Croup overview

# Overview
Croup is an upper respiratory disease entailing swelling of the trachea caused by infection from human parainfluenza virus - an enveloped, single stranded negative sense RNA virus with four distinct serotypes. Development of viral croup results from infiltration of histiocytes, lymphocytes, plasma cells, and neutrophils white blood cells primarily by human parainfluenza viruses (HPIV). The infiltration from HPIV causes inflammation by the up-regulated production of cytokines, localized in the trachea. HPIV-response Immunoglobulin E (IgE) release inhibits histamine, contributing to the inflammation of the trachea and leading to swelling of the larynx, trachea, and large bronchi that obstructs the airways, leading to croup. Known as "barking cough", croup manifests through symptoms including a "bark-like" cough, stridor, hoarseness, respiratory distress, and common cold symptoms such as runny nose and low-grade fever. Croup symptoms typically manifest after 2-7 days of human parainfluenza virus infection, usually lasting between 24-48 hours with only rare instances reported of up to 7 days. They will typically resolve without treatment, excepting the most severe cases that pose the threat of respiratory failure. Croup must be differentiated from other upper respiratory diseases and conditions that cause airway obstruction around the larynx, as well as those that present similar symptoms to influenza.  Croup is a very common disease and is almost always found in children between 6 months and 6 years of age, but rare cases have been reported in children as young as 3 months and as old as 15 years. Primary measures of preventing croup involve preventing the spread of human parainfluenza virus. This is accomplished by maintaining personal hygiene, such as washing hands frequently, and limiting exposure to patients with croup or other respiratory illness. Medical therapies to treat croup are dependent on the classification of the particular case: mild, moderate, severe, and imminent respiratory failure. For mild croup, glucocorticoid therapy is usually sufficient to alleviate symptoms, typically administering nebulized dexmethasone and budesonide. For more severe cases, nebulized racemic and L-epinephrine is administered in conjunction with glucocorticoids. Hospitalization and intubation is very rare and is usually only used when the respiratory distress is life-threatening. Common physical examination findings of croup are primarily chest and lung abnormalities. This includes inspiratory stridor, expiratory wheezing, suprasternal and intercostal indrawing, sternal wall retractions, and desynchronized chest and abdominal wall expansion. Low-grade fever can be present, as well as cyanosis in severe cases. Diagnosis of croup is dependent on x-ray imaging of the chest and neck, with diagnostic images indicative of croup including evidence of steeple sign: narrowing of the subglottic lumen in the neck. It also includes a visibly distended hypopharynx in some cases. Prognosis of croup is usually good, with mild and moderate croup usually resolving itself without treatment. Severe cases of croup can have poor prognosis, if untreated, due to the possibility of respiratory failure. All classifications of croup have good prognosis with appropriate treatment.

# Historical Perspective
Diptheritic croup reports date back to the Homer-era of Ancient Greece, speculating to have emerged in the 12th century B.C.E. The Viral-based croup was discovered in 1826 by French medical doctor Pierre Bretonneau. Initial therapies included cold water mist to soothe pain as well as tracheotomy for patients with severe cases requiring hospitalization. In the 1970s, nebulized Epinephrine emerged as a therapy. Glucocorticoid therapies emerged in the late 1980s' and 1990's. Preventative therapy emerged with successful immunization of individuals against diptheritic croup with the development of influenza and diptheria vaccines.

# Pathophysiology
Development of croup results from infiltration of white blood cells through the human parainfluenza virus (HPIV). HPIV expels its nucleocapsid into the recipient cell cytoplasm. The viral transcription then occurs through the HPIV RNA-dependent RNA polymerase. The viral mRNAs are translated into viral proteins, leading to the replication of the genome into the negative-sense RNA strand, which is then encapsidated by the nucleoprotein and used for further transcription and replication. The inflammation response to HPIV occurs from the up-regulation of cytokines and the released Immunoglobulin E inhibiting histamine. The resultant swelling of the larynx, trachea, and large bronchi obstructs the airways, which leads to croup.

# Causes
Human parainfluenza virus is an enveloped, single stranded negative sense RNA virus with four distinct serotypes. The virus genome consists of approximately 15,000 nucleotides used to encode six structural proteins; they function to attach, enter, and fuse with the host cell, forming a complex with the RNA genome. Human parainfluenza virus is a member of the paramyxoviridae family. It is a member of one of two genuses depending on the serotype: Respirovirus or rubulavirus. Human parainfluenza virus infects the body by infiltrating white blood cells. It is transmitted through respiratory droplets through the air, as well as physical contact with an infected individual or contaminated physical surface.

# Classification
Croup is classified by severity of symptoms. The Westley Score system quantifies symptoms from a score of 0-5. The sum of the symptom score stratifies croup into mild, moderate, severe, or indicative of total respiratory failure.

# Differentiating Croup from Other Diseases
Croup must be differentiated from other upper respiratory diseases and conditions that cause upper airway obstruction around the larynx, as well as those that present similar symptoms to influenza.

# Epidemiology and Demographics
Annually, the incidence of croup is approximately 532/100,000 individuals, peaking in the fall of each year. Croup is primarily found in children between 6 months and 6 years of age, but rare cases have been reported in children as young as 3 months and as old as 15 years. Males are 1.5 times more likely to develop croup.

# Risk Factors
Risk factors for croup include being male and between 6 months and 6 years old, family history of the disease, living in a densely populated region, traveling to or from developing countries, and lacking an influenza vaccine.

# Natural History, Complications and Prognosis
Croup symptoms typically manifest after 2-7 days of human parainfluenza virus infection. Symptoms will typically last between 24-48 hours; very rarely they will last up to 7 days. They will typically resolve without treatment, excepting the most severe cases that pose the threat of respiratory failure. Prognosis is good in mild and moderate croup with and without treatment. Severe croup and impending respiratory failure classifications have poor prognosis, if left untreated, due to life-threatening airway obstruction. With treatment, all manifestations of croup have a good prognosis. Complications of croup stem from airway obstruction, including respiratory failure and respiratory distress. They also stem from infections due to immunocompromise from the causative human parainfluenza virus and corticosteroid therapy; these include bacterial tracheitis, atelectasis, pneumonia, pulmonary edema, and epiglottitis.

# Diagnosis

## History and Symptoms
Symptoms of croup include: barking cough, stridor, hoarseness, difficulty breathing, and common cold symptoms. Family history of history of croup in the patient can help determine and differentiate a croup diagnosis.

## Physical Examination
Common physical examination findings of croup are primarily chest and lung abnormalities. This includes inspiratory stridor, expiratory wheezing, suprasternal and intercostal indrawing, sternal wall retractions, and desynchronized chest and abdominal wall expansion. Additionally, croup patients often appear ill, similarly to common cold patients, and lethargic. Low-grade fever can be present, as well as cyanosis in severe cases.

## Laboratory Findings
Laboratory findings may include abnormal white blood cell counts as well as markers for inflammation.

## X Ray
X Ray findings in croup patients include evidence of steeple sign: narrowing of the subglottic lumen in the neck. It also includes a visibly distended hypopharynx in some cases.

## Other Diagnostic Studies
Croup's exact cause can be determined by a nasopharyngeal swab. It is not usually performed since it is not usually necessary for diagnosis, as well as presenting patient distress and having no impact on management and treatment.

# Treatment

## Medical Therapy
The primary medical therapy used to treat croup depends on the severity of the case. For mild croup, glucocorticoid therapy is primarily used to alleviate symptoms by reducing tracheal swelling and inflammation. The main corticosteroids used are dexamethasone and/or budesonide, administered orally or, rarely, via a parenteral method. These are usually effective beginning 6 hours post-treatment. For moderate and severe croup, epinephrine is used in conjunction with glucocorticoids. The primary epinephrine therapies used are racemic epinephrine or L-epinephrine, both in nebulized form. Epinephrine alleviates symptoms within 10-30 minutes, but they usually return within 2 hours, requiring repeated dosing for long-term relief. Hospitalization is rarely required and is primarily used for observation and symptom management in children. Intubation is a rare necessary treatment for hospitalized children with the most severe croup cases.

## Prevention
Primary measures of preventing croup involve maintaining personal hygiene, such as washing hands frequently, and limiting exposure to patients with croup or other respiratory illness. Prevention for rarer causes of croup include vaccinations for haemophilus influenzae (Hib), measles, and diptheria.