Diagnosis

Diagnosis is based upon symptoms, signs and investigations. Normal diameter of portal vein is 11 mms. Ultrasound may report diameter larger than this. Actual measurement of pressure or venography is not needed as symptoms and signs are sufficient to make this diagnosis.

Management

Simple dietary measurements like salt restriction.
Addition of spironolactone
Later on loop diuretics like frusamide
Beta-Blockers for prophylaxis against bleeding.

Propranolol and Nadolol (Corgard) have been studied for this purpose. These are helpful. Nadolol is prefered as it is more selective. Blood pressure and pulse rate shall be monitored. Pulse rate shall not drop to less than 75 % of pretreatment figure. These agents can be started even when there is no history of bleeding but diagnosis is fairly established.

Ascites. Main Causes

Cirrhosis of Liver

Tuberculosis
Malignancy
Systemic diseases like Nephrotic Syndrome and CCF

A small amount of fluid should be always aspirated and sent for laboratory examination to establish diagnosis.This is essential step for Tuberculosis and malignancy.

Pathophysiological factors.

Low serum albumin
Portal hypertension

Salt retension due to distrubed metabolism of aldosterone and related hormones.
Disturbed lymphatic flow.

Management Stepwise approach shall be used to manage patients on long term basis.

Salt restriction.
Spironolactone upto 100-300 mgs daily
Addition of loop diuretics likes frusamide.

These measures may fail and ascites may be producing symptoms like respiratory distress. Such refractory ascities can be managed by following measures.

Refractory Ascites.

Rule out infections. Cytological examination of peritoneal fluid should decide this factor. Cell count of 250 in symptomatic patients (low-grade fever, tenderness, and pain) and 500 in asymtomatic patients shall be taken as evidence of infections. Ciproxin and third generation cephalsporins are athe antibiotics of choice.

Paracentesis: Now paracentesis is accepted as therapeutic measure.

Shunt for ascites is simple measure. Tube from peritoneal cavity to jugular vein. This is available easily. But shunts for portal hypertension (ITP) are not easily available.

Albumin: This is only a temporary measure. Half-life of this albumin is only 1-2 weeks.

**************************

Autoimmune Hepatitis.

Clinical Features.

When all features of hepatitis are present in a young female patient, accompanied by disturbed liver profile and negative serology for viruses then this is the diagnosis, which should appear in our list of DD.Pruritis, and severe ache pains, are prominent features. These appear early and are quite severe. This condition is also associated with systemic manifestations.

Investigations. ESR is raised. Biopsy will clinch the diagnosis. Disturbed lipid profile and presence of ANA, ASA, and AMA characterize it.

Prognosis it follows slows downhill course to cirrhosis. Steroids and immunosuppressive therapy can modify the response and may delay the progress.

Immunological symptoms associated with

Chronic viral hepatitis

Are you alive to this scene?

More and more patients with complaints of arthralgias and joint pains after receiving antirheumatic treatment (NSAIDS) for months or even years, end up with the diagnosis of chronic hepatitis. Some patients are diagnosed after the first episode of hematemisis due to NSAIDS.In this background panel was interested to know the views of our expert on this aspect.

In all chronic infections immune system is loaded up with the products of antigen antibody reaction. These products cross react with many tissues, especially basement membrane. Many chemicals are released. Serotonin is one of these. This is especially blamed for fatigue and prurtitis. Manifestations from these secondary effects of all chronic infections such as chronic viral hepatitis are usually systemic, affecting all systems.

Kidney: Membranous glomerulonepheritis ending up in nephrotic syndrome.

Skin: Pruritis, Vasculitis.Porphyria,

Blood Purpura (petechiae), Haemophilic anaemia.

Eye fundal haemorrhages

Musculo-

Skeletal System: Hepatitis B is especially notorius to produce artheritis. Fatigue, Myalgia, arthralgias are frequent complaints. Significane is use of NSAIDS, which are severely contraindicated in chronic viral hepatitis as for effects on liver and stomach are concerned.

Childpugh Classification table to assess hepatic function.

This table is helpful to decide

The grading of compensation as A, B or C.

Criteria A B C

Minimal Moderate Advanced.

< Than 2.0 mgs 2-3 mgs > 3 mgs

Bilirubin.mgs/dl

Albumin gms/dl > 3.5 3-3.5 < 3

Ascites None Easily poorly

Controlled Controlled

Encephalopathy. None minimal Advanced

Coma

Nutrition Excellent Good Poor

Wasting.

End of Panel Interview

Clinical Presentations of Liver Diseases.

Initial Detection

Incidental or Routine findings. Detected while mananging or investigating a problem apparently not related with Liver.

Non specific clinical presentations. Liver should be investigated.

Specific presentations. Here first & principal accused is Liver on the basis of predominant features of clinical presentation.

Incidental Findings

Abnormal ALT.
Virology screening
Ultrasound examination of abdomen for abdominal complaints or in routine screening, e.g for blood donation.
Bleeding disorders
Hepatosplenomegaly
High MCV for Anaemia investigations.

Non Specific Findings

If liver is palpable then decide

If liver is enlarged or displaced.(Upper border)
It is really liver and not any other viscera like

Gall bladder,

Colonic Neoplasm

Kidney

Faecal material in Colon.

Edge is nontender ,tender,

Sharp,rounded,angular,irregular,

Firm or soft,or hard.

Pulsatile

Surface of Liver smooth ,regular irregular or nodular

Few Typical liver Presentations.

Cirrhotic Liver is firm in consistency with irregular or nodular surface Usually it is not palpable.

Slightly enlarged liver,with tender and rounded edge is seen in Acute hepatitis and CCF.Painful enlargement is a feature in Acute inflammations,hepatic abcess,and acute CCF.

Hard like rock palpable liver with irregular or nodular edge is typical of malignancy.
Rapid decrease in size with treatment confirms the diagnosis of CCF.If with deterioating clinical condition size decreases rapidly,it may indicate massive necrosis.Rapid mobilization of fat may also produce rapid decrease in size.

Pulsatile liver is associated with right heart failure(Tricuspid regurgitation).

Investigations of Liver

Let us be sure what are we investigating.

There are innumerable investigations, investigating one aspect of the liver or the other directly or indirectly. Before we order or interpret any investigation, we must be clear in our minds, what we are looking for.

Liver cell damage.
Type of cell damage
Total function of Liver.
Obstruction to biliary flow.

Most Common Misnomer is LFTs Liver function tests

Markers of function = Albumin and bilirubin

Markers of liver damage = Alanine Transaminase, Alkaline phosphatase, and -Glutamyl transferase.

These give useful information about the nature of the liver insult: a predominant rise in alanine transaminase activity (normally contained within the hepatocytes) suggests a hepatic process. Serum transaminase activity is not usually raised in-patients with obstructive jaundice, although in patients with common duct stones and cholangitis a mixed picture of raised biliary and hepatic enzyme activity is often seen. Rarely only AST (SGOT) is raised while ALT (SGPT) is normal in cell damage.

Alkaline Phosphatase

Epithelial cells lining the bile canaliculi produce alkaline phosphatase, and its serum activity is raised in patients with intrahepatic cholestasis, cholangitis, or extrahepatic obstruction; increased activity may also occur in-patients with focal hepatic lesions in the absence of jaundice. In cholangitis with incomplete extrahepatic obstruction, patients may have normal or slightly raised serum bilirubin concentrations and high serum alkaline phosphatase activity. Serum alkaline phosphatase is also produced in bone, and bone disease may complicate the interpretation of abnormal alkaline phosphatase activity. If increased activity is suspected to be from bone, serum concentrations of calcium and phosphorus should be measured together with 5'-nucleotidase or -Glutamyl transferase activity; these two enzymes are also produced by bile ducts, and their activity is raised in cholestasis but remains unchanged in bone disease.

Plasma Proteins.

A low serum albumin concentration suggests chronic liver disease.

Most patients with biliary obstruction or acute hepatitis will have normal serum albumin concentrations as the half-life of albumin in plasma is around 20 days and it takes at least 10 days for the concentration to fall below the normal range despite impaired liver function. The presence of a low serum albumin concentration in a jaundiced patient suggests a chronic disease process.

Serum globulin titres rise in chronic hepatitis and cirrhosis, mainly due to a rise in the IgA and IgG fractions.
High titres of IgM are characteristic of primary biliary cirrhosis.
IgG is a hallmark of chronic active hepatitis.
Ceruloplasmin activity (ferroxidase, a copper transporting Globulin) is reduced in Wilson's disease.
Deficiency of 1 antitrypsin (an enzyme inhibitor) is a cause of cirrhosis as well as emphysema.
High concentrations of the iron carrying protein ferritin are a marker of haemochromatosis.

Condition Autoantibodies Immunoglobulins

Primary High titre of antimitochondrial Raised IgM

Billiary Cirrhosis antibody in 95% of patients

Autoimmune 1) Smooth muscle antibody in 70%, Raised IgG in

Chronic active 2) Antinuclear factors in 60%, all patients.

Hepatitis 3) Low antimitochondrial

Antibody titre in 20%

Primary sclerosing antinuclear cytoplasmic antibody in 30%

Cholangitis

Autoantibodies are a series of antibodies directed against subcellular fractions of various organs, which are released into the circulation when cells are damaged. High titres of antimitochondrial antibodies are specific for primary biliary cirrhosis and antismooth muscle and antinuclear antibodies are often seen in autoimmune chronic active hepatitis. Antibodies against hepatitis are discussed in detail in a future article on hepatitis.

Coagulation

II, V, VII, and IX are synthesised in the liver.

Abnormal clotting (measured as prolongation of the international normalised ratio) occurs in both biliary obstruction and parenchymal liver disease because of a combination of poor absorption of fat-soluble vitamin K (due to absence of bile in the gut) and a reduced ability of damaged hepatocytes to produce clotting factors.

Prothrombin Time

3) Platelet counts

APTTPlatelet Count.

Classification of Common Tests.

General (Non Specific)/Biochemistery

Bilirubin
ALT
AST
ALP
Gamma GT (As for as this remains the earliest finding with other normal liver enzymes, it can be taken as specific due to Alcohalic liver disease. But once the whole spectrum of liver enzymes is disturbed then it looses its specificity.

Specific

Plasma protiens.

Albumin
Globulin

HbSAg

AntiHCV

For practical purposes these two markers shall be ordered to look for viral etiology. If these are negative, then we can forget about viruses as causes of chronic liver disease.if one or both of these are positive then to investigate further viral background other markers have to be looked for. These are discussed in detail in chapter on viral hepatitis.

5 common Viruses

A&E No chronic phase so forget these when looking for chronic viral hepatitis.

B& C Above mentioned two markers are reliable to supect one of these.

D can not be present without B.So If B is negative then D has to be taken as negative.

Essential Knowledge we must have is Gilbert Syndrome

Around 3% population have hyperbilirubinaemia (up to 100 µmol/l, Upto 2mgs) caused by excess unconjugated bilirubin, a condition known as Gilbert's syndrome. These patients have mild impairment of conjugation within the hepatocytes. The condition usually becomes apparent only during a transient rise in bilirubin concentration (precipitated by fasting or illness) that results in frank jaundice. Investigations show an isolated unconjugated hyperbilirubinaemia with normal liver enzyme activities and reticulocyte concentrations. The syndrome is often familial and does not require treatment.

Imaging in Liver and Biliary Disease.

Plain Radiography

Plain radiography has a limited role in the investigation of hepatobiliary disease. Chest radiography may show small amounts of subphrenic gas, abnormalities of diaphragmatic contour and related pulmonary disease, including metastases. Abdominal radiographs can be useful if a patient has calcified or gas containing lesions as these may be overlooked or misinterpreted on Ultrasonography. Such lesions include calcified gallstones (10-15% of gallstones), chronic calcific pancreatitis, gas containing liver abscesses, portal venous gas, and emphysematous cholecystitis.

Ultrasonography

It is the most useful initial investigation in-patients with jaundice. Ultrasonography is the first line imaging investigation in-patients with jaundice, right upper Quadrant pain, or hepatomegaly. It is non-invasive, inexpensive, and quick but requires experience in technique and interpretation. Ultrasonography is the best method for identifying Gallbladder stones and for confirming extrahepatic biliary obstruction, as dilated bile ducts are visible. It is good at identifying liver abnormalities such as cysts and tumours and pancreatic masses and fluid collections, but visualisation of the lower common bile duct and overlying bowel gas often hinders pancreas.

Computed tomography

It is complementary to ultrasonography and provides information on liver texture, gallbladder disease, bile duct dilatation, and pancreatic disease. Computed tomography is particularly valuable for detecting small lesions in the liver and pancreas.

Cholangiography

This identifies the level of biliary obstruction and often the cause. Intravenous cholangiography is rarely used now; as opacification of the bile ducts is poor, particularly in jaundiced patients and anaphylaxis remains a problem. Endoscopic retrograde cholangiopancreatography is advisable when the lower end of the duct is obstructed (by gall stones or carcinoma of the pancreas). The cause of the obstruction (for example, stones or parasites) can sometimes be removed by endoscopic retrograde cholangiopancreatography to allow cytological or histological diagnosis.

Percutaneous transhepatic cholangiography is preferred for hilar obstructions (biliary stricture, cholangiocarcinoma of the hepatic duct bifurcation) because better opacification of the ducts near the obstruction provides more information for planning subsequent management. Obstruction can be relieved by insertion of a plastic or metal tube (a stent) at either endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography.

Magnetic resonance cholangiopancreatography allows non-invasive visualisation of the bile and pancreatic ducts. It is superseding most diagnostic endoscopic cholangiopancreatography, as faster magnetic resonance imaging scanners become more widely available.

Liver Biopsy:

Percutaneous liver biopsy is a day case procedure performed under local anaesthetic.

Indications, Preparation and Complications.

Liver biopsy is essential to diagnose chronic hepatitis and establish the cause of cirrhosis.
When malignancy is suspected in solitary lesions or those confined to one half of the liver, resection is the best way to avoid compromising a potentially curative procedure.

Patients must have a normal clotting time and platelet count
Ultrasonography to ensure that the bile ducts is not dilated.

Complications include bile leaks and haemorrhage.
Overall mortality is around 0.1%.

A transjugular liver biopsy can be performed by passing a special needle, under radiological guidance, through the internal jugular vein, the right atrium, and inferior vena cava and into the liver though the hepatic veins. This has the advantage that clotting time does not need to be normal, as bleeding from the liver is not a problem.

It may cause bleeding (especially with liver cell adenomas), anaphylactic shock (hydatid cysts), or tumour seeding (hepatocellular carcinoma or metastases). Many lesions can be confidently diagnosed by using a combination of imaging methods (ultrasonography, spiral-computed tomography, magnetic resonance imaging, nuclear medicine, laparoscopy, and laparoscopic ultrasonography).

Metabolic Liver Diseases

Genetic haemochromatosis

This is an autosomal recessive disorder of iron metabolism. Excessive iron is absorbed from the gut and deposited in tissues such as the liver, heart, pancreas, anterior pituitary, joints, and skin. This results in end organ damage, which may include cirrhosis and hepatocellular carcinoma. This means that liver disease in affected people can be prevented by early prophylactic treatment with repeated venesection.

For more than 20 years it has been recognised that the gene for genetic haemochromatosis was closely linked to the HLA locus on the short arm of chromosome 6. The precise location has recently been identified; the candidate gene, originally called HLA-H, has been renamed HFE. Tthe discovery of the gene has led to the development of a reliable, simple screening method based on polymer chain reaction techniques.

************************

Wilson's disease

This is a rare, autosomal recessive, inborn error of metabolism. It is characterised by defective biliary copper excretion, which leads to the accumulation of toxic amounts of copper in the liver, brain, kidney, and cornea. Thus far, treatment has been based on chelation of copper with penicillamine to prevent end organ damage or liver transplantation in-patients who present with acute liver failure.

In contrast to genetic haemochromatosis, there does not seem to be a single dominant mutation in the gene for Wilson's disease; most patients have at least two mutant alleles. Owever, analysis of microsatellite markers surrounding the ATP7B Gene enables affected family members to be identified and earlier prophylactic treatment with Penicillamine to be given.

BMJ 2001; 322:1014 (28 April) Quackery in the name of Science.

(Our traditional “JIN”Handlers just have to give some exotic name to their procedures before these are accepted as lawful. PakJFM)

Rebirthing therapy banned after girl died in 70-minute struggle.

Candace Newmaker died during a 70-minute session in which she was wrapped from head to toe and surrounded by pillows. Despite the girl's cries that she was suffocating, the therapists

Continued to push her in an attempt to simulate uterine contractions. The episode had been

Videotaped and was used in court against the therapists, who were convicted of reckless child

Abuse resulting in death and sentenced to 16-48 years' imprisonment.

Candace had been diagnosed with reactive detachment disorder, a psychiatric illness thought to be caused by the failure of normal bonding with a parent or care giver during infancy. The

Disorder shares some features with post-traumatic stress disorder (…Contd on Page no 23)

Liver Transplantation

With the ever increasing discrepancy between the availability of donor organs and the rapidly expanding pool of those needing organs, there has been increasing demand for improved usage of donor organs and new surgical techniques to allow one organ to be used for two different recipients. This has led to the development and refinement in the past few years of auxiliary livers, split livers, and live related donor transplantation.

Auxiliary transplantation,

The left or right lobe of the donor liver is transplanted, while all or Part of the native liver is left in situ. When the native liver has recovered from its initial insult and has regenerated completely, the graft can then be removed or immunosuppressive treatment can be stopped and the graft allowed atrophying. The latter approach is advantageous in that it avoids the need for lifelong immunosuppression and potential drug toxicity.

The largest study to date reports experience with 30 patients who underwent auxiliary liver transplantation for acute liver failure. It found complete regeneration of the native liver with complete withdrawal, or at least a considerable reduction, of immunosuppression in 50% of Patients.

Split liver transplantation

Increased expertise in liver reduction techniques has led to the development of split liver transplantation, where one graft can often be used for an adult recipient and a child. The procedure involves splitting the liver along the principal planes into the anatomical left and right lobes. Considerable surgical precision is then needed to dissect out and divide the arterial, venous, and biliary connections to allow reanastomosis into two different patients. Initial reports of this technique, published in 1988-9, showed poor results at one year only 50% of patients and grafts survived. More recently, a multicentre European study has shown much better outcome.

Live related donor transplantation

Paediatric liver transplantation has expanded rapidly in the past five years. Around 90-100 transplantations are carried out in the United Kingdom each year. Demand for donor organs, which are suitably matched in size, exceeds supply, and the development of live related donor transplantation is one way of correcting the imbalance. With this procedure, a parent donates either the left lobe or left lateral segment of their liver to their child. The procedure allows transplantation to be performed more quickly (almost electively), as there is no need to await a suitable donor organ, and a good quality graft, which has already been screened for disease or transmissible viruses, is ensured. Early graft function is reported to be as high as 94%. Furthermore, the risks of acute and chronic rejection should be reduced in theory because the parent and child have a similar tissue type. If the procedure is carried out by an experienced operator, the potential risks to the donor parent is very low and postoperative liver function should remain normal as the volume of liver removed seldom exceeds 30%-40% of the total. More than 200 of these procedures have now been performed worldwide.

Drug Induced Liver Disease.

From Panel Interview

Antituberculous Therapy.All components of ATT are hepatotoxic. Pyrazinamide is most hepatotoxic, followed by Rifampicin and INH and then Ethumbutol.Whenever there is a problem, drugs should be drawn. If some drug has to be used then it can be introduced later on (once the hepatitis is resolved) in small doses. Dose can be increased slowly.

DESI (traditional medicine) Drugs.This is the second commonest cause of admissions in the hospital for drug induced liver disease. Locally made Alcohalic drinks. Here it is methyl alcohal instead of ethyl alcohal. It can cause severe fulminant hepatitis.

NSAIDS.All are hepatotoxic and can cause acute on chronic hepatitis. Methyl Dopa.It can cause hepatitis and progress to Cirrhosis of Liver, if continued. Other commonly used hepatotoxic drugs include antibiotics, steroids, oral contraceptive and anticonvulsants.

From bmj

The need for vigilance with regard to new drug reactions from conventional agents remains high. However, the increased use of both unconventional therapeutic and recreational drugs has given rise to more recent reports of hepatotoxicity.

Remedies

Herbal remedies have become increasingly popular, and reports of hepatotoxicity induced by these have increased. The spectrum of liver injury ranges

From mild hepatic inflammation to extensive necrosis,
Persistent cholestasis,
Veno-occlusive disease,
Chronic hepatitis,
And even cirrhosis.

Chinese herbal teas, popular for treating dermatitis, are now well recognised as potentially hepatotoxic. Two recent cases reports described jaundice and hepatitis after drinking these teas. The ingredients common to the teas were isolated and analysed. Those found to be hepatotoxic were plant extracts from Dictamnus dasycarpus and Paeonia SP. It is now clear that remedies previously thought to be innocuous are potentially hepatotoxic. Great care should be taken to assess the ingredients before recommending any herbal remedies to patients.

Commonly Used Allopathic Drugs involved in Hepatotoxicity.

Paracetamol /Aspirin/ Non-steroidal anti-inflammatory drugs
Methyldopa /Amiodarone
Monoamine oxidase inhibitors/Phenothiazines (such as chlorpromazine)
Sodium valproate
Oestrogens (oral contraceptives and hormone replacement therapy)

Vanishing Bile Duct Synrome

It describes the progressive destruction of segments of the intrahepatic biliary tree that is caused by a number of agents. It results in the disappearance of intrahepatic bile ductules and the development of long lasting cholestasis. At least 30 drugs have now been reported as causes of this phenomenon. Even though the offending agent is stopped, there is usually chronic cholestasis, often with jaundice, and high alkaline phosphatase and glutamyltranspeptidase activities for more than one year.

Ajmaline derivatives Cyamemazine Erythromycin esters

Arsenicals Flucloxacillin Carbamazepine

Methyltestosterone Chlorpromazine Phenytoin

Co-trimoxazole Prochlorperazine

Aceprometazine Haloperidol Amineptine

Ibuprofen Amitriptyline Imipramine

Ampicillin Norandrostenolone Azathioprine

Oestradiol Barbiturates Tetracyclines

Carbutamide Thiabendazole Chlorothiazide

Tiopronin Cimetidine Tolbutamide

Clindamycin Trimethoprim-sulphamethoxazole

Cyclohexylpropionate Trioleandomycin Cyproheptatine

Xenalamine Glycyrrhizin

BMJ 2001; 322:1079-1080 (5 May)/Editorials

The burden of musculoskeletal conditions 2000-2010=Bone and Joint Decade.

The burden is huge and not reflected in national health priorities. Musculoskeletal conditions have an enormous and growing impact worldwide. "Health 21," the health for all policy framework for the World Health Organization's European region, identifies musculoskeletal conditions as a target, yet national health care priorities in the United Kingdom and most European countries do not include them. To address this imbalance the United Nation, the WHO, governments, and professional and patients’ organisations have declared 2000-10 the "bone and joint decade" with the aim of improving the health related quality of life of people with musculoskeletal conditions.

Acute Liver Failure.

In the past five years improvements in intensive care management, with earlier recognition of the need to transfer patients to specialist liver units, have led to an overall reduction in mortality.

Use of

Early elective ventilation for encephalopathy
Prophylactic antibiotics and antifungal agents.
Inotropic support.
Renal support with dialysis.
N-acetylcysteine infusion.
Intracranial pressure monitoring

Have all played their part in improved survival.

-Acetylcysteine infusion

N-acetylcysteine infusion, a well-established treatment in toxicity induced by paracetomol, is now used selectively to treat other forms of acute liver failure. The considerable experience of King's College Hospital in treating patients with paracetamol toxicity and liver failure between 1987 and 1993 was reported recently. Survival improved from 50% to 75% as the frequency of N-acetylcysteine administration increased from 40% to 83%.

New technologies without liver transplantation, the survival of patients with acute liver failure are 60% at best. Other forms of artificial liver support are therefore needed to allow spontaneous recovery or to sustain the patient awaiting transplantation. Current work has centered on bioartificial liver devices, two of which have recently undergone clinical trials. Both the Extracorporeal Liver Assist device and the Bioartificial Liver device use hepatocytes and have the potential to provide artificial metabolic and synthetic liver function in acute liver failure. Experimental and early clinical data suggest that transplantation of hepatocytes may be of benefit in acute liver failure.

…Contd from page no 16. Quackery in the name of Science in USA.

And borderline personality disorder. People at risk include adopted children and those who have been institutionalised. Though uncommon, it is being diagnosed with increasing frequency, and 40 centres around the United States have sprung up specialising in its treatment.

The disorder is characterised by difficulties in establishing and maintaining trusting relationships and by emotional disturbances in social situations. It starts before the age of 5 years. Symptoms include failure to establish eye contact, persistent lying and stealing, poor impulse control, cruelty to animals, and a seeming lack of conscience. Both inhibited and disinhibited types occur. The inhibited type avoids tactile contact, is resistant to comforting and is hypervigilant, while the disinhibited type may be engaging and form superficial relationships with strangers.

Conventional treatment for the disorder relies on intensive psychotherapy with the patient and family, as well as "holding therapy" in which the patient is hugged, held, and cuddled by the therapist and care giver(s).

In the case of Candace Newmaker, "rebirthing therapy" was used. Traditional rebirthing therapy is itself a fringe treatment and was developed in the 1970s by Leonard Orr, a psychotherapist. It is predominantly a breathing technique and rarely lasts more than 15 minutes. Her therapists, social workers Connell Watkins and Julie Ponder, and two assistants restrained the girl. Ultimately, they crushed her with a combined weight of 304 kg, continually taunting her and exhorting her to squeeze through and be reborn. When Candace Newmaker was unwrapped she was cyanotic and apnoeic. Cardiopulmonary resuscitation was started but the girl died the next day. A postmortem examination gave the cause of death as asphyxiation.