Types

Types on Congenital Pain Indifference (CIP)

Insensitivity to Pain means that the painful stimulus is not even perceived i.e. a patient cannot describe the intensity or the type of pain.

Indifference to Pain means that the patient can perceive the stimulus but lacks appropriate responses i.e. they will not flinch or withdraw when expose to pain.

Symptoms

Symptoms

For patents with this autosomal recessive disorder ‘Congenital Insensitivity to Pain (CIP)’ ‘Cognition’ and ‘Sensation’ are otherwise normal for example the patient can still feel discriminative touch (though not always temperature) and there is no detectable physical abnormalities.

Children with this condition often suffer oral cavity damage both in and around the oral cavity (such as having bitten of the tip of their tongue) or fractures to bones. Unnoticed infection and ‘corneal damage’ due to foreign objects in the eye are also found. Because the child can not feel pain they may not respond to problems, thus being at a higher risk of more severe disease or otherwise.

In some patients a mild intellectual disability as well as an impaired corneal reflect also noticed. 

Difference between CIP & CIPA

Difference between Congenital Insensitivity to Pain (CIP) & Congenital Insensitivity to pain with Anhidrosis (CIPA)

The difference between CIP & CIPA is that in CIP the person only cant feel pain but in case of CIPA the person cannot sweat and probably has malformations in his/ her body.

CIP

What is Congenital Insensitivity to Pain (CIP)?

Congenital Insensitivity to Pain (CIP) also called Hereditary Sensory Automatic Neuropathy (HSAN) is a disease that affects the centry nerves that is caused by a genetic mutation that prevents the formation of nerve cells called nociceptors or axonicas endings also called pain nerves, that are specialized pain receptors to feel pressure, temperatures and stretching in and around their tissues. 

There is a similar kind of disease called Congenital Insensitivity to pain with Anhidrosis (CIPA) in which the nervous system prevents the sensation of pain, heat, cold or any real sensation with inability to sweat normally.

Historical Background

Reports of individual who appeared insensitive to pain from birth onwards have a long history but it was not until the 1930’s that this condition attracted medical attention.

The 1^st case was reported by Dr. Dearborn in 1932 — he described his patient who acts as a human pincushion in a circus and crucifixion had to be called off when a woman in the audience fainted after a spike was driven through his one hand.

Initially, various terms were used to describe these individuals including ‘Congenital General Pure Analgesia’ (Dearborn, 1932), ‘Congenital Universal Insensitiveness to Pain’ (Ford & Wilkinsons, 1938), ‘Congenital Universal Indifference to Pain’ (Winkelmann et al., 1962). As these labels show, the phenomenon encompasses diverse abnormal responses to pain. Some patients have an absence of responses to injury, abnormal automatic responses to painful stimuli and difficulties in distinguishing various types of stimuli, whereas others exhibit lack of responsiveness to the stimuli but retain the ability to identify stimulus presence and mobility.

Over time 2 terms predominantly describe these individuals — ‘Congenital Insensitivity to Pain’ (McMurray 1950) and ‘Congenital Indifference to Pain’ (Jewesbury, 1970). Although the terms were often used interchangeably, only in recent years they have acquired distinct meanings and careful authors now to use them to distinguish two groups of individuals (Jewesbury, 1970; Landrieu et al., 1990).

Patients with congenital insensitivity pain seem not to perceive sensations of pain i.e. they have remarkably impaired ability to perceive the type, intensity and quality of painful stimuli. On the other hand, those with congenital indifference to pain, however, painful stimuli are perceived but there is an absence of the affective response to pain, rather than a lack of signal transmission. These individual reports experiencing sensations of pain but exhibit no aversion to or withdrawal from painful stimuli.

LIFE WITHOUT PAIN !!!!!

How would life if there is no pain? Don’t we thing a life without pain sounds great.

THINK AGAIN!!!

What happens if we do not feel pain?

WE SIMPLY CAN’T LIVE!!!

NO PAIN NO GAIN. Yes that’s true for our daily life also.

PAIN warns us that something is not right. Pain is body’s way of warning from impending injury and important defence mechanism in day to day life.

PAIN teaches children not to put their hands on hot plate because they know that heat hurts. It urges us to consult doctor when pain persists in any part of our body.

On the contrary what about pain that accompanies something which has already been diagnosed? What about the persistent pain that frequently escorts chronic conditions such as a sore back or cancer? Who can see the good/positivity in that kind of pain?

Though there may be instances when it seems superfluous and even cruel, the sensation of pain is more necessary that is not.

It is a clear indication that there is something wrong and that it needs to be seen to. In the absence of pain, no alert signals are given off—which could ultimately put our life in danger.

The sensation of pain is a complex sensation with many a meaning and many a pathway. One particular pathway was discovered when members of a family were incapable of feeling pain—a singular and rare condition due to the loss of functions of a protein known as ‘SCN9A’ or Na_v1.7

The loss of function of SCN9A/Na_v1.7 protein leads to a rare autosomal disease/disorder —‘Congenital Insensitivity to Pain’ — belongs to the family of Hereditary Sensory and Autonomic Neuropathies (HSAN).

Consultation

Consultation with the following specialists may be helpful:

ü  Neonatologist

ü  Dermatologist

ü  Medical geneticist

ü  Social worker

Some researcher recommended early formation of a multidisciplinary team

ü  Ophthalmologist

ü  Dietician

ü  Ear-nose-throat specialist

Medical Care

Airway Maintenance

In treating this severe and very rare genetic skin disorder (harlequin ichthyosis) upon delivery, the baby’s airway and circulation is the foremost priority. The healthcare team must ensure that the baby’s/patient's airway, breathing, and circulation are in stable condition after delivery. The baby will require intravenous access. It will be through the access where the medication will be given. Peripheral access may be difficult. Umbilical cannulation may be necessary. The infant must be placed in a humidified incubator, the temperature, respiratory rate, heart rate and oxygen saturation must be monitored by the healthcare team. Once the vital sign have stabilized the baby is then transferred into a level 3 neonatal nursery station or room.

Projection of Conjunctiva

Expose keratitis results from ectropian of the eye-side. It is necessary to apply ophthalmic lubricants frequently to protect the conjunctivae. It is advisable to bathe the infants twice daily and use frequent wet sodium chloride compresses followed by application of bland lubricants to soften hard skin. Topical keratolytics (eg, salicylic acid) are not recommended in newborns because of potential systemic toxicity.

Intravenous Access for Feeding

It is prescribed to have intravenous access for intravenous fluids as it is almost always required. Neonates with harlequin ichthyosis initially do not feed well. There is a need to calculate daily fluid requirements since the neonates will experience excess cutaneous water losses. In addition to that, monitoring of serum electrolyte levels is required. There also having a high risk of hypernatremic dehydration.

Sterile Environment

The sterile environment has to be always maintained to avoid infection. Frequent cultures of the skin should be taken. Growth of pathogenic organisms (eg, Staphylococcus aureus, Pseudomonas aeruginosa) indicates risk of sepsis. The blood culture has to be drawn as sepsis can occur quickly in affected infants. A consensus does not exist regarding the use of prophylactic antibiotics in these patients.

Laboratory Studies

Genetic testing for mutations in the ABCA12 gene is available. Complete sequence analysis of the coding region of this gene is performed to identify specific mutations. Peripheral blood cells or cells from buccal smear from affected individuals are required. Carrier testing is available for a relative after the proband’s mutation is identified. Prenatal diagnosis is available for fetuses with suspected harlequin ichthyosis, which may or may not have a family history of the disorder.

The following laboratory investigations may be helpful for newborn to identify complications of harlequin ichthyosis.

ü  Check the WBC count and blood cultures for signs of infection.

ü  Closely monitor serum electrolyte levels, which may be abnormal secondary to dehydration.

ü  Check BUN and creatinine levels for signs of renal failure.

ü  Monitor hemoglobin levels because anemia is reported.

Prenatal 3-Dimensional (3D) ultrasonography may show features suggestive of harlequin ichthyosis.

Chest Radiography may be indicated if respiratory distress is present postnatally.

Renal Ultrasonography may be indicated if renal failure or poor urine output is evident or if findings from the physical examination are abnormal. Renal dysplasia is indicative to harlequin ichthyosis.

Skin Biopsy at any cutaneous site (including the palms and the soles, excluding mucous membranes) may be done to acess the histopathologic characteristics and ultrastructural features.

Histologic Findings

The stratum corneum is thick and compact. Hyperkeratosis may be more marked around hair follicles compared with the interfollicular epidermis. Parakeratosis and orthokeratosis may be present, particularly on the fingers and the toes. Cells within the stratum corneum are abnormally keratinized. Granular, spinous basal cell layers appear unremarkable. Inflammatory cells may infiltrate the papillary dermis.

Electron Microscopy reveals absent or abnormal lamellar granules within the granular layer keratinocytes. Lamellae are absent in the intercellular spaces between the granular cell layer and the cornified cell layer. Densely packed lipid droplets and vacuoles are seen within the cytoplasm of the aberrantly cornified cells of the stratum corneum. These lipid inclusions involve the entire skin surface but are more evident on the palms and the soles. Keratohyalin granules may be absent, normal, or abnormally small and globular. Keratin intermediate filaments within granular cells may have reduced density.

ü  Amniotic fluid can be tested for over production of ‘Keratin’ in 17^th weeks of pregnancy to disgnosize this disease in early stage.

ü  Foetal skin biopsy can be done at 20^th week of pregnancy for early detection of harlequin ichthyosis.