrogen as seen in postmenopausal women

Genetic factors;
Susceptibility to TCM in individuals may be partially related to genetic factors; L41Q  polymorphism of G protein coupled receptor kinase (GRK5) which responds to catecholamine stimulation and attenuates the response of beta-adrenergic receptors

Following a stressful event, it is believed that in Patients with broken Heart syndrome there is Increase sympathetic drive ("fight or flight" mechanism) as a result of cathecholamine mediated cardiotoxicity, which results in multi-vessle epicardial coronary artery spasm, microvascular dysfunction or spontaneous aborted myocardiac infaction.

Diagnosis

• An electrocardiogram (ST-segment elevation and T-wave inversion)
• Cardiac enzymes (troponin I and T, are elevated in 90% of patients)
• An echocardiogram (hypokinesis or akinesis of the midsegment and apical segment of the left ventricle),
• An angiogram (completely normal coronary arteries)
• Chest radiographs are often normal, but they may demonstrate pulmonary edema.
• Cardiac magnetic resonance imaging may be a diagnostic modality uniquely suited for establishing the diagnosis of TCM by accurately visualizing regional wall motion abnormalities, quantifying ventricular function, and identifying reversible injury to the myocardium by the presence of edema/inflammation and the absence of necrosis/fibrosis.

Mayo Clinic criteria for diagnosis of TCM can be applied to a patient at the time of presentation and must contain all 4 aspects:

1. Transient hypokinesis, dyskinesis, or akinesis of the left ventricular mid segments, with or without apical involvement; the regional wall-motion abnormalities extend beyond a single epicardial vascular distribution, and a stressful trigger is often, but not always, present 
2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.
3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin level
4. Absence of pheochromocytoma or myocarditis

Differential Diagnosis
    Acute Coronary Syndromes
    Angina Pectoris
    Aortic Dissection
    Boerhaave Syndrome
    Cardiac Tamponade
    Cardiogenic Shock
    Cardiomyopathy, Cocaine
    Cardiomyopathy, Dilated
    Cardiomyopathy, Hypertrophic
    Coronary Artery Vasospasm

Complications
Pulmonary edema.

Hypotension.
Arrhythmias (irregular heartbeats).
Treatment
The treatment of takotsubo cardiomyopathy is generally supportive in nature.
Standard therapies, such as the following, may be indicated:
    Aspirin
    Beta blockers
    Nitrates
    Heparin or enoxaparin
    Platelet glycogen (GP) IIb/IIIa inhibitors
    Morphine
    Clopidogrel

Patients in acute congestive heart failure may require diuresis, and patients with cardiogenic shock may require resuscitation with intravenous fluids and inotropic agents.

The insertion of an intra-aortic balloon pump has also been reported as being a successful resuscitative intervention, due to left ventricular outflow obstruction that can result from a hyperkinetic basal segment and dyskinetic apex. Fluids and beta blockers, or calcium channel blockers, are beneficial in this situation, whereas inotropes may exacerbate the problem and should be used with caution.

Dysrhythmias and cardiopulmonary arrest should be treated using current advanced cardiac life support (ACLS) protocols. Although thrombolytics will not benefit patients with takotsubo cardiomyopathy (TCM), their use should not be withheld when percutaneous coronary intervention (PCI) is not available and patients otherwise meet criteria.

While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. It is important that the individual stay physically healthy, while learning and maintaining methods to manage stress, and cope with future difficult situations.

Prevention
There's a small chance that broken heart syndrome can happen again after a first episode.
There's no proven therapy to prevent additional episodes; however, many doctors recommend long-term treatment with beta blockers or similar medications that block the potentially damaging effects of stress hormones on the heart. Recognizing and managing stress in your life also is very important.




NOTES

1. Bergman BR, Reynolds HR, Skolnick AH, Castillo D (August 2008). "A case of apical ballooning cardiomyopathy associated with duloxetine". Ann. Intern. Med. 149 (3): 218–9

2. Eshtehardi P, Koestner SC, Adorjan P, Windecker S, Meier B, Hess OM, Wahl A, Cook S (July 2009). "Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population". Int. J. Cardiol. 135 (3): 370–5.

3. Gianni, M, Dentali F et al. (December 2006). "Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review". European Heart Journal (Oxford University Press) 27 (13): 1523–1529.

4. Kawai S, Kitabatake A, Tomoike H. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ J. Jun 2007;71(6):990-2

5. Medscape | article/1513631

6. Mayo Clinic | broken heart syndrome basics

7. Sato H, Tateishi H, Uchida T, et al. Kodama K, Haze K, Hon M, eds. Clinical Aspect of Myocardial Injury: From Ischaemia to Heart Failure. Tokyo: Kagakuhyouronsya; 1990:56-64.

8. Sharkey SW, Lesser JR, Garberich RF, Pink VR, Maron MS, Maron BJ. Comparison of Circadian Rhythm Patterns in Tako-tsubo Cardiomyopathy Versus ST-Segment Elevation Myocardial Infarction. Am J Cardiol. May 29 2012

9. Wikipedia | Takotsubo cardiomyopathy

10. World Journal Of Cardiology | Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment.

11. Zamir, M (2005). The Physics of Coronary Blood Flow. Springer Science and Business Media. p. 387. ISBN 978-0387-25297-1.

Butterfly Children Or Epidermolysis Bullosa (EB)

This is any of a group of inherited chronic noninflammatory skin diseases in which large blisters and erosion develop after slight trauma, Blistering often appears in infancy in response to simply being held or handled. In rarer forms of the disorder, EB can be life-threatening. There is no cure for the disorder. Treatment focuses on preventing and treating wounds and infection. Also called Cotton Wool Babies or Crystal Skin Children

It was first described in 1870 by Ferdinand Ritter von Hebra;  an Austrian physician and dermatologist known as the founder of the New Vienna School of Dermatology, an important group of physicians who established the foundations of modern dermatology.

Epidermolysis bullosa (Picture Credit; dermamin)

A very rare genetic connective tissue disorder that affects about 1 child out of every 20,000- 50,000 births worldwide
The disorder occurs in every racial and ethnic group throughout the world and affects both sexes

Signs and Symptoms

•   Fluid-filled blisters on the skin, especially on the hands and feet due to friction

•   Deformity or loss of fingernails and toenails

•   Internal blistering, including on the vocal cords, esophagus and upper airway( resulting in Hoarse cry, cough, or other breathing problems)

•   Skin thickening on the palms and the soles of the feet

•   Scalp blistering, scarring and hair loss (scarring alopecia)

•   Thin-appearing skin (atrophic scarring)

•   Tiny white skin bumps or pimples (milia)

•   Dental problems, such as tooth decay from poorly formed enamel

•   Blisters in or around the mouth and throat resulting in Difficulty swallowing (dysphagia)

•   Blisters around the eyes and nose

•   Blisters on the skin as a result of minor injury or temperature change

•   Blistering that is present at birth

Epidermolysis bullosa blisters may not appear until a toddler first begins to walk or until an older child begins new physical activities that trigger more intense friction on the feet.

Types
4 major types and 30 different subtypes have been described based on the precise ultra structural level at which the split responsible for blistering occurs.
The major types include;

•  Epidermolysis bullosa simplex (EBS) ; Epidermolytic

•  Junctional epidermolysis bullosa (JEB) ; Lucidolytic

•  Dystrophic epidermolysis bullosa (DEB) ; Dermolytic

•  Kindler syndrome; Mixed type

François Henri Hallopeau, a french dermatologist, described the Dystrophic type and seperated it from Simplex type in 1898
Junctional EB was described by Herlitz in 1935

Causes

The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers that prevent them from moving independently from one another (shearing).
In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even only minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.
Furthermore, as a complication of the chronic skin damage, people suffering from EB have an increased risk of malignancies (cancers) of the skin.
More than 1000 mutations, encompassing more than 10 structural genes, have now been documented concerning Epidermolysis Bullosa.
    The Genetic Mutations of structural proteins of the epidermis
EBS;
Intraepidermal tonofilaments - Keratin 5, 14 (autosomal dominant disorders)
Junctional EB
Intralamina lucida - anchoring filaments and hemidesmosome, laminin 5, BP Ag 2, α6β 4 integrin (autosomal recessive disorder)
Dystrophic EB
Sublamina densa - anchoring fibrils, collagen VII ( autosomal dominant or autosomal recessive ).

Investigations/Diagnosis
Prenatal testing
Transmission electron microscopy
Immunofluorescence mapping (IFM)
Mutation analysis
Electron microscopy


Differential Diagnosis
Thermal Burns

 Complications

• Infection

• Sepsis

• Deformities; fusion of fingers or toes and abnormal bending of joints (contractures), such as those of the fingers, knees and elbows.

• Malnutrition and anemia. Blisters in the mouth can make eating difficult and lead to malnutrition. This may lead to anemia, delayed wound healing or, in children, slowed growth.

• Dehydration. Large, open blisters can cause loss of body fluid that leads to severe dehydration.

• Constipation due to painful blisters in the anal area. It can also be caused by not ingesting enough liquids or high-fiber foods, such as fruits and vegetables.

• Eye disorders. Inflammation of the eye can harm the clear covering over the eye (cornea) and, sometimes, cause blindness.

• Skin cancer; squamous cell carcinoma.

• Death. Infants with a severe form of junctional epidermolysis bullosa are at high risk of infections and loss of body fluids from widespread blistering. Their survival also may be threatened because of blistering, which may hamper their ability to eat and breathe. Many of these infants die in childhood.

Treatment
Presently, there is no cure for EB.
The treatment of epidermolysis bullosa (EB) is primarily preventive and supportive
Prevent Blisters
    Avoid getting too hot by keeping rooms at an even temperature
    Apply lotion to the skin to reduce friction and keep the skin moist
    Wear soft clothing
    Use sheepskin on car seats and other hard surfaces
    Wear mittens at bedtime to help prevent scratching.

Treating Blisters
    Reduce pain or discomfort
    Prevent loss of body fluid
    Promote healing
    Prevent infection.
    Safely break a blister in its early stages; punctured with a sterile needle or a blade. This may prevent the accumulation of fluid and pressure and may thus prevent the blister from extending. Complete and gentle drainage of the fluid, accomplished by leaving the roof of the blister intact and by covering the affected area with white petrolatum–impregnated gauze, helps to promote an environment most optimal for healing. If the blister repeatedly refills with fluid, it should be drained several times.
    Prescribing a mild painkiller so that changing bandages won’t hurt as much
    Recommending special bandages that will help the blisters to heal, lessen the pain, and prevent infection.

Treating Infection
    A soaking solution
    An antibiotic ointment; daily application of polymyxin, bacitracin, or silver sulfadiazine topical ointments to treat open or partially healed wounds,Gentamicin soaks (480 mg/L saline), acetic acid soaks (white vinegar), and the addition of small amounts of bleach to the bath water (eg, 1/8 cup per full tub) have been used to decrease the overgrowth of pseudomonas and staphylococcal organisms.
    An oral antibiotic to reduce the growth of bacteria
    A special wound covering (for sores that don’t heal).

Treating Epidermolysis bullosa (Picture Credit: nhs)

Preventing Nutritional Problems
In some people with EB, blisters may appear in the mouth and esophagus, making it hard to chew and swallow. Over time, this may lead to nutritional problems. Because nutrition is so important for proper growth and development, it is important that children with EB eat well. Here;
    Feed the baby using a bottle with a special nipple, an eyedropper, or a syringe.
    When the baby is old enough to take in food, add extra liquid to finely mashed food to make it easier to swallow.
    Give the baby soups, milk drinks, mashed potatoes, custards, and puddings.
    Never serve food that is too hot.
Dietitians can help anyone with EB by:
    Providing recipes for food that is nutritious and easy to eat
    Suggesting nutritional supplements;Vitamin and iron supplements are advised if nutritional compromise is present
    Recommending diet changes to prevent stomach or intestinal problems; a blenderized diet is recommended

Surgery
Esophageal dilatation or insertion of a gastrostomy tube may be required if esophageal strictures develop.
Patients with limited donor sites for a skin graft may need advanced therapy with bioengineered skin products eg, composite cultured skin (CCS), Graftskin, Dermagraft
Surgical intervention for contractures.


Intensive studies are underway to find better ways to treat and relieve the symptoms of epidermolysis bullosa, including:
    Gene therapy
    Bone marrow transplantation
    Protein replacement therapies
    Cell-based therapies


Prognosis
Mild forms of epidermolysis bullosa improve with age.Very serious forms of epidermolysis bullosa have a very high mortality rate.

NOTES;

1. DEBRA | what is eb

2. Dermapath | Epidermolysis Bullosa

3. Fine JD, Mellerio JE. Epidermolysis Bullosa. In: Bolognia JL, Jorizzo JL, Schaffer JV, et al, eds.Dermatology. 3rd ed. Philadelphia, Pa:Mosby Elsevier; 2012:chap 32

4. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50

5. [Guideline] Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50

6. Mayo Clinic | epidermolysis bullosa

7. Medical Dictionary; The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company.

8. Medscape | article; 909549

9. National Institute Of Arthritis And Musculoskeletal Disease | epidermolysis bullosa

10. Okoye BO, Parikh DH, Buick RG, Lander AD. Pyloric atresia: five new cases, a new association, and a review of the literature with guidelines. J Pediatr Surg. Aug 2000;35(8):1242-5

11. Roddy Isles, Head of Press (2005-05-12). "Dundee Scientists on road to cure for "Butterfly Children" condition". University of Dundee.

12. Suellen Hinde, Health reporter (2006-11-26). "Little girl's life of pain". HeraldSun.com.au.

Ice Cream Headache or Sphenopalatine Ganglioneuralgia

Sphenopalatine Ganglioneuralgia (nerve pain of the sphenopalatine ganglion).

 A migraine triggered by eating cold foods (oropharyngeal irritation due to cold foods), the ingestion of which may cause bi-frontal headaches in Patients with migraines. Also known as brain freeze, cold-rush, cold-stimulus headache particularly following quick consumption of cold beverages or foods such as ice cream and ice pops.

(Picture credit ; visualize us)

The term "ice-cream headache" has been in use since 31 January 1937, contained in a journal entry by Rebecca Timbres
The first published use of the term "brain freeze", as it pertains to cold-induced headaches, was on 27 May 1991

And although you may feel pain, it's not dangerous and doesn't mean that anything is wrong in your body.
The ice cream headache passes quickly with a lovely rush of pain-killing endorphins cancelling out the pain.
   

  Symptoms

• Sharp, stabbing pain in the forehead

• Pain that peaks about 30 to 60 seconds after it begins

• Pain that rarely lasts longer than five minutes

 Classification
The International Classification of Headache Disorders (ICHD) code is 13.11.2 and International Statistical Classification of Diseases and Related Health Problems ICD-10NA code is G44.8021, "Headache attributed to ingestion or inhalation of a cold stimulus".

Risk Factors;
Ice cream headaches can affect anyone. But you may be more susceptible to ice cream headaches or have more-severe ice cream headaches if you're prone to migraines. The headaches may also be more common among people with a history of head injuries.
 

Cause
Theory 1
   When something cold touches the roof of your mouth (palate), the sudden temperature change of the tissue stimulates nerves to cause rapid dilation and swelling of blood vessels. This is an attempt to direct blood to the area and warm it back up. The dilation of the blood vessels triggers pain receptors, which release pain-causing prostaglandins, increase sensitivity to further pain, and produce inflammation while sending signals through the trigeminal nerve to alert the brain to the problem. Because the trigeminal nerve also senses facial pain, the brain interprets the pain signal as coming from the forehead. This is called 'referred pain' since the cause of the pain is in a different location from where you feel it. Brain freeze typically hits about 10 seconds after chilling your palate and lasts about half a minute. Only a third of people experience brain freeze from eating something cold, though most people are susceptible to a related headache from sudden exposure to a very cold climate.

An ice cream headache is the direct result of the rapid cooling and rewarming of the capillaries in the sinuses. A similar but painless blood vessel response causes the face to appear "flushed" after being outside on a cold day. In both instances, the cold temperature causes the capillaries in the sinuses to constrict and then experience extreme rebound dilation as they warm up again.

Theory 2
  The research, carried out in part by Harvard Medical School, used trans-cranial Doppler imaging to study blood flow in the brains of patients while they had ice cream headaches or brain freeze induced using iced water. They also performed the experiment with normal water as a control.

The results, which are being presented at the Experimental Biology 2012 conference, show that brain freeze is accompanied by a rapid dilation of the anterior cerebral artery, which floods the brain with blood and in turn causes pain. When the vessel constricts, patients report that the pain disappears. The researchers speculate that it's a form of self-defense for the brain:

    "The brain is one of the relatively important organs in the body, and it needs to be working all the time,... It's fairly sensitive to temperature, so vasodilation might be moving warm blood inside tissue to make sure the brain stays warm."
  

Brain Freeze (Picture credit; chemistry about)

They also explain that, because the skull is rigid, an increase in blood volume in the brain causes an increase in pressure, which is what induces the pain.

The researchers point out that similar blood flow alterations could be behind migraines and other types of headaches. If that's the case, targeting headaches with drugs that can specifically affect dilation of blood vessels could bring a lot of relief to an awful lot of people.

Prevention
• Slow down. Eating or drinking cold food slowly allows one's mouth to get used to the temperature.

• Hold cold food or drink in the front part of your mouth and allow it to warm up before swallowing.

• Head north. Brain freeze requires a warm ambient temperature to occur, so it's almost impossible for it to happen if you're already cold.



 

Treatment
It does not require any medical treatment, but relief can be gotten from one of these;
pressing the tongue against the roof of the mouth to warm the area or
tilting the head back for about 10 seconds.
drink a liquid that has a higher temperature than the substance that caused the ice cream headache.
breathing in through the mouth and out through the nose, thus passing warm air through the nasal passages.



NOTES;

1. Bird, N; MacGregor, EA; Wilkinson, MI (January 1993). "Ice cream headache—site, duration, and relationship to migraine". Headache 32 (1): 35–8.

2. "ICHD-II Abbreviated pocket version" (pdf). International Headache Society. 2004.

3. Gordon, Serena (February 2003). "The Scoop on Ice-Cream Headaches". Current Science 88 (13): 12

4. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004;24(suppl):9.

5. Jankelowitz, SK.; Zagami, AS. (Dec 2001). "Cold-stimulus headache.". Cephalalgia 21 (10): 1002.

6. Mayo Clinic | ice-cream-headaches

7. Mental floss | why do people get ice cream headaches

8. Medical News Today | articles; 244458.

9. Timbres, Harry; Timbres, Rebecca (1939). "We didn't ask Utopia: a Quaker family in Soviet Russia". Prentice Hall.

10. Wikipedia | Ice cream headache

Xeroderma pigmentosum ( XP Or Children of the Night )

Xeroderma pigmentosum, commonly known as XP Or Children of the Night
This is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight.
It is rare disorder transmitted in an autosomal recessive manner, characterized by excessive sensitivity to sunlight (photosensitivity),  pigmentary(skin colour) changes, premature skin aging, and malignant tumor development.
Formerly called DeSanctis-Cacchione syndrome.

Xeroderma Pigmentosa (Picture Credit; witbanknews.)

Was first described in 1874 by Hebra and Kaposi.

With an incidence of 1:250,000 in the United States,
                                  1:40,000 population in Japan, (roughly 6 times more common in Japanese                                                                people than in others)
                                   approximately 100 diagnosed cases in the UK.

Affects all races, and found to be more common in Japan, North Africa, and the Middle East.
Both sexes are equally affected.
Usually detected at age 1-2 years.

Cause
Caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems.
However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.
Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER)
When nucleotide excision repair (NER) enzymes undergo mutation, it leads to reduction in or elimination of NER and if this is unchecked, results in Mutation of the individuals cell DNA following exposure to ultraviolet light.

Patients who have XP, inherited two recessive xeroderma pigmentosum genes (one from each parent); If both parents are only carriers of the xeroderma pigmentosum trait (each have one xeroderma pigmentosum gene and one normal gene), they will not show signs or symptoms of the disease. By having the two xeroderma pigmentosum genes this causes the patients to have an extreme sensitivity to UV light and as a result experience a range of signs and symptoms of xeroderma pigmentosum.

There are 7 different types/groups of XP (XP-A to XP-G)


Signs and Symptoms
A history of severe persistent sunburn can be found in many patients.
no family history is present; the parents, being heterozygotes, are healthy.

XP (Picture Credit; dermaamin.)

 The disease usually progresses through 3 stages.

1.  The first stage occurs around 6 months after birth (skin appears normal at birth) with the following signs: Areas exposed to the sun such as the face show a reddening of the skin (diffuse erythema), scaling, and freckle like areas of increased pigmentation. appearing initially on the face. With progression of the disease, the skin changes appear on the lower legs, the neck, and even the trunk in extreme cases. While these  features tend to diminish during the months with decreased sun exposure, as time passes, these findings become permanent. Irregular dark spots may also begin to appear.

     2.  Continued sun exposure will lead to the second stage, which is characterized by poikiloderma.              This is where there are irregular patches of lightened or darkened skin        
           (mottled hyperpigmentation and hypopigmentation), a spider web-like collection of blood        spots and vessels are seen through the skin (telangiectasias) , and there is  thinning of the skin (skin atrophy).

     3. The third stage is the development of actinic keratoses and skin cancers (including squamous     cell carcinomas, malignant melanoma, basal cell carcinoma, and fibrosarcoma) . These may occur as early as age 4-5 years and are more prevalent in sun-exposed areas such as the face.

The photosensitivity in Xeroderma Pigmentosa maybe acute in nature (50% of cases).

Complications

Eye (Ocular) problems occur in nearly 80% of xeroderma pigmentosum patients.

    Eyes become painfully sensitive to the sun (photophobia).
    Eyes easily irritated, bloodshot and clouded. Conjunctivitis may occur.
    Non-cancerous and cancerous growths on the eyes may occur.(Eyelid solar lentigines,malignant melanoma, Ectropion, symlepharo,vascular pterygia, fibrovascular pannus etc)

Neurological problems occur in about 20% of xeroderma pigmentosum patients.

    These can be mild or severe and include;microcephaly, spasticity, poor coordination,developmental delay, deafness, and short stature. hyporeflexia, arefleixa, ataxia, chorea, segmental demyelination, sensorineural deafness, supranuclear ophthalmoplegia, and mental retardation. The neurologic problems might overshadow the cutaneous manifestations in some patients with xeroderma pigmentosum.
    May develop in late childhood or adolescence. Once they do occur they tend to worsen over time.


Diagnosis;
An eye exam may show:
    Clouding of the cornea
    Keratitis
    Lid tumors
    Blepharitis
The following tests can help diagnose the condition in a baby before the birth:
    Amniocentesis
    Chorionic villous sampling
    Culture of amniotic cells
The following tests can help diagnose the disorder after the birth of the child:
    Culture of skin fibroblasts
    Skin biopsy

Differential Diagnosis
Acute Lupus Erythematosus
Ataxia-Telangiectasia
Bloom Syndrome
Congenital erythropoietic porphyria
Cockayne's syndrome
Fanconi anemia
Hartnup disease
LEOPARD Syndrome


Treatment
   Prevention is the most important part of treatment here.Restricting outdoor activities to night time,

Sunscreen for XP (Picture Credit; look for diagnosis.)

•    Sunscreens; Physical sunscreens (protective clothing, hats, eyewear))which scatter and reflect  radiation. They contain large particles,such as titanium dioxide, zinc oxide, red ferric oxide,  talc and kaolin .  Chemical sunscreens absorb UV radiation; PABA esters, salicylates, and cinnamates, mainly block UV-B. Broad-spectrum chemical sunscreens include a combination of ingredients designed to block both UV-B and UV-A.

•    Genetic counseling

       Support and counseling for patients and families, because of the severe lifestyle restrictions
             involved.

•     Avoid smoking, because cells from individuals with XP are also hypersensitive to environmental mutagens, such as benzo(a)pyrene found in cigarette smoke.

  Drug;

•     Vitamin D supplements may be needed, since sunlight (a major source of vitamin D) is excluded.

•     Emollients for dry skin.

•     Artificial tears for dry eyes.

•     Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum

•     5-fluorouracil may be useful for actinic keratose

•     A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme into the skin by means of specially engineered liposomes

•     Gene therapy for xeroderma pigmentosum is still in a theoretical and experimental stage.

Surgery;
     The malignancies associated with xeroderma pigmentosum should be completely excised.



Prognosis;
Less than 40% of individuals with the disease survive beyond the age of 20. Some XP victims with less severe cases do manage to live well into their 40s.

NOTES;
1. Alapetite C, Benoit A, Moustacchi E, Sarasin A. The comet assay as a repair test for prenatal diagnosis of Xeroderma pigmentosum and trichothiodystrophy. J Invest Dermatol. Feb 1997;108(2):154-9

2. DermaNet NZ | xeroderma pigmentosum.

2. Hoesl M, Dietz K, Rocken M, et al; Vitamin D levels of XP-patients under stringent sun-protection. Eur J Dermatol. 2010 Jul-Aug;20(4):457-60. Epub 2010 May 21

  
3. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. Feb 1987;123(2):241-50

4. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. Jun 23 1988;318(25):1633-7

5. Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet J Rare Dis 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607.

6. Lim HW, Hawk JLM. Photodermatologic disorders. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa: Elsevier Saunders; 2012:chap 87.

7. Medical Biochemistry at a Glance. John Wiley & Sons. 28 November 2011. ISBN 1118292405.

8. Mescape; | article 1119902

9. Nouspikel T. Nucleotide excision repair and neurological diseases. DNA Repair (Amst). Jul 1 2008;7(7):1155-67

10. Schadt C, Fine JD. Genetic disorders predisposing to skin malignancy. In: Rigel DS, Robinson JK, Ross M, et al. eds. Cancer of the Skin. 2nd ed. Philadelphia, Pa: Elsevier Saunders; 2011:chap 33

11. Wikipedia | Xeroderma Pigmentosum