Busy Lifestyle Syndrome (BLS)

This is a real disorder which causes forgetfulness and lack of concentration in people who take in too much information daily.
A good example of Busy Life Syndrome happens when you can't remember why you just walked into the kitchen or room.

Busy Life Syndrome (Picture Credit; TheMomInMemd )

The syndrome was Coined by Scottish researchers to describe this type of memory loss.
It is commonly seen among women; Hard working mums, wives, nurses etc. Can also be seen in Men. Initially it was common among the adults, but now seen in the young.

Causes
According to a Glasgow-based clinical trials company, the syndrome is caused by hectic lives bombarded with information overload from Mobile  Phones, TV, radio, internet, schools, work etc.
The more things we do and see, the more likely we are to forget things.

Another major cause of Busy Life Syndrome is Sleep deprivation; sleeping less than 6hours at night.

Your brain knows you’re unlikely to need to remember a menial task such as going upstairs to get a book in a few hours, so it erases the memory to make room for more important stuffs which you do everyday. Thus sometimes you can't remember why you walked into the room.

Pathophysiology

When you limit the rest time you force the brain to produce excitatory neurotransmitters such as norepinephrine (which is related to the autonomous system to keep you alive), glutamate (which is involved in memory processes, which produces pleasure), dopamine and acetylcholine vitalize handles muscles.
Your body experiences a sense of pleasure that limits us and keeps us stressed, i.e., a situation that is addictive it involves memory loss and lack of concentration.

Signs and Symptoms
Forgetfulness and lack of concentration.

It should be noted that "forgetting" is part of how a healthy brain works. So it should be little surprise that useful things sometimes get deleted among the constant memory-dumping that our brains do as everyday housekeeping.

If your brain did not forget things, you would continually be recalling all kinds of useless information. It would bury you in mental clutter.
Forgetfulness in Busy Life Syndrome should be differentiated from that seen in early onset of Dementia.

The following examples can be seen in Busy Life syndrome
    Forgetting what you went upstairs for.
    Taking several minutes to recall where the car is parked.
    Forgetting to call a friend back while working from home with misbehaving children.
    Putting things down and being unable to find them soon after.
    Forgetting something trivial a friend mentioned the day before.
    Forgetting the name of someone you’ve just met. 
    Briefly forgetting the word for something — the ‘thingamabob’ moment.

The examples below can be seen in early onset of dementia and they are not symptoms of Busy life syndrome.

    Multi-tasking becomes difficult
    Problems negotiating familiar places, such as you regularly can’t find your vehicle in the car park.    
    Forgetting the names of close relatives and friends.
    Problems recognizing faces, colors, shapes and words. 
    Repeating the same question asked half an hour previously.
    Changing personality.
    Finding that you’ve left objects in the wrong place, such as keys left in the lock, and not remembering leaving them there.

Diagnosis
This is purely Clinical using the history. Its symptoms are not are worrisome as those in Early onset of Dementia.

Differential Diagnosis
Alzheimers Disease.

Treatment
Non Medical;Balance activity with Rest, Take breaks, Sleep.
Cut down the less important activities, Prioritize,
Be realistic, Solve one thing at a time.
Perform any recreational activity that demands skills like drawing, singing, dancing etc.
Stay in touch with others.
Cut down on smoking and alcohol intake.
Healthy diet; seafood, fresh nuts, vegetables, fruits etc.
Exercise.

Medical
This is most often not necessary, although some researchers have proposed that the use of low doses of Memantine, a drug for Alzheimers disease, could help But it has not yet been tested.

Restless legs syndrome (RLS) Or Willis-Ekbom disease

This is a Neurological movement disorder characterized by a distressing need or urge to move the legs or arms (akathisia) usually accompanied by an uncomfortable deep-seated sensation in the legs that is brought on by rest; sitting or lying down, relieved by moving or walking, and worse at night or in the evening.
 It may be accompanied by involuntary limb movements while the patient is asleep and can lead to significant physical and emotional disability. Also called Wittmaack-Ekbom syndrome

It was first described by Sir Thomas Willis in 1672 (the founder of clinical neuroscience) who also described of the Circle of Willis.

Restless Leg Syndrome RLS ( Picture Credit; Orthoapnea )

It affect about 2-15% of the world’s population and Caucasians are more prone to this syndrome than African. Can occur at any age and worsens as the patient gets older, Affects women more than men, with a female:male ratio of 2:1.


Mechanism of the disease (Pathophysiology)
Several mechanisms have been implicated;
1) Genetic/run in families; implicated chromosomes are; 12q, 14q, 9p, 20p, 4q, and 17p in autosomal dominant and recessive pattern
2) Low iron levels; as seen in the substantia nigra (brain) of patients with Restless leg syndrome
3) Abnormalities in the central subcortical dopamine pathways


Causes
This depends on the type; Primary or Secondary.

Primary or idiopathic central nervous system (CNS) disorder; which can be familial, following a pattern of autosomal dominant or recessive inheritance with an earlier age of onset (< 45 years) and slower disease progression. Psychiatric factors, stress, and fatigue can worsen symptoms of restless legs syndrome.

Secondary;
Iron deficiency (Particularly); blood ferritin below 50 µg/L (seen in 20% of cases)
peripheral neuropathy
Hypoglycaemia
Parkinson's Disease
Folate or magnesium deficiency
Vitamin B-12 deficiency
Diabetes mellitus
Frequent blood donation        
Rheumatoid arthritis
Uremia
End-stage renal disease (seen 25-50% of patients with End stage renal disease & may improve after kidney transplantation)
Hemodialysis
Pregnancy (seen in 25-40% of pregnant women & usually subsides within a few weeks after delivery).
Drugs; Alcohol, Caffeine, Beta blockers, Diphenhydramine, Lithium, Antidopaminergic medications, Tricyclic antidepressants, Selective serotonin reuptake inhibitors (SSRIs), Serotonin-norepinepherine reuptake inhibitors (SNRIs) etc.
   


Signs and Symptoms

• An urge to move, usually due to uncomfortable sensations that occur primarily in the legs, but occasionally in the arms or elsewhere uncomfortable.The sensations could be described as painful, antsy, electrical, creeping, itching, pins and needles, pulling, crawling, and numbness, internal itch sensation. Some people have little or no sensation, yet still have a strong urge to move. This sensation is relieved (temporary and partially) by movement mostly Walking. It is Worsened by relaxation (Sitting or lying down) and the severity depends on the duration of the rest.Symptoms worsen in the night and in the morning, though some experience it throughout the day and night; Others experience it only in the morning or only at night.

• Sleep disturbance; About 85% of this patients have periodic movements during sleep, usually involving the legs (periodic leg movements of sleep [PLMS]). PLMS are characterized by involuntary, forceful dorsiflexion of the foot lasting 0.5-5 seconds and occurring every 20-40 seconds throughout sleep, resulting in difficulty falling asleep at night.

• Daytime fatigue

Diagnosis
This is mostly from the history.
The International Restless Legs Syndrome Study Group (IRLSSG) updated its diagnostic criteria in 2012. The current IRLSSG criteria are nearly identical to the DSM-5 criteria.
According to the IRLSSG, Restless legs syndrome (RLS) is diagnosed by ascertaining a syndrome that consists of all of the following features:

(1)An urge to move the legs usually but not always accompanied by or felt to be caused by uncomfortable and unpleasant sensations in the legs.

(2)The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.

(3)The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.

(4)The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.

(5)The occurrence of the above features are not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g., myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping).

Specifier for clinical significance of RLS
The symptoms of RLS cause significant distress or impairment in social, occupational, educational, or other important areas of functioning by the impact on sleep, energy/vitality, daily activities, behavior, cognition, or mood.

Specifiers for clinical course of RLSf

(A)Chronic-persistent RLS: symptoms when not treated would occur on average at least twice weekly for the past year.

(B)Intermittent RLS: symptoms when not treated would occur on average <2/week for the past year, with at least five lifetime events.

Note that ;
i) Sometimes the urge to move the legs is present without the uncomfortable sensations and sometimes the arms or other parts of the body are involved in addition to the legs.

ii) For children, the description of these symptoms should be in the child’s own words.

iii) When symptoms are very severe, relief by activity may not be noticeable but must have been previously present.

iv) When symptoms are very severe, the worsening in the evening or night may not be noticeable but must have been previously present.

v) These conditions, often referred to as “Restless Legs Syndrome mimics,” have been commonly confused with Restless Legs Syndrome, particularly in surveys because they produce symptoms that meet or at least come close to meeting criteria 1–4 above. The list here gives some examples that have been noted as particularly significant in epidemiological studies and clinical practice. However, Restless Legs Syndrome may also occur with any of these conditions, requiring a clear delineation of the Restless Legs Syndrome feelings from the other sensations.

vi) The clinical course criteria do not apply for pediatric cases or for some special cases of provoked Restless Legs Syndrome such as pregnancy or drug-induced Restless Legs Syndrome, in which the frequency may be high but limited to the duration of the provocative condition.

Differential Diagnosis
Other conditions that present like Restless Leg syndrome include;
    Akathisia
    Neuropathy
    Nocturnal leg cramps
    Painful legs and moving toes
    Vascular disease
    Radiculopathy

Investigations
A complete iron panel; iron levels, ferritin, transferrin saturation, and total iron binding capacity.
Complete blood count (CBC)
Blood urea nitrogen (BUN)
Also check for the following;
Creatinine
Fasting blood glucose
Magnesium
Thyroid-stimulating hormone (TSH)
Vitamin B-12 & Folate
Needle electromyography (EMG) and nerve conduction studies should be considered if polyneuropathy or radiculopathy is suspected on clinical grounds, even if the results of the neurologic examination are apparently normal.

Treatment
Medical
For primary Restless Leg Syndrome, drug therapy is only for symptomatic relieve; curative treatment is possible only for secondary Restless Leg Syndrome.

A Task Force of the International Restless Legs Syndrome Study Group (IRLSSG) developed evidence-based guidelines for long-term pharmacologic treatment of RLS which are as follow;

· Pregabalin - Effective for up to 1 year in treating RLS (evidence level, A).

· Pramipexole, ropinirole, and rotigotine - Effective for up to 6 months in treating Restless Leg Syndrome (evidence level, A)

· Gabapentin enacarbil (1 year), pramipexole (1 year), ropinirole (1 year), levodopa (2 years), and rotigotine (5 years) - Probably effective in treating Restless Leg Syndrome for durations ranging from 1 to 5 years (evidence level, B)

· Pergolide and cabergoline - Because of associated safety concerns, not to be used in treating Restless Leg Syndrome unless the benefits clearly outweigh the risks

The IRLSSG Task Force recommends either a dopamine-receptor agonist or an alpha2-delta calcium-channel ligand as first-line treatment therapy for RLS in most patients, with the choice of medication depending on symptom severity, cognitive status, history, and comorbid conditions.

All patients with low iron levels (ferritin < 50 ng/mL) should receive supplemental iron therapy. In iron deficiency, 325 mg of ferrous sulfate may be given with 250 mg of vitamin C. Absorption is increased by taking this on an empty stomach and waiting 60 minutes before eating. Parenteral iron may also have a role in the treatment of RLS secondary to iron deficiency anemia.

Children with low serum ferritin (< 50 ng/mL) should be treated with supplemental iron therapy. Dopaminergic therapy was found to be effective in small series in children with RLS.

Non-Medical Therapy; 

• Sleep hygiene measures should be recommended to all patients. Moreover, patients with mild RLS who are sensitive to caffeine, alcohol, nicotine, selective serotonin re-uptake inhibitors [SSRIs], diphenhydramine, or dopamine antagonists should avoid these substances.

• Exercise may be helpful for some patients; however, physical measures are only partially or temporarily helpful and should be avoided before bedtime. Some patients benefit from different physical modalities before bedtime, such as a hot or cold bath, a whirlpool bath, limb massage, or vibratory or electrical stimulation of the feet and toes.

Non-pharmacologic management and sleep hygiene measures are the treatments of choice in children. A regular sleep/wake schedule and the elimination of stimulating activity and caffeine before bedtime are important measures.

Prognosis
Over time, the symptoms worsen in about 2/3rd of this patients, ranging from mild to intolerable. In addition to being experienced in the legs, sensations also may occur in the arms or elsewhere.
By the age of 50 symptoms usually progresses to severe, daily disruption of sleep leading to decreased daytime alertness. RLS has been associated with reduced quality of life in cross-sectional analysis.
Patients with RLS and periodic leg movements of sleep (PLMS) may be at increased risk for hypertension because PLMS is associated with an autonomic surge and an increase in blood pressure.
Patients may also be more prone to headaches (migraine and tension-type). The headaches are probably secondary to disturbances in sleep associated with RLS and PLMS.

Learning and memory difficulties have also been associated with RLS, presumably secondary to disrupted nocturnal sleep.

Restless Leg Syndrome ( Picture Credit; Fooyoh )

REFERENCES

Abetz L, Allen R, Follet A, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. Jun 2004;26(6):925-35.

Berger K, Luedemann J, Trenkwalder C, et al. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. Jan 26 2004;164(2):196-202.

Cesnik E, Casetta I, Turri M, Govoni V, Granieri E, Strambi LF, et al. Transient RLS during pregnancy is a risk factor for the chronic idiopathic form. Neurology. Dec  2010;75(23):2117-20

Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. Nov 2009;266(5):419-31.

Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Högl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. Jul 2013;14(7):675-84

Giannaki CD, Hadjigeorgiou GM, Karatzaferi C, Maridaki MD, Koutedakis Y, Founta P, et al. A single-blind randomized controlled trial to evaluate the effect of 6 months

of progressive aerobic exercise training in patients with uraemic restless legs syndrome. Nephrol Dial Transplant. Aug 2013;

Godau, Jana; Klose, Uwe; Di Santo, Adriana; Schweitzer, Katherine; Berg, Daniela (2008). "Multiregional brain iron deficiency in restless legs syndrome". Movement Disorders 23 (8): 1184–1187.

Hening WA. Restless Legs Syndrome. Curr Treat Options Neurol. Sep 1999;1(4):309-319.

International Restless Legs Study Group. IRLSSG Diagnostic Criteria for RLS (2012). www.irlssg.org. Updated 2013. Accessed April, 2015

Kutner NG, Zhang R, Huang Y, Bliwise DL. Racial differences in restless legs symptoms and serum ferritin in an incident dialysis patient cohort. Int Urol Nephrol. Jan 2012.

"Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome". American family physician 62 (1): 108–14. 2000

Trenkwalder C, Hogl B, Winkelmann J. Recent advances in the diagnosis, genetics and treatment of restless legs syndrome. J Neurol. Apr 2009; 256(4):539-53.

Aerosinusitis or Barosinusitis

This is painful inflammation or edema of the sinuses (especially the frontal sinuses), which may be accompanied by bleeding and preceded by an upper respiratory tract infection or acute exacerbation of allergies. It occurs when flying in an aircraft or during deep sea diving and is due to non-equilibration or pressure differences of the internal (within the sinuses) and  the external atmospheric pressure.
It can also be called Barotrauma or Sinus squeeze

Paranasal Sinusis (Picture Credit ;Central Coast ENT)

It occurs about 3-4 episodes per 100,000 exposures, has no racial or gender predilection & rarely reported in children, as the frontal sinuses are not fully developed.

Risk Factors

• Upper respiratory tract infection
• Allergy
• Ambient pressure changes or rapid altitude changes; High altitude flyers, high-performance aircraft, military pilots, Deep-sea Divers, Sport divers, Caisson or tunnel workers.
• Nasal polyps
• Anatomic abnormalities of the nose
• Smoking; in children and older adults
• Flying in an airplane after diving

Pathophysiology

Normally,for ventilation and mucocilliary clearance to occur, the sinuses drain through a small ostia into the nasal cavity. This leads to an equilibrium in pressure between the sinuses and the external atmosphere. But when this opening/ostia is blocked by mucousal thickening (as seen in allergies, upper respiratory tract infection, nasal polyps etc) there is no free flow of air (or equilibrium) between the sinuses and the nasal cavity. Following a rapid change in altitude (during flight or diving), there may be compression on the fifth cranial nerve, thus resulting in the Severe frontal headache which is experienced during Aerosinusitis.

There are 2 types of acute barotrauma: The Squeeze and The Reverse Squeeze.
Squeeze occurs during descent; when the sinuses contracts producing a negative pressure, air is trapped causing a partial vacuum within the sinus cavities. If the vacuum is great enough, it causes rupture of the blood vessels in the sinus cavities and may tear the membrane lining. The pain involved is usually sharp, piercing, and severe; upon descent the sinuses may fill with fluids/transudates, and there may be nose bleeding.

The Reverse squeeze occurs during ascent, when the sinuses expand and the pressure increases within the sinuses, but the air within the sinuses cannot escape to the nasal cavity because the ostia is blocked. The expanded sinuses compresses on the fifth cranial nerve, producing frontal headache.

This pathophysiology can be explained by Boyle's law, which states that "the volume of a gas is inversely proportional to the pressure on it, when temperature is constant (V = CT/P)".


Grades
Weissman grading of aerosinusitis;
    Grade I; mild transient sinus discomfort without visible features on X-ray.
    Grade II; pain lasting up to 24 hrs, with some mucosal thickening on X-ray, Serosanguinous Rhinorrhea.
    Grade III; Severe pain lasting more than 24 hrs with X-ray film showing severe mucosal thickening or opacification of the affected sinus; subsequent sinusitis may be observed. Epistaxis, Hematoma and mucosal avulsion.

Signs and symptoms
The predominant symptom is sudden & sharp facial pain or headache during ascent or descent
Mild
 mild pain just above the brow, rarely referred to other regions of the head
 rarely or occassionally have nose bleeding (epistaxis)
Severe
Sudden, sharp and severe pain in the face,and refered to other regions of the head (retroorbital, midface etc).
Accompanied by Nose bleeding (Epistaxis)

Diagnosis
This is Clinical; positive history of the risk factors and symptoms following exposure.
Radiological examination is not really necessary for the diagnosis as this can be done from the history and physical examination. However it may be useful for grading of the Barotrauma.

X-Ray shows mucosal thickening.
CT scanning shows the sinuses involved, extent of any hematoma, and mucosal thickening. It can also suggest the predisposing factor.

Differential Diagnosis
Nasal Polyposis
Turbinate Dysfunction
Seasonal or perineal allergic rhinitis
Nasal septal deviation
Concha bullosa

Prevention
Use a nasal decongestant before ascending or descending,
Avoid rapid descent or ascent,
Avoiding airplanes or scuba diving when you have an upper respiratory infection,
Use valsalva maneuvers to help equalize pressure in the sinuses and inner ears,
Chew gum during take off or landing,
Yawn during flight,
Use filtered earplugs,
Be properly trained before diving.
To prevent pulmonary barotrauma, do not hold your breath during ascent (divers).
Don’t smoke before diving.
Don’t stay under the water at greater depths for so long.
Avoid flying or going to a higher altitude within 24 hours after diving.

Treatment
Most often, immediate treatment is not always possible, but ideally the following should be done;
Immediately return to the altitude which the symptom started (this may be difficult if it happens in a commercial flight) apply topical nasal decongestants before ascending/descending slowly.
Treatment should be aimed at; pain control, ventilation and to prevent infection.
Pain control with analgesics. Depending on the severity, nacortics can be prescribed. Avoid NSAIDs as it may worsen the Hematoma
Ventilation can be aided with nasal decongestants; oral or nasal spray,
Prevent secondary infections using broad spectrum antibiotics (e.g cephalosporins) because the accumulated transudates, hematoma and damaged mucosa can serve as a medium for bacterial growth.
Surgery can be done for very severe cases lasting more than 24hrs and when the analgesics fail to relieve pain. The following surgeries can be performed; Septoplasty, turbinectomy,balloon sinuplasty, Endoscopic sinus surgery etc.


Complications
 Long-term or permanent hearing loss,
 Ear infection,
 Perforated eardrum.
 Orbital cellulitis,
 Meningitis,
 Brain abscess,
 Osteomyelitis (Pott's puffy tumour when the frontal bone is affected)
 Cavernous sinus thrombosis.

Paranasal Sinusis (picture Credit; Pediatrics ENT Associates)

Notes
1) American Academy of Otolaryngology—Head and Neck Surgery; Barosinusitis

2) Brubakk, A. O.; T. S. Neuman (2003). Bennett and Elliott's physiology and medicine of diving, 5th Rev ed. United States: Saunders Ltd. p. 800. ISBN 0-7020-2571-2

3) Encyclopedia Britannica; Aerosinusitis

4) Fitzpatrick DT, Franck BA, Mason KT, Shannon SG (1999). "Risk factors for symptomatic otic and sinus barotrauma in a multiplace hyperbaric chamber". Undersea Hyperb Med 26 (4): 243–7. PMID 10642071.

5) Gunn DJ, O'Hagan S. Unilateral optic neuropathy from possible sphenoidal sinus barotrauma after recreational scuba diving: a case report. Undersea Hyperb Med. Jan-Feb 2013;40(1):81-6.

6) Hanna HH, Tarington CT. Otolaryngology in aerospace medicine. In: DeHart RL, ed. Fundamentals of Aerospace Medicine. Philadelphia: Lippincott Williams & Wilkins; 1985:520-530.

7) Kristin Hayes, Preventing Sinus Squeeze, Ent About. Updated October 30, 2014.

8) Medical Dictionary; Segen's Medical Dictionary. © 2012 Farlex,

9) Medscape; Aerosinusitis

10) US Navy Diving Manual, 6th revision. United States: US Naval Sea Systems Command. 2006.

11) Wikipedia; Aerosinusitis

Harlequin ichthyosis or Harlequin baby

A rare autosomal recessive disease of infants in which the baby is encased in a massive, horny shell of dense, plate-like scale (hyperkeratotic ‘cocoon’) with deep cracks (fissures), accompanied by contraction abnormalities of the eyes (ectropion), turning outwards of a lip (eclabium), and flattened ears.
Also known as; Harlequin-type ichthyosis, keratosis diffusa fetalis, Harlequin fetus

It is the most severe form of autosomal recessive congenital ichthyosis where the dermis to be around 10 times thicker than normal.

Harlequin Baby ( Picture credit; Parakovacs )

It was first Described in 1750 by Rev. Oliver Hart, a cleric from South Carolina. The term "harlequin" derives from the newborn's facial expression, the triangular and diamond-shaped pattern of hyperkeratosis.

It has an incidence rate of less than 1/1,000,000. It has no racial predilection and affects male and female equally.

Risk Factors

• Family History of Ichthyosis or other Severe Skin disorders
• Consanguineous Couples; Marrying a blood relation
• Having another child with ichthyosis ( 25% risk of recurrence)

Pathophysiology

In Harlequin ichthyosis there is Mutations of ABCA12; The gene which is responsible for fat(lipids) transport from lamellar granules to the apical surface of granular layer keratinocytes (spaces between the cells in the skin’s uppermost layer). Thus this mechanism becomes defective resulting in a severe dyskeratosis, caused by defective lipid metabolism; as the lipids are not transported, the stratum corneum is up to 30-fold thicker than the stratum malpighii & the stratum granulosa is decreased to a one-cell layer or absent.

Signs & Symptoms
History of previous intrauterine or neonatal death,
Decreased fetal movements or intrauterine growth retardation noted during the pregnancy,
Preterm delivery,
Bleeding at birth,
Severely thickened & hyperkeratotic skin which is scale-like and shiny with deep cracks/fissures.
Everted eyelids (Ectropion) with dryness of the cornea
The Nose and Ears may be poorly formed or absent
The Lips are retracted (Eclabium)
Sparse hair distribution, alopecias
Poor movement in the joints & contractures
Failure to thrive
Dehydration as a result of fluid loss from the cracked skin.
Hyperthermia due to thickened skin and absence of sweating
Respiratory distress and respiratory failure following poor chest wall expansion

Diagnosis
This is purely clinical, the risk factors, signs and symptoms should be noted.
Prenatal diagnosis, using amniotic fluid sample at 17weeks of gestation, especially for fetuses with positive family history
Prenatal 2D or 3D ultrasonography shows; a large and gaping mouth, aplasia of the nose, abnormal limbs, and bulging eyes; all features of Harlequin ichthyosis.
Genetic testing for mutations in the ABCA12 gene
Full Blood Count; may show decreased heamoglobin, increase White blood cells
Blood culture for infections
Serum Electrolytes Urea and Creatinine may be abnormal due to dehydration.
Chest X-Ray in respiratory distress.
Skin Biopsy for histological studies.

Differential Diagnosis

Self-healing lamellar ichthyosis of the newborn.
Congenital ichthyosiform erythroderma.
Collodion baby.
Lethal restrictive dermopathy.
Infantile systemic hyalinosis.
Neu-Laxova syndrome.

Treatment
The management of Harlequin Ichthyosis is multidisciplinary as well as supportive. It involves the; Neonatologist, Ophthalmologist, Dermatologist, Dietician, Plastic Surgeon, Psychologists etc.
Intravenous access may be difficult here, thus umbilical cannulation is recommended.
Supportive measures include; 

• Monitoring the patient in a Neonatal Intensive care unit,
• The use of Humidified incubator (to maintain body temperature and to prevent the skin from cracking).
• Rehydration
• Lubricating the Cornea with Ophthalmic lubricants
• Emollients can be applied liberally to the skin
• Antibiotics to help prevent infection & sepsis
• Retinoids; Oral(Isotretinoin or acitretin) and Topical Retinoids (Tazarotene) to accelerate shedding of the skin scales.

Complications
Impaired vision
Delayed developmental milestones
Fulminant Sepsis
Failure to thrive
Respiratory failure
Renal failure

Prognosis
The mortality rate for harlequin ichthyosis is high, close to 50%. However, following the discovery of Isotretinoids the prognosis is improving.
Presently, the Oldest surviving person with Harlequin ichthyosis is Nusrit "Nelly" Shaheen, 30years old, from West Midlands in Britain. She was born in 1984,

Harlequin Ichthyosis (Picture Credit; ObGyn)

NOTES

1) Akiyama M. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. Hum Mutat. Oct 2010;31(10):1090-6.

2) Chua CN, Ainsworth J. Ocular management of harlequin syndrome. Arch Ophthalmol. Mar 2001;119(3):454-5

3) First foundation for Ichthyosis and related skin types | Harlequin Ichthyosis

4) Ichthyosis Support Group | harlequin-ichthyosis

5) Kelsell DP, Norgett EE, Unsworth H, et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet. May 2005;76(5):794-803

6) Koochek A, Choate KA, Milstone LM. Harlequin Ichthyosis: Neonatal Management and Identification of a New ABCA12 Mutation. Pediatr Dermatol. Mar 2014;31(2):e63-4.

7) Lefevre C, Audebert S, Jobard F, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet. Sep 15 2003;12(18):2369-78.

8) Medscape; Harlequin Ichthyosis

9) Liu RH, Becker B, Gunkel J, Teng J. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol. Jun 2010;9(6):713-6.

10) Orphanet; ORPHA457, Harlequin ichthyosis

11) Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol. Jun 2011;147(6):681-6.

12) Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0

13) Wikipedia; Harlequin Ichthyosis

Maggot Therapy

Also called; Biodebridement, Maggot debridement therapy (MDT) or Larval therapy.

This is the controlled, therapeutic application of live blowfly (Lucilia sp) larvae ("maggots") into non-healing wounds to to aid in wound debridement (cleaning), disinfection and/or healing.It can also be termed "Therapeutic Myiasis" as we recall that maggot infestation on a living vertebrate host is called "myiasis".

Maggot Therapy (Picture Credit; Science Open)

"Despite our low cultural esteem for maggots, more and more clinicians and patients are turning to medicinal maggots for assistance with their wound healing. For most, the drawbacks of maggot therapy pale in comparison to the remarkable efficacy in treating even the most recalcitrant wounds"- Ronald A. Sherman,

Though It sounds medieval, Maggot therapy is an accepted part of modern medicine as Debridement is an essential component of wound care; the presence of devitalized tissue can impede the healing process.

History Of Maggot Therapy
The beneficial effects of therapeutic myiasis were first observed during the Napoleonic war by Larrey, who noted that soldiers whose wounds had become infested with maggots had an improved prognosis.
William Baer, while at Johns Hopkins University in Baltimore, Maryland, may have been the first person to have intentionally applied larvae to wounds in order to induce wound healing. During the late 1920's, he identified certain species, raised them in the laboratory, and used their larvae to treat several children with osteomyelitis and soft tissue infections. He presented his findings at a surgical conference in 1929. Two years later, after treating 98 children, his findings were published posthumously.
Throughout the 1930’s Maggot Therapy was performed routinely by Doctors until the discovery of new antibiotics and surgical techniques that came out during World War II. Maggot therapy was occasionally used during the 1970's and 1980's, but only when antibiotics, surgery, and modern wound care failed to control the advancing wound.

The emergence of antibiotic-resistant strains of bacteria such as methicillin resistant Staphylococcus aureus (MRSA) and the curiosity of researchers prompted the reemergence of larval therapy during 1970's & 1980's . As a treatment it meets the demands of clinical governance, being not only beneficial to the patient, but also being proven to be more cost-effective.

In January 2004, the U.S. Food and Drug Administration (FDA) granted permission to produce and market Medicinal maggots. Same year the British National Health Service (NHS) gave approval for maggot therapy. Presently, about 30 countries around the world are using Maggot therapy; In Africa, it is being used in Kenya & South Africa. In European Union, Canada, Japan, maggots are classified as medicinal drugs, needing a full market license.

Mechanism Of Action
Debridement; The maggots secrete a broad spectrum of digestive juice (collagenases, proteolytic enzymes, serine proteases) that selectively liquefy and absorb only necrotic tissue (extracorporeal digestion). Also Mechanical Debridement by the specific mandibles or “mouth hooks” of the maggots and their rough body which both scratch the necrotic tissue.

Disinfection; It was discovered that secretions from maggots (allantoin, urea, phenylacetic acid, phenylacetaldehyde, calcium carbonate, proteolytic enzymes, etc) have broad-spectrum antimicrobial activity, and microbes not killed by these secretions are subsequently ingested and lysed within the maggots. Maggot secretions have been found to dissolve biofilms.

Stimulation of healing; The alkalinity of maggot-treated wounds, along with the isolated allantoin and urea-containing compounds is responsible for wound healing. In fact, today, allantoin and urea are components of many cosmetics. Maggot secretions also;
 -stimulates the proliferation of fibroblasts and endothelial tissue ,
 -increases angiogenesis,
 -enhances fibroblast migration over model wound surfaces.
Using remittance spectroscopy to evaluate patients before and after maggot therapy, Wollina and colleagues found that vascular perfusion and tissue oxygenation surrounding the wound actually increased following maggot therapy. Zhang and colleagues are currently seeing evidence that maggot extracts may even stimulate the growth of neural tissue.

Uses/Indication

• Diabetic Foot Ulcer
• For debriding non-healing necrotic skin and soft tissue wounds including;

               -pressure ulcers,
               -venous stasis ulcers,
               -neuropathic foot ulcers,
               -non-healing traumatic or post-surgical wounds
               -infectious

• In diabetic and non-diabetic subjects for wound bed preparation prior to surgical closure.

Dosage & Administration
Maggots are applied to the wound at a dose of 5–10 larvae per square centimeter of wound surface area and are left within their dressing for 48–72 hrs. At that point they are satiated (as evidenced by increase in size), finished working, and can be removed and safely disposed.

Maggot therapy being a controlled therapeutic myiasis (maggot infestation on a live host) is controlled by;

selecting a safe and effective species and strain,

• chemical disinfection to make the maggots germ-free (sterile maggots),
• containing the maggots within special dressings(e.g maggot confinement dressings; Le Flap™,Biobag™ ) that prevent them from leaving the wound unescorted,
• quality control measures throughout the breeding and production processes.

Not all species are safe and effective. The maggots cleared for marketing in the United States belong to the (currently named) LB-01 strain of Phaenicia (Lucilia) sericata.

Advantages Of Maggot Therapy

1. Takes about 15-30 minutes to apply a secure dressing to keep the maggots in place
2. Low cost of treatment
3. Excellent safety record.
4. Simple enough that non-surgeons can use it to provide thorough debridement when surgery is not available or is not the optimal choice
5. Provide surgical quality debridement as an outpatient or in the home
6. Provides treatment for wounds infected by strains of methicillin resistant Staphylococcus aureus (MRSA)
7. As larvae are typically applied for 3 days, wounds are disturbed less frequently than conventional dressings that require changing everyday

Disadvantages

1. Bacteria like Pseudomonas aeruginosa, Escherichia coli, Enterococcus, Proteus are not attacked by maggots and in case of Pseudomonas even the maggots are in danger. Consequently, using maggots alone might lead to a change of bacteria cultures on the wound.
2. Ineffective in case of highly discharging or dried wounds
3. Medicinal maggots are highly perishable and susceptible to transportation problems and delays. Young, starving larvae require food, water, and oxygen, and they are temperature sensitive. Therefore they must be shipped by overnight courier, and their arrival should be timed no more than 24 h before their application to the wound. Delivery delays and exposure to extreme temperatures decrease their survival.
4. Occasionally the maggots may escape from the wounds and 1–2 weeks later become adult flies (“used maggots” and flies are essentially mobile fomites)
5. Local discomfort, itching, unaesthetic appearance to the patient along with cost of the therapy and short half life of maggots
6. It cannot be used in open wounds of body cavities as the environment is not suitable
7. Negative perception with which it is regarded by both patients and doctors; The 'yuk factor'

Side Effects
Minor bleeding,Pain,
Excessively induced exudates,
Increased body temperature,
Flu-like symptoms,
Allergic reaction,
Skin maceration
Discomfort.

Contraindications
Patients refusal.

Alternative Therapies

• Biotherapies like; apitherapy (application of honey) and application of leeches.
• Sonotherapy (with use of ultrasounds)
• Hydrosurgical therapy (with use of water jets)
• Hyperbaric Oxygen Therapy (HBOT)

Medical Maggots™ (Picture Credit; Live science)

Maggot Debridement Therapy (Picture Credit; btmcl)

NOTES
1) A. J. Horobin, K. M. Shakesheff, S. Woodrow, C. Robinson, and D. I. Pritchard, “Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon interactions between human dermal fibroblasts and extracellular matrix components,” The British Journal of Dermatology, vol. 148, no. 5, pp. 422–933, 2003.

2) A. G. Smith, R. A. Powis, D. I. Pritchard, and S. T. Britland, “Greenbottle (Lucilia sericata) larval secretions delivered from a prototype hydrogel wound dressing accelerate the closure of model wounds,” Biotechnology Progress, vol. 22, no. 6, pp. 1690–1696, 2006.

3) Dariusz Waniczek, Andrzej Kozowicz, Małgorzata Muc-Wierzgoń, Teresa Kokot, Elżbieta Świętochowska, and Ewa Nowakowska-Zajdel, "Adjunct Methods of the Standard Diabetic Foot Ulceration Therapy,"  Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 243568 Chapter 3

4) P. E. Prete, “Growth effects of Phaenicia sericata larval extracts on fibroblasts: mechanism for wound healing by maggot therapy,” Life Sciences, vol. 60, no. 8, pp. 505–510, 1997.

5) R. A. Sherman, "Mechanisms of Maggot-Induced Wound Healing: What Do We Know, and Where Do We Go from Here?" Evidence-Based Complementary and Alternative Medicine
Volume 2014 (2014), Article ID 592419

6) R. A. Sherman, “Maggot therapy for foot and leg wounds,” International Journal of Lower Extremity Wounds, vol. 1, no. 2, pp. 135–142, 2002.

7) R. A. Sherman, "Maggot Therapy takes us back to the future of wound care: New and Improved Maggot Therapy for 21st Century" J Diabetes Sci Technol. 2009 Mar; 3(2): 336–344.

8) U. Wollina, K. Liebold, W. Schmidt, M. Hartmann, and D. Fassler, “Biosurgery supports granulation and debridement in chronic wounds—clinical data and remittance spectroscopy measurement,” International Journal of Dermatology, vol. 41, no. 10, pp. 635–639, 2002.

9) Wikipedia, "Maggot Therapy"

10) W. Robinson, “Stimulation of healing in non-healing wounds by allantoin occurring in maggot secretions and of wide biological distribution,” Journal of Bone and Joint Surgery, vol. 17, pp. 267–271, 1935

11) Z. Zhang, S. Wang, Y. Diao, J. Zhang, and D. Lv, “Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity,” Lipids in Health and Disease, vol. 9, article 24, 2010.

12) Z. Zhang, S. Wang, X. Tian, Z. Zhao, J. Zhang, and D. Lv, “A new effective scaffold to facilitate peripheral nerve regeneration: chitosan tube coated with maggot homogenate product,” Medical Hypotheses, vol. 74, no. 1, pp. 12–14, 2010.

Myiasis

 Infestation of a live Vertebrate (human or animal)  by the larvae of flies, characterized as cutaneous (subdermal tissue), gastrointestinal, nasopharyngeal, ocular or urinary symptoms depending on the region invaded. Often caused by two-winged (dipterous) flies.

Oral Myiasis

This condition was first observed by Ambroise Paré, the chief surgeon to King Charles IX and King Henry III, who said that maggots often infested open wounds, but the term "Myiasis" was coined by Reverend Frederick William Hope in 1840 to refer to diseases resulting from dipterous larvae which differs from those caused by other insect larvae(scholechiasis).

The name Myiasis comes from the Greek word "myia" which means "fly"

Epidemiological data on human myiasis are scant as registration of cases is not usually obligatory
Myiasis is not prevalent in any particular race & has no sex or age predilection.

Risk Factors.
The following risk factors for developing myiasis;
Traveling to endemic areas.
Tropical and subtropical countries (climatic conditions)
Children are particularly prone to the infestation ( thinner skin and lesser immunity),
elderly, psychiatric patients, alcoholics, and other helpless patients,
homeless,
Poor hygiene,
Poor socioeconomic circumstances,
presence of an open wound (preexisting suppurative lesions)
population Hits, (e.g sitting or lying on the ground and some religious rites).
Dermatologic Conditions (e.g Neuropathic ulcers,cutaneous B lymphoma, leprosy etc.)

Pathophysiology

Dermatobia hominis/human bot fly (South and Central America);  the female egg-bearing Bot fly catches a blood-sucking arthropod (e.g a mosquito), and attaches her eggs to its abdomen (means of transportation known as phoresy). When the mosquito takes a blood meal from human, the local heat induces the eggs to hatch and drop to the skin of the host and enter painlessly through the bite of the carrier or some other small trauma.This gives rise to  Furuncular myiasis.

Cordylobia anthropophaga/tumbu fly (Sub-Saharan Africa); The Tumbu fly is attracted by the odor of urine and feces. The females lay their eggs on dry, sandy soil or on damp clothing hung out to dry. The eggs hatch in 1-3 days and can survive near the soil surface or on clothes for up to 15 days waiting for contact with a suitable host. Activated by heat, such as the body heat of the potential host, they are capable of penetrating the unbroken skin with sharp mandibles resulting in  Furuncular myiasis.

Cochliomyia hominivorax/blow fly (South and Central America) The adult Female Blow flies deposit the eggs near poorly managed wounds and the larvae feed on necrotic tissue resulting in Wound Myiasis. Flies may be dispersed by prevailing winds, and infection is often acquired while resting outside during the day or may result from trauma.

Cuterebra sp (North America)
Wohlfahrtia sp (Europe, North America, and Pakistan)

Signs & Symptoms

• History of an insect bite which precedes the lesion
• In human beings, the most common site is the eye
• severe eye irritation, pain, redness,swelling of the eyelids, foreign body sensation & lacrimation are common symptoms of patients with ophthalmomyiasis.
• epistaxis, foul smell, passage of worms, facial pain, nasal obstruction, nasal discharge, headache, dysphagia, and sensation of foreign body in the nose can be seen in Nasal Myiasis.
• Myiasis is very painful, with sudden paroxysmal episodes of lancinating pain
• intense itching (Pruritus)
• at first, It looks like an ordinary large boil,often ooze (serosanguineous drainage or purulent fluid),
• a small aperture is seen covered by a crust at the apex ( central punctum ), on removal of this crust, the posterior end of the larva can be seen.
• Crawling sensation,
• Fever.

If the condition is left to itself, in due course the larva dilates the opening by means of its posterior end and eventually escapes, and crawls away and becomes a pupa.

Classification of Myiasis
a)Ecological Classification of myiasis;

• 1)Specific/obligatory Parasite dependent on host for part of its life cycle
• 2)Semispecific/facultative ;  Primary; The fly-larva is the true cause of the condition (Free living and initiates myiasis). Secondary; The fly-larvais a secondary invader (Free living and unable to initiate myiasis).  Tertiary; Free living and unable to initiate myiasis; may be involved when host is near death.
• 3)Accidental/pseudomyiasis;  Free-living larva & not able to complete its life cycle; causes pathological reaction when accidentally in contact with the host

b)Anatomical classification of myiasis
Classification by Zumpt      Classification by Bishopp               Classification by James
Sanguinivorous                     Bloodsucking                                  Bloodsucking

Dermal/subdermal                Tissue-destroying                            Furuncular
                                              Subdermal migratory                      Creeping
                                                                                                      Traumatic/wound
                                                                                                      Anal/vaginal

Nasopharyngeal                  Infestation of the head passages        Nose, mouth, sinuses
                                                                                                       Aural
                                                                                                       Ocular

Intestinal                             Intestinal/urogenital                           Enteric
                                                                                                       Anal/vaginal

Urogenital                          Intestinal/urogenital                            Bladder, urinary passages
                                                                                                       Anal/vaginal


Diagnosis
This is solely clinical;
Patients gives history of traveling to an endemic area or insect bite.
elevated immunoglobulin E, marked Eosinophilia and leukocytosis can be seen on Laboratory investigation
Dermoscopy; identifies the posterior parts of the maggot within a lesion. The examination reveals a central opening surrounded by dilated blood vessels and a yellowish structure with black barblike spines in Furuncular Myiasis.
Rhinoscopy Can be used to diagnose Nasal Myiasis.
Ultrasound confirms cases of furuncular myiasis and helps in the complete removal of the larva. A definitive diagnosis of myiasis can be achieved if larval movement is detected during the ultrasound. Color Doppler sonography has proven to be useful for the detection of the larvae when ultrasound is not able to detect it.


Differential Diagnosis
Furunculosis, Insect bite, Abscess,Cellulitis, Pyoderma, Inflamed cyst, Tungiasis, Delusional Parasitosis,
Labial cases may be confused with labial cellulitis.
Breast myiasis may be confused with periductal mastitis, benign mass with microcalcification, and inflammatory carcinoma.
Clinical and radiologic confusion with arteriovenous (AV) malformation and hemangioma occurred in one case of preauricular myiasis.
herpes simplex, helminthic cutaneous larva migrans, gnathostomiasis, sparganosis.
Hypereosinophilic syndrome,
Exaggerated arthropod reaction,
Foreign body reaction,
Lymphadenopathy,
Onchocerciasis (River Blindness)

Treatment
The following methods can be used in the treatment of Myiasis;
1)Occlusion/suffocation approaches- This method prevents the larva from having access to atmospheric Oxygen, thus forcing it to migrate to the surface. To achieve this, place petroleum jelly, liquid paraffin, beeswax, heavy oil, or bacon strips over the central punctum.

2)Systemic/topical ivermectin; An alternative treatment for all types of myiasis is oral ivermectin or topical ivermectin (1% solution), proven especially helpful with oral and orbital myiasis.

3)Surgical removal with local anesthesia; This is an invassive proceedure, anasthetize locally  with lidocaine. After removal of the larvae, antiseptic dressings, thorough cleansing, and debridement are indicated.

4)Wound Debridement for Wound myiasis; irrigate wound to eliminate the larvae from the wound or surgical removal. Application of chloroform, chloroform in light vegetable oil, or ether, with removal of the larvae under local anesthesia, has been advocated for wound myiasis.

Complications
Secondary bacterial Infection
Cellulities
Local enlarged lymph nodes (lymphoadenopathy)
fistula formation.
Cerebral infestation
Death

Oral Myiasis (Picture Credit; Reddit)

NOTES
1) Aydin E, Uysal S, Akkuzu B, et al. Nasal myiasis by fruit fly larvae: a case report. Eur Arch Otorhinolaryngol. Dec 2006;263(12):1142-3.

2) Dorland's Medical Dictionary for Health Consumers. © 2007 by Saunders, an imprint of Elsevier, Inc

3) Fabio Francesconia and Omar Lupi. Myiasis Clin Microbiol Rev. 2012 Jan; 25(1): 79–105. 

4) Hope FW. 1840. On insects and their larvae occasionally found in the human body. Trans. R. Entomol. Soc. Lond. 1840: 256–271

5) James MT. 1947. The flies that cause myiasis in man, p 1–175 U.S. Department of Agriculture miscellaneous publication no. 631. USDA, Washington, DC

6) James, WD, Berger, TG, Elston, DM. Myiasis. In: Andrews' Diseases of the Skin. 11th ed. Elsevier; 2011:438

7) Masoodi M, Hosseini K. External ophthalmomyiasis caused by sheepbotfly (Oestrus Ovis) larva: a report of 8 cases. Arch Iran Med. 2004;7:136-139.

8) Sharma H, Dayal D, Agrawal SP. Nasal myiasis: review of 10 years experience. J Laryngol Otol. May 1989;103(5):489-91.

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.