Criteria for the Diagnosis of Asthma

Asthma is a chronic inflammatory disease of the airways that is characterized by variable narrowing of the airways and symptoms of intermittent dyspnea, wheezing, and nighttime or early-morning coughing.

Criteria for the Diagnosis of Asthma

Presence of episodic symptoms of airflow obstruction or airway hyperresponsiveness
Objective assessment consisting of one of the following

Airflow obstruction that is at least partially reversible with the use of an inhaled short-acting beta 2-agonist, as shown by one of three variables

An increase in FEV1 of >/=12% from baseline
An increase in predicted FEV1 of >/=10 percentage points from baseline
An increase in PEF of >/=20% (or 60 liters/min) from baseline

Diurnal variation in PEF (measured twice daily) of more than 10%

* FEV1 denotes forced expiratory volume in 1 second, and PEF peak expiratory flow.

References:

1. Bel EH. Clinical Practice. Mild asthma. N Engl J Med. 2013 Aug 8;369(6):549-57.[Medline]
2. Mintz M. Asthma update: part I. Diagnosis, monitoring, and prevention of disease progression. Am Fam Physician. 2004;70:893-898. [Medline]

Intravenous Immune Globulin in Autoimmune and Inflammatory Diseases

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulins (IVIg) have increasingly been used as immunomodulatory agent in autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic, probably involving Fc-dependent and/or F(ab')2-dependent non-exclusive mechanisms of action. IVIg broadly interacts with the different components of the immune system: cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also has an impact on effector functions of immune cells. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis.

Diseases for Which Intravenous Immune Globulin Has Been Shown to Be Beneficial

FDA-approved indications

• Primary immunodeficiency disease
• Chronic lymphocytic leukemia
• Pediatric HIV infection
• Kawasaki’s disease
• Allogeneic bone marrow transplantation
• Chronic inflammatory demyelinating polyneuropathy
• Kidney transplantation involving a recipient with a high antibody titer or an ABO-incompatible donor
• Multifocal motor neuropathy

Additional approved indications with criteria

Neuromuscular disorders

• Guillain–Barré syndrome
• Relapsing–remitting multiple sclerosis
• Myasthenia gravis
• Refractory polymyositis
• Polyradiculoneuropathy
• Lambert–Eaton myasthenic syndrome
• Opsoclonus–myoclonus
• Birdshot retinopathy
• Refractory dermatomyositis

Hematologic disorders

• Autoimmune hemolytic anemia
• Severe anemia associated with parvovirus B19
• Autoimmune neutropenia
• Neonatal alloimmune thrombocytopenia
• HIV-associated thrombocytopenia
• Graft-versus-host disease
• Cytomegalovirus infection or interstitial pneumonia in patients undergoing bone marrow transplantation

Dermatologic disorders

• Pemphigus vulgaris
• Pemphigus foliaceus
• Bullous pemphigoid
• Mucous-membrane (cicatricial) pemphigoid
• Epidermolysis bullosa acquisita
• Toxic epidermal necrolysis or Stevens–Johnson syndrome
• Necrotizing fasciitis

* This is an abbreviated list of conditions approved under Medicare Part D or Aetna Clinical Policy Bulletin (2012). Criteria include medical certainty of diagnosis, medical necessity owing to the failure of usual treatments, contraindications to usual treatments, rapid progression or relapse, documentation of progress, and attempts to adjust drug dosages without improvement. FDA denotes Food and Drug Administration, and HIV human immunodeficiency virus.

References:

1. Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012 Nov 22;367(21):2015-25. [Medline]
2. Jolles S, Sewell WA, Misbah SA. Clinical uses of intravenous immunoglobulin. Clin Exp Immunol. 2005 Oct;142(1):1-11. [Medline]

Diagnostic Criteria for Chronic HBV Infection

Chronic HBV infection is a necroinflammatory disease of the liver caused by persistent infection with HBV, and can be categorized as hepatitis B e antigen (HBeAg) positive or negative. Inactive hepatitis B surface antigen (HBsAg) carriers have HBV infection of the liver without significant, ongoing necroinflammatory disease. HBV infection is resolved when there is no further virologic, biochemical, or histologic evidence of active viral infection or disease.

Diagnostic criteria related to HBV include the following:

• Chronic hepatitis B: HBsAg positive for more than six months, serum HBV DNA greater than 20,000 IU per mL (lower values of 2,000 to 20,000 IU per mL often occur with HBeAg-negative chronic hepatitis B), persistent or intermittent elevation in alanine transaminase (ALT) or aspartate transaminase (AST) levels, and liver biopsy showing chronic hepatitis with moderate or severe necroinflammation.
• Inactive HBsAg carrier state: HBsAg positive for more than six months, HBeAg negative and anti-HBeAg positive, serum HBV DNA less than 2,000 IU per mL, persistently normal ALT and AST levels, liver biopsy confirming absence of significant hepatitis.
• Resolved hepatitis B: known history of acute or chronic hepatitis B or the presence of anti-hepatitis B core antigen (anti-HBcAg) with or without anti-HBsAg, HBsAg negative, undetectable serum HBV DNA (very low levels may be detectable with sensitive prostate-specific antigen assays), and normal ALT levels.

References:

1. Kuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012 May;16(2):347-69.[Medline]
2. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373:582–92. [Medline]
3. Bonino F, Piratvisuth T, Brunetto MR, Liaw YF. Diagnostic markers of chronic hepatitis B infection and disease. Antivir Ther. 2010;15 Suppl 3:35-44. [Medline]

Revised Diagnostic Criteria for Rett Syndrome (RTT)

Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2).

Revised diagnostic criteria for RTT.

RTT Diagnostic Criteria 2010

• Consider diagnosis when postnatal deceleration of head growth observed.

Required for typical or classic RTT

1. A period of regression followed by recovery or stabilization*
2. All main criteria and all exclusion criteria
3. Supportive criteria are not required, although often present in typical RTT

Required for atypical or variant RTT

1. A period of regression followed by recovery or stabilization*
2. At least 2 out of the 4 main criteria
3. 5 out of 11 supportive criteria

Main Criteria

1. Partial or complete loss of acquired purposeful hand skills.
2. Partial or complete loss of acquired spoken language**
3. Gait abnormalities: Impaired (dyspraxic) or absence of ability.
4. Stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms

Exclusion Criteria for typical RTT

1. Brain injury secondary to trauma (peri- or postnatally), neurometabolic disease, or severe infection that causes neurological problems***
2. Grossly abnormal psychomotor development in first 6 months of life#

Supportive Criteria for atypical RTT##

1. Breathing disturbances when awake
2. Bruxism when awake
3. Impaired sleep pattern
4. Abnormal muscle tone
5. Peripheral vasomotor disturbances
6. Scoliosis/kyphosis
7. Growth retardation
8. Small cold hands and feet
9. Inappropriate laughing/screaming spells
10. Diminished response to pain
11. Intense eye communication - “eye pointing”

*Because MECP2 mutations are now identified in some individuals prior to any clear evidence of regression, the diagnosis of “possible” RTT should be given to those individuals under 3 years old who have not lost any skills but otherwise have clinical features suggestive of RTT. These individuals should be reassessed every 6–12 months for evidence of regression. If regression manifests, the diagnosis should then be changed to definite RTT. However, if the child does not show any evidence of regression by 5 years, the diagnosis of RTT should be questioned.

**Loss of acquired language is based on best acquired spoken language skill, not strictly on the acquisition of distinct words or higher language skills. Thus, an individual who had learned to babble but then loses this ability is considered to have a loss of acquired language.

***There should be clear evidence (neurological or ophthalmological examination and MRI/CT) that the presumed insult directly resulted in neurological dysfunction.

#Grossly abnormal to the point that normal milestones (acquiring head control, swallowing, developing social smile) are not met. Mild generalized hypotonia or other previously reported subtle developmental alterations during the first six months of life is common in RTT and do not constitute an exclusionary criterion.

##If an individual has or ever had a clinical feature listed it is counted as a supportive criterion. Many of these features have an age dependency, manifesting and becoming more predominant at certain ages. Therefore, the diagnosis of atypical RTT may be easier for older individuals than for younger. In the case of a younger individual (under 5 years old) who has a period of regression and >/=2 main criteria but does not fulfill the requirement of 5/11 supportive criteria, the diagnosis of “probably atypical RTT” may be given. Individuals who fall into this category should be reassessed as they age and the diagnosis revised accordingly.

References:

1. Jeffrey L. Neul, Walter E. Kaufmann, Daniel G. Glaze, John Christodoulou, Angus J. Clarke, Nadia Bahi-Buisson, Helen Leonard, Mark E. S. Bailey, N. Carolyn Schanen, Michele Zappella, Alessandra Renieri, Peter Huppke, Alan K. Percy. Rett Syndrome: Revised Diagnostic Criteria and Nomenclature. Ann Neurol. 2010 December; 68(6): 944–950. [Medline]
2. Percy AK, Neul JL, Glaze DG, Motil KJ, Skinner SA, Khwaja O, Lee HS, Lane JB, Barrish JO, Annese F, McNair L, Graham J, Barnes K. Rett syndrome diagnostic criteria: lessons from the Natural History Study. Ann Neurol. 2010 Dec;68(6):951-5. [Medline]
3. Huppke P, Gärtner J. Molecular diagnosis of Rett syndrome. J Child Neurol. 2005 Sep;20(9):732-6. [Medline]