Guillain Barre Syndrome (GBS)

Guillain-Barre syndrome (GBS) is a disorder in which the body's immune system attacks part of the peripheral nervous system - an acute form of immune-mediated polyneuropathy. It’s also called as Landry's paralysis as it was first described by the French physician Jean Landry in 1859. It can cause life-threatening complications, in particular if the respiratory muscles are affected or if there is autonomic nervous system involvement.

GBS can be further classified into two major subtypes based on electrophysiological and pathological findings:

Causes

No one yet knows why Guillain-Barré — which is not contagious — strikes some people and not others.

In Guillain-Barré syndrome, the immune system starts to destroy the myelin sheath that surrounds the axons of many peripheral nerves, or even the axons themselves (axons are long, thin extensions of the nerve cells which carry nerve signals). In diseases in which the peripheral nerves' myelin sheaths are injured or degraded, the nerves cannot transmit signals efficiently. That is why the muscles begin to lose their ability to respond to the brain's commands which must be carried through the nerve network.

Often people get GBS after having a cold or the flu and sometime after vaccination or surgery. It is also possible that the virus makes the immune system itself less discriminating about what cells it recognizes as its own, allowing some of the immune cells, such as certain kinds of lymphocytes, to attack the myelin. In two forms of GBS, axons are attacked by antibodies against the bacteria Campylobacter jejuni, which react with proteins of the peripheral nerves.

Prevalence

The syndrome is rare affecting only about 1 person in 100,000. It can strike at any age and with men to women ratio of 1.78. The incidence increases with age; there are approximately 1 cases per 100,000 people aged below 30 years and about 4 cases per 100,000 in those older than 75 years. The incidence of GBS during pregnancy is 1.7 cases per 100,000 of the population.

Signs & Symptoms

Usually Guillain-Barré occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal infection. After the first clinical manifestations of the disease, the symptoms can progress over the course of hours, days, or weeks.

• Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear. By the third week of the illness, 90% of all patients are at their weakest.

• Ascending Paralysis - weakness or tingling sensations - in the legs is the first symptom then it will spread toward arms and upper body. These symptoms can increase in intensity until certain muscles cannot be used at all and, when severe, the person is almost totally paralyzed.

• Muscle pain or difficulty moving your legs, arm, or face

• Constipation or difficulty controlling your urine or bowel movements

• Blurred vision or dizziness

• Proprioception (position sense)

• Areflexia (complete loss of deep tendon reflexes)

• Loss of Sensation (Pain and Temperature)

• Sudden paralysis

In some cases, the disorder is life threatening - potentially interfering with breathing and, at times, with blood pressure or heart rate - and is considered a medical emergency.

Most individuals, however, recover from even the most severe cases of Guillain-Barré syndrome, although some continue to have a certain degree of weakness.

Diagnosis

Several disorders have symptoms similar to those found in Guillain-Barré syndrome. So doctors examine and question patients carefully before making a diagnosis including neurologic examination, check your reflexes and how your pupils react to light. They may check your memory, hand grasp, and balance. Collectively, the signs and symptoms form a certain pattern that helps doctors differentiate Guillain-Barré from other disorders.

• Symptoms appear on both sides of the body (most common in Guillain-Barré)

• Quickness with which the symptoms appear

• In Guillain-Barré, reflexes such as knee jerks are usually lost.

  • Blood and Urine Tests: to find the cause of symptoms and also be used to make sure organs, such as your liver and kidneys, are working correctly.

  • Lumbar puncture (Spinal Tap): A needle is inserted into the patient's lower back and a small amount of Cerebrospinal Fluid (CSF) from the spinal column is withdrawn. In cerebrospinal fluid, characteristic findings include albumino-cytological dissociation. As opposed to infectious causes, this is an elevated protein level (100–1000 mg/dL), without an accompanying increased cell count (absence of pleocytosis).

  • Electromyography (EMG): to test the function of muscles and the nerves control that muscle. Needles attached with Electrodes (wires) are inserted into muscle and the electrical activity of muscles and nerves is measured at rest and with activity.

  • Nerve Conduction Studies (NCS):To measure how nerves respond to stimulation. Electrodes (wires), placed on affected areas, send electrical currents into the nerve to see how quickly it responds.

Treatment

There is no cure for GBS, but therapies can lessen the severity of the illness and accelerate the recovery in most patients. There are also a number of ways to treat the complications of the disease.

• Immune Globulins (IVIg): Decreases damage to your nerves. In immunoglobulin therapy, doctors give intravenous injections of the proteins that in small quantities, the immune system uses naturally to attack invading organism.

  • IVIg is indicated in treatment of GBS including GBS variants (Miller-Fisher syndrome [MFS], pan-autonomic polyneuropathy, acute pan-dysautonomia, acute motor axonal neuropathy [AMAN], and acute motor and sensory axonal neuropathy [AMSAN]) with significant weakness such as inability to stand or walk without aid, respiratory or bulbar weakness diagnosed during the first 2 weeks of the illness.

  • Plasma exchange (also called “plasmapheresis”): For this treatment, a machine pumps blood from the body and removes substances from the blood that are attacking the nervous system. Then the machine returns the blood to the body

  • Ventilator: for breathing in emergency.

  • Supportive medications: blood thinners, cardiac Medicine, pain relieving medicine and stool softeners

The most critical part of the treatment for this syndrome consists of keeping the patient's body functioning during recovery of the nervous system. This can sometimes require placing the patient on a ventilator, a heart monitor, or other machines that assist body function.

Prognosis

The recovery period may be as little as a few weeks or as long as a few years. About 30% of those with Guillain-Barré still have a residual weakness after 3 years. About 3% may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack. It has a serious long-term impact on the patients’ work and private life, even 3–6 years after the onset of illness. Recovery can be slow and take years.

Kawasaki Disease

Kawasaki disease (KD), also called Mucocutaneous Lymph Node Syndrome (MCLS), is one of the most common vasculitides of childhood. KD also occurs rarely in adults. It is typically a self-limited condition, with fever and manifestations of acute inflammation lasting for an average of 12 days without therapy.

However, complications such as coronary artery aneurysms, depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion may develop and lead to significant morbidity and mortality.

Causes & Risk Factors

KD is the most common vasculitides of childhood, particularly in East Asia. The underlying etiology is unknown.

Possible Risk Factors

• Immunologic Response

• Infectious Etiology

• Genetic Factors

• Family History

• Race: Children from Asian countries, such as Japan, are at higher risk

• Skin Disorder like eczema

Prevalence

The incidence of KD is greatest in children who live in East Asia or are of Asian ancestry living in other parts of the world. The incidence in underdeveloped countries is largely unknown and ascertainment may be incomplete. Many nations around the world have demonstrated an increase in the number of children diagnosed with KD since the early to mid 2000s.

In Japan, there is a reported 10-fold increased risk of KD for children with an affected sibling and a twofold increased risk for those with a previously affected parent. In North America, there are cases reports of families with multiple affected members.

Boys are affected more commonly than girls. 80-90 % of cases occur in children younger than five, although KD is relatively uncommon among children younger than six months. Occurrence beyond late childhood is rare.

Signs & Symptoms

The clinical features of KD reflect widespread inflammation of medium and small-sized blood vessels. Diagnosis is based upon evidence of systemic inflammation, as evidenced by fever, in association with signs of mucocutaneous inflammation. Symptoms include:

• Fever

• Redness in the white part of the eye

• Cracked, red lips

• A red, swollen tongue

• Rash starting in the genital area but can be on the back, chest, belly, arms, and legs.

• Swollen glands in the neck

• Swollen, red skin on the palms of the hands and soles of the feet

Diagnosis

Guidelines for the diagnosis of KD were established by Tomisaku Kawasaki in 1967. Diagnosis of KD according to these criteria requires the presence of fever lasting ≥five days, combined with at least four of the five following physical findings, without an alternative explanation:

• Bilateral bulbar conjunctival injection

• Oral mucous membrane changes, including injected or fissured lips, injected pharynx, or strawberry tongue

• Peripheral extremity changes, including erythema of palms or soles, edema of hands or feet (acute phase) and periungual desquamation (convalescent phase)

• Polymorphous rash

• Cervical Lymphadenopathy (at least one lymph node >1.5 cm in diameter)

Redness or crust formation at the site of Bacille Calmette-Guerin (BCG) inoculation is also suggested as a useful sign in several diagnostic guidelines.

Laboratory Findings

• Systemic inflammation is characteristic of KD. Typical manifestations include elevation of acute phase reactants (e.g. increased C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]), increase in white blood cell counts, and a left-shift in the white blood cell count. Platelet counts generally rise by the second week of illness and may reach 1,000,000/mm³ (reactive thrombocytosis) in the most severe cases.

• Children with KD often present with anemia.

• Urinary microscopy commonly reveals white blood cells.

• Abnormal Liver Function Test

• Cerebrospinal fluid (CSF) may display a mononuclear pleocytosis without hypoglycorrhachia or elevation of CSF protein

• Significant perturbations in serum lipid profiles, including elevated triglycerides and low density lipoproteins, and depressed high density lipoproteins

• Increase serum sodium level

Treatment

Theoretically, it should be possible to stratify therapy for KD according to disease severity defined by the likelihood of developing CA aneurysms. While many risk scores have been proposed, none are validated across different populations. Since no criteria have been developed that can reliably identify children most at risk for severe disease at the time of initial presentation, all children diagnosed with KD are treated at the time of diagnosis.

Treatment Options

• Intravenous Immune Globulin

• Aspirin

• Glucocorticoids

• TNF-alpha agents (Etanercept, Infliximab, etc.)

Prognosis

With early recognition and treatment, full recovery can be expected. The reported mortality rate of KD is low (0.1 to 0.3 percent). Children without cardiovascular abnormalities detected in the acute and subacute phase (up to eight weeks after onset of disease) appear to be clinically asymptomatic 10 to 21 years later. Patients who have had KD should have an echocardiogram every 1 - 2 years to screen for heart problems. There appears to be a low rate of recurrence for KD as illustrated by data from the 13th and 14^th nationwide surveys of Kawasaki disease in Japan.

Children generally do not feel completely well for several weeks after KD, and they therefore tend to limit their own activity level. Restrictions are dependent on the risk of myocardial infarction and should be imposed only in children with increased risk of thrombosis during the convalescent stage of disease, particularly those with giant coronary artery (CA) aneurysms.

Immunodeficiency Syndrome

Immune system function is altered by many conditions which primarily impair function of other organ systems. They can be classified as primary or secondary.

Primary immunodeficiency syndromes

• Mostly these are inherited/congenital gene disorders that present in infancy or in early childhood. Mutations of genes governing immune system functions have been identified and over 150 such disorders have been identified. The overall incidence of symptomatic primary immunodeficiency is estimated to be 1/10,000. 70% occur in males due to X-linked inheritance in many syndromes.

• IVIg therapy is the mainstay of treatment for a variety of primary immune deficiency states.

Secondary Immunodeficiency syndromes

Secondary immunodeficiencies, also known as acquired immunodeficiencies can be caused by many diseases directly or indirectly cause immunosuppression. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV).

IVIg is used as replacement therapy in secondary Immunodeficiency in patients with chronic lymphocytic leukaemia (CLL) or multiple myeloma (MM) with recurrent infections and paediatric HIV patients who have bacterial infections.

Relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) that is a leading cause of disability in young adults. Relapsing-remitting MS (RRMS) is characterized by clearly defined relapses with full recovery or with sequelae and residual deficit upon recovery. There is no disease progression during the periods between disease relapses.

IVIg is used in the treatment of severe manifestations of relapsing-remitting MS (where standard therapy have failed.

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is a non-vasculitic inflammatory demyelinating condition with a striking clinical and pathological resemblance to multiple sclerosis (MS).

IVIG may be considered medically necessary in persons with acute disseminated encephalomyelitis who have an insufficient response to intravenous corticosteroid treatment.

Refractory Dermatomyositis/ Refractory Polymyositis

Dermatomyositis is an idiopathic inflammatory myopathy, with characteristic cutaneous findings, that occurs in children and adults. This systemic disorder most frequently affects the skin and muscles with eruption on exposed surfaces, pruritus of skin lesions, proximal muscle weakness and muscle tenderness as presenting symptoms. Polymyositis is an idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness; elevated skeletal muscle enzyme levels; and characteristic electromyography (EMG) and muscle biopsy findings.

IVIG is used in the treatment of refractory severe dermatomyositis and refractory polymyositis.

Hemolytic Disease of the Newborn

Hemolytic Disease of the Newborn (HDN), also known as erythroblastosis fetalis, isoimmunization, or blood group incompatibility, occurs when fetal red blood cells (RBCs), which possess an antigen that the mother lacks, cross the placenta into the maternal circulation, where they stimulate antibody production. The antibodies return to the fetal circulation and result in RBC destruction.

In infants with isoimmune hemolytic disease and rising TB despite intensive phototherapy, administration of intravenous immunoglobulin (IVIG) is recommended since it may avoid the need for exchange transfusion.

Lambert-Eaton Myasthenic Syndrome (LEMS)

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes.

IVIg is used in the treatment of severe Lambert-Eaton Myasthenic Syndrome (LEMS) unresponsive to medical therapy.

Chronic parvovirus B19 Infection with Severe Anemia(Pure Red Cell Aplasia)

Parvovirus B19 (B19V) is a single-stranded DNA virus of the family Parvoviridae. Infections with this virus is quite common, and in most cases, usually mild or asymptomatic, and do not require treatment. In some cases, however, infection is associated with sufficiently severe complications like transient aplastic crisis, fetal hydrops, chronic infection with or without anemia where treatment is indicated and may be lifesaving.

IVIg can be used for treatments for HIV-infected individuals with pure red cell aplasia related to B19 coinfection at doses of 1 to 2 grams/kg/day for two to five days. Relapses in these patients can be successfully treated with maintenance IVIG at doses of 0.4 grams/kg/day every four weeks.

Post-transfusion purpura

Post-transfusion purpura is a rare, life-threatening syndrome that can develop in an individual who lacks the HPA-1a (Pl[A1]) platelet antigen. Severe thrombocytopenia develops approximately one week after transfusion with HPA-1-positive blood.

IVIg (500 mg/kg per day for two consecutive days) results in a much more rapid recovery (ie, four days to reach platelet counts greater than 100,000/µL).

Renal transplantation

IVIg is an important component of different desensitization regimen for performing renal transplantation from live donor with ABO incompatibility or positive cross-match.

It is also indicated in solid organ transplantation, for suppression of panel reactive anti-HLA antibodies in persons with high panel reactive antibody (PRA) levels to human leukocyte antigens (HLA) prior to transplantation, and for treatment of antibody mediated rejection of solid organ transplants.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an acquired disorder of peripheral nerves and nerve roots. The disorder is sometimes called chronic relapsing polyneuropathy or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots). CIDP is closely related to Guillain-Barré syndrome and it is considered the chronic counterpart of that acute disease.

Causes

Although the cause of CIDP and its variants is unknown, there is evidence to support the hypotheses that the disorder(s) are immunologically based and have multiple triggers. CIDP leads to a common type of damage to nerves outside the brain or spinal cord (peripheral neuropathy). It usually affects both sides of the body.

It may occur with other conditions, such as:

Idiopathic Thrombocytopenic Purpura

Idiopathic Thrombocytopenic Purpura (also called Immune Thrombocytopenia, Immune Thrombocytopenic Purpura, ITP) is an acquired disorder. There is marked interpatient variability in the clinical presentation of ITP. Although the onset of ITP may be acute and abrupt, it is more often insidious.

The pathogenesis of ITP is related to increased platelet destruction and inhibition of megakaryocyte platelet production (via the production of specific IgG autoantibodies by the patient's B cells).

Causes & Risk Factors

The etiology of ITP is unclear, but is thought to include genetic as well as acquired factors:

• Preceding viral infection

• Alterations in the immune response which might promote the development of self-reactive antibodies.

• Pre-existing autoimmune diseases like antiphospholipid syndrome, systemic lupus erythematosus, Evans syndrome

• Viral or bacterial infections (like Helicobacter pylori infection, Virus-specific antibodies, HIV & HCV and Bacterial products, such as lipopolysaccharides)

• Drugs like Alemtuzumab, Purine analogs or quinine-containing beverages, foods, and herbal remedies have been associated with the development of autoimmune disorders.

Prevalence

ITP is a common acquired bleeding disorder. The incidence of ITP in children is greater than the incidence among adults. In children, the incidence of ITP in boys and girls is similar. Many reports have suggested that, among adults with ITP, approximately 70 percent are women and 72 percent of these women are less than 40 years of age.

This is an important issue since, in two large case series, 18 percent and 29 percent of adults were discovered to have ITP when they had no bleeding symptoms. Therefore, the total incidence of ITP among adults is likely to be greater than 22 per million per year.

Signs & Symptoms

The clinical manifestations of ITP are limited to those related to excessive bleeding caused by thrombocytopenia. The bleeding manifestations of thrombocytopenia are described as mucocutaneous, to distinguish them from the delayed, slowly evolving visceral hematomas characteristic of coagulation disorders such as haemophilia. Thus, in patients with thrombocytopenia due to ITP:

• Petechiae, purpura, and easy bruising are expected.

• Epistaxis, gingival bleeding, and menorrhagia are common.

• Overt gastrointestinal bleeding and gross hematuria are rare.

• Nosebleed or bleeding in the mouth

• Intracranial hemorrhage, a potentially fatal bleeding complication, is so uncommon that there is no reliable estimate of its frequency.

The clinical manifestations of thrombocytopenia also vary with age.

Diagnosis

There is no "gold standard" test that can establish the diagnosis of ITP. The diagnosis is, in part, one of exclusion, requiring that other causes of thrombocytopenia be ruled out.

There are many criteria required in order to make this diagnosis

• Peripheral Blood Smear Test

• Antiplatelet antibody testing

• Clinically apparent associated conditions (e.g., systemic lupus erythematosus, antiphospholipid syndrome, chronic lymphocytic leukemia and other lymphoproliferative disorders) are not present.

• A complete blood count (CBC) shows a low number of platelets.

• Blood clotting tests (PTT and PT) are normal.

• Bleeding time is prolonged.

Further tests like HIV and HCV infection tests, Thyroid Function Test, Bone marrow Aspiration/Biopsy, etc. can also be performed for presumptive diagnosis.

Treatment

Major bleeding is rare in patients with ITP, primarily occurring in those with platelet counts below 10,000/µL. The goal for treatment of ITP is to provide a safe platelet count to prevent major bleeding, rather than returning the platelet count to normal.

Initial Treatment

• Glucocorticoids(Prednisolone, Dexamethasone, Methylprednisolone)

• Intravenous Immune Globulin

• Anti-Rh(D) Therapy

Second line Management

Second-line management should be reserved for patients with persistent symptomatic thrombocytopenia following treatment with Glucocorticoids. Treatment options are:

• Splenectomy

• Rituximab (alone or in combination)

• Thrombopoiesis-stimulating agents (e.g. Romiplostim and Eltrombopag)

Although rare, intracerebral bleeding, severe gastrointestinal bleeding, and death from bleeding can occur in ITP. Life-threatening bleeding may be seen at any age and at any time during the course of this disease, but appears to be more common in older patients. In such condition Platelet transfusions, Factor VIIa, etc. could be the option.

IVIg is indicated in the treatment of adult patients with severe thrombocytopenia (platelet counts less than 20,000/µL) considered to be at risk for intra-cerebral hemorrhage OR management of acute bleeding due to severe thrombocytopenia (platelet counts less than 30,000/µL).

IVIg is indicated in the treatment of pediatric patients as initial therapy of acute ITP if platelet count is less than 20,000/µL with emergency bleeding or is at risk for severe life-threatening bleeding; or patients with severe thrombocytopenia (platelet counts less than 20,000/µL) considered to be at risk for intra-cerebral hemorrhage.

Prognosis

The mortality of ITP in published case series ranges from 0.3 to 5 percent, consistent with the estimated frequency of intracranial hemorrhage. With treatment, the chance of remission (a symptom-free period) is good. Rarely, ITP may become a long-term condition in adults and reappear, even after a symptom-free period.

Hematopoietic Stem Cell Transplant (HSCT) or Bone Marrow Transplant (BMT)

IVIG is considered medically necessary for prophylaxis in allogeneic or syngeneic transplant recipients within the first 100 days post-transplant; after 100 days post-transplant IVIG is indicated for treatment of recipients who are markedly hypogammaglobulinemic (IgG level less than 400 mg/dL) or who have CMV, EBV, or RSV infection.

IVIG is considered medically necessary for steroid-resistant graft-versus-host disease in BMT recipients 20 years of age or older, in the first 100 days post transplant, and who are hypogammaglobinemic (IgG level less than 400 mg/dL).

Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies form against nicotinic acetylcholine (ACh) postsynaptic receptors at the neuromuscular junction (NMJ) of the skeletal muscles resulting in a characteristic pattern of progressively reduced muscle strength with repeated use and recovery of muscle strength after a period of rest. The most important aspect of MG in emergency situations is acute worsening of weakness leading to respiratory failure.

IVIg is recommended for treatment of acute myasthenic crisis with decompensation (respiratory failure, or disabling weakness requiring hospital admission); and when other treatments have been unsuccessful or are contraindicated.

Autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is caused by autoantibody-induced hemolysis (the premature destruction of circulating red blood cells); usually idiopathic, it is also associated with infection, lymphoproliferative disorders, autoimmune diseases, and some drugs. Hallmark findings include: anemia with elevated reticulocyte count in the absence of blood loss; a positive direct antiglobulin (Coombs) test; and spherocytes or RBC aggregates on the peripheral blood smear. It is classically divided into two groups: warm and cold disease.

IVIG may be considered medically necessary in persons with warm-type autoimmune hemolytic anemia that does not respond to corticosteroids or splenectomy, or those for whom the latter two treatments are contraindicated.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT)

It is a disease that affects fetuses and newborns, in which the platelet count is decreased by antibodies specific for platelet antigens inherited from the father but which are absent in the mother which result in the recognition of these antigens by the mother's immune system as non-self, with the subsequent generation of allo-reactive antibodies which cross the placenta.

IVIG is indicated in the treatment at 20 weeks or later when cordocentesis reveals fetal platelets less than 20000/mL or previous pregnancy affected by FAIT.

Hyperimmunoglobulin E Syndrome (Job Syndrome; Hyper IgE syndrome)

Hyperimmunoglobulin E syndrome is now recognized as a primary immunodeficiency disease characterized by recurrent skin abscesses, recurrent pneumonica with pneumotocele, eczematous dermatitis, and elevated serum IgE levels.

Multifocal Motor Neuropathy with Conduction Block

It is an acquired immune-mediated demyelinating neuropathy with slowly progressive weakness, fasciculations, and cramping, without significant sensory involvement. Clinically, it may resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but muscle atrophy and more rapid progression are lacking.

IVIG infusions are the mainstay of MMN treatment. Patients are initially treated with IVIG (2 g/kg) over 2-5 days, followed by maintenance infusions. The frequency of maintenance treatments depends on patients' symptoms, and it is usually every 4-8 weeks.

Autoimmune Mucocutaneous Blistering Diseases

Autoimmune blistering diseases (AIBD) are a rare group of diseases that affects the skin and mucous membranes. They tend to be chronic remitting conditions This category includes various dermatological conditions like Pemphigus vulgaris, Pemphigus foliaceus, Bullous Pemphigoid, Mucous Membrane Pemphigoid (a.k.a. Cicatricial Pemphigoid), and Epidermolysis bullosa acquisita.

IVIg is used in the treatment of rapidly progressing, extensive or debilitating autoimmune mucocutaneous blistering diseases where with established diagnosis and resistant/intolerant to other standard treatments

Stem cell or bone marrow transplantation

IVIG is indicated for prophylaxis in allogeneic or syngeneic transplant recipients within the first 100 days post-transplant; after 100 days post-transplant IVIG is indicated for recipients who are markedly hypogammaglobinemic (IgG level less than 400 mg/dL), or who have CMV, EBV, or RSV infection.

IVIG is also indicated for steroid-resistant graft-versus-host disease in bone marrow transplant recipients 20 years of age or older, in the first 100 days post-transplant, and who are hypogammaglobinemic (IgG level less than 400 mg/dL).