How Do You Treat Adrenal Crisis?

Patient Presentation
A 3-year-old female with septo-optic dysplasia and panhypopituitarism was traveling on vacation. She had become acutely ill with emesis in the early hours of the morning. The emesis became more frequent so her parents brought her to the small community emergency room that was closest to their hotel. In the ER, she was alert and responsive but was mottled with a capillary refill of 4 seconds. Her respiratory rate was 38/minute, temperature of 37.8° and a blood pressure of 72/44. She had a mild dysconjugate gaze which was normal per her parents. Her heart and lungs were normal. She had slightly hyperactive bowel sounds and mildly diffuse abdominal pain and no organomegaly. She denied any suprapubic, costovertebral or McBurney’s point tenderness.

While an IV was established and fluids begun, her parents said that she had had been well and had taken all of her medications the day before. In retrospect her parents said that she probably had been drinking less the day before and seemed more tired, but they had attributed that to the traveling. She had been diagnosed early in life with septo-optic dysplasia and was treated by a multispecialty team at a children’s hospital. She had done relatively well and had not had any major crises so the family had decided to take a car trip across part of the country to visit relatives.

They had brought with them her emergency steroid medicine in case of adrenal crisis. The father said, “We know it’s supposed to be given in her leg muscle, but we’ve never done it and don’t want to do it.” The physician took the box along with an emergency treatment letter from the child’s doctor. He and the hospital pharmacist checked the emergency instructions and the IM hydrocortisone dosing. They calculated an appropriate IV dosing based on the emergency treatment letter and the pharmacist virtually ran back to the emergency room with the medication. In the meantime, the patient’s laboratory evaluation showed a sodium of 128 mEq/L, potassium of 4.4 mEq/L, and a glucose of 53 mg/dL. She also was now febrile and her blood pressure was not increasing. The physician ordered an additional .9 normal saline bolus along with piggyback fluids of D25W. At the same time, the physician was arranging a transfer to the regional children’s hospital. As the child appeared stable but getting sicker, an airflight ambulance was sent. While still in the ER, her blood pressure started to drop and pressor medications were begun which stablized her.

The physician found out a few weeks later that in the patient’s clinical course she had culture-negative sepsis that precipitated her adrenal crisis. She needed vasopressors for 48 hours but responded well to the antibiotics. She finished her course of antibiotics and was released with followup with her regular physicians.

Discussion
Septo-optic dysplasia (SOD) is a disorder of midline prosencephalic development early in gestation. It causes agenesis of the septum pellucidum and/or thinning or absence of the corpus callosum and pituitary hormone deficiencies. It has an incidence of 1:10,000 live births. Most cases appear to be due to a combination of genetic and environmental factors but there are rare familial cases which are most often autosomal recessive.

The phenotype is variable and diagnosis can occur at birth with more severe problems or later with milder ones. Patients must have at least 2 of 3 problems for diagnosis including uni- or bi-lateral optic nerve hypoplasia, midline brain defects (e.g. septum pellucidum absence or agenesis of the corpus callosum) and hypopituitarism (which is a hypothalamic hypopituitarism not a primary dysfunction of the gland itself). Patients have poor visual function, developmental delay, sleep problems, seizures and various endocrine deficiencies. The most common endocrinopathy is growth hormone deficiency, then thyroid stimulating hormone deficiency, then adrenocorticotropic hormone (ACTH) deficiency. The endocrinopathies do not have to be present at birth but can develop later. Patients with SOD are at risk for adrenal insufficiency (AI) as they obviously do not have the normal capacity to increase ACTH during stress.

The hypothamic-pituitary-adrenal axis is important for maintaining homeostasis in the metabolic and immune systems. Normally the hypothalamus secrets corticotrophin-release hormone (CRH) and argenine vasopressin (AVP). These stimulate the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH causes the adrenal gland to secrete aldosterone and cortisol along with androgenic steroids. Normally during stress, CRH, AVP and norepinephrine act to increase ACTH release. Cortisol, a glucocorticoid, maintains serum glucose. Aldosterone, a mineralocorticoid, maintains electrolyte balance and catecholamine balance for blood pressure modulation.

Learning Point
Adrenal insufficiency (AI) is defined as “…inadequate cellular corticoisteroid activity for the severity of the patient’s illness, [and] is the result of either a decrease in adrenal steroid production or tissue resistance to glucocorticoids.” In acute adrenal insufficiency or adrenal crisis, patients can have hypoglycemia, hyponatremia, hyperkalemia, hypotension, dehydration, altered mental status and thermodysregulation. Patients may also present with more nonspecific symptoms such as anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, and fever. It is a medical emergency requiring multispecialty treatment often in an intensive care setting in consultation with an endocrinologist.

  • For hypotension and dehydration, aggressive fluid resuscitation with isotonic saline with dextrose (usually D5 .9 normal saline) should be begun. Resuscitation must be carefully monitored to prevent water retention.
  • For hypoglycemia, additional dextrose (D25W) may be needed in addition to the dextrose in the other fluids.
  • Glucocorticoids can be given intravenously or intramuscularly. Intravenous is preferred as intramuscular injection may have a slower uptake because of decreased perfusion and dehydration.
    • Hydrocortisone (cortisol) is recommended because of its mineralocorticoid affect and should be given in stress doses – 50-75 mg/M2 x 1 dose initially, followed by 50-75 mg/M2 given daily divided into 4 doses.

    • Alternatives are methylprednisolone 10-15 mg/M2 and dexamethasone 1.5-2 mg/M2. Dexamethasone does not cross-react with hydrocortisone and so it can be used if AI is suspected and it will not confound confirmatory testing.

Careful monitoring of glucose, sodium, and potassium are needed. Other testing which can help includes cortisol, ACTH, aldosterone and renin levels. Underlying triggers of adrenal crisis need to be aggressively sought and treated.

Questions for Further Discussion
1. What disease processes cause adrenal insufficiency?
2. What triggers can cause adrenal crisis?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Adrenal Gland Disorders, Addison’s Disease and Pituitary Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Adrenal insufficiency: still a cause of morbidity and death in childhood. Shulman DI, Palmert MR, Kemp SF; Lawson Wilkins Drug and Therapeutics Committee. Pediatrics. 2007 Feb;119(2):e484-94.

The empty sella. Naing S, Frohman LA. Pediatr Endocrinol Rev. 2007 Jun;4(4):335-42.

Adrenal crisis provoked by dental infection: case report and review of the literature. Milenkovic A, Markovic D, Zdravkovic D, Peric T, Milenkovic T, Vukovic R. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Sep;110(3):325-9.

Septo-optic dysplasia. Fard MA, Wu-Chen WY, Man BL, Miller NR. Pediatr Endocrinol Rev. 2010 Sep;8(1):18-24.

Adrenal dysfunction in critically ill children. Karagüzel G, Cakir E. Minerva Endocrinol. 2014 Dec;39(4):235-43.

Author

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What is Jacquet Diaper Dermatitis?

Patient Presentation
A 13-month-old female came to clinic for a diaper rash of a few days that was not improving with usual treatments. The physical examination showed pink papular lesions that were slightly vesicular in the labial area with general erythema in the intertrigenous areas and satellite lesions. The patient was diagnosed with candidal diaper dermatitis and treated with nystatin. A second pediatrician saw her 3 weeks later the rash had not completely improved with the nystatin. The general erythema and satellite lesions had improved but she had flesh-colored papules that had central ulcerations. There was no umbilication and they were 4-5 mm in size mainly scattered around the labia major but with some that were more linear. There were some excoriations from the patient picking at them. The patient was diagnosed with impetigenous diaper dermatitis and given mupirocin as instructed to return to the clinic if not improving in the next few days. The pediatrician also considered that these were an underlying molluscum contagiosum or flat wart that had now been irritated and impetigenized. If not improving then a dermatology appointment would be made. Over the next month, the lesions had gone away with the mupirocin but then returned. The second doctor again saw the patient and the physical examination showed 4-5 mm flesh-colored papules that were flat on top with some central ulceration and no umbilication. They were scattered again. The physician was not sure what these lesions were and sent the patient to dermatology and restarted the mupirocin in the interim as it had appeared to help before.

The diagnosis of severe Jacquet’s erosive diaper dermatitis or granuloma glutate infantum was made by the dermatologist. As the patient had been using reusable diapers exclusively, it was recommended to use disposable diapers that were changed frequently. Additionally heavy use of zinc-based barrier cream was also recommended. Both pediatricians were surprised by the diagnosis and went to MEDLINE to learn more about it.

Discussion
The differential diagnosis of diaper dermatitis is usually fairly easy with irritant, fungal and bacterial causes being the most common. These are usually easily treated with resolution. When it is not improving then the differential must be expanded and other disease processes must be considered. These again usually include problems that are relatively easily treated such as scabies, lice or tinea. Other much less likely conditions in this age group would be syphilis or granuloma inguinale. Other signs or symptoms need to also be considered as Crohn’s disease, histocytosis or acrodermatitis enteropathica can present as a diaper rash also.

A review of rashes by distribution and pattern can be seen here.

Learning Point
Jacquet erosive diaper dermatitis (JED) is a severe irritant dermatitis that affects the genital area caused by prolonged moisture contact and fecal enzymes which alter the skin permeability and change the skin pH. These changes cause severe but non-specific inflammatory patterns. There are several patterns that have different names that are similar and some people believe they are all one disease process.

  • JED are 2-5 mm umbilicated or eroded papules and nodules which may be red-purple to begin with and have a heterogenerous pattern.

  • Perianal pseudoverrucous papules and nodules are papules and nodes that appear verrucous mainly in the perianal area but other areas as well..
  • Granuloma glutaela infantum is red-purpose nodules mainly the gluteal and groin areas that may have an eroded appearance.

Obviously it can be quite difficult to distinguish these entities. Additionally there are other names for these diseases in the literature including Sevestre and Jacquet erosive diaperdermatitis and dermatitis syphiloides posterosiva. Some believe that these entities are relatively rare because of the use of more absorbent disposable diapers but are reemerging because of a resurgence of using reusable diapers. These entities are also seen in the adult population with incontinence problems for a variety of reasons. Main treatment is changing to disposable diapers with frequent diapers changes. Additionally, other treatments including zinc-based creams, aqueous solution of eosin, anti-fungals, steroids, non-steroidal antiinflammatory drugs, and sucralfate have been used with varying success.

Questions for Further Discussion
1. What is your favorite diaper barrier cream and why?
2. What other treatments besides frequent diaper changes and barrier creams can be used to help diaper dermatitis?

Related Cases

    Symptom/Presentation: Rash

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Rashes and Common Infant and Newborn Problems.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Paradisi A, Capizzi R, Ghitti F, Lanza-Silveri S, Rendeli C, Guerriero C. Jacquet erosive diaper dermatitis: a therapeutic challenge.
Clin Exp Dermatol. 2009 Oct;34(7):e385-6.

Maruani A, Lorette G, Barbarot S, Potier A, Bessis D, Hasselmann C, Mazereeuw-Hautier J; Groupe de Recherche de la Societe Francaise de Dermatologie Pediatrique. Re-emergence of papulonodular napkin dermatitis with use of reusable diapers: report of 5 cases.
Eur J Dermatol. 2013 Apr 1;23(2):246-9.

Ricci F, Paradisi A, Perino F, Capizzi R, Paolucci V, Rendeli C, Guerriero C. Jacquet erosive diaper dermatitis: a not-so-rare syndrome. Eur J Dermatol. 2014 Mar-Apr;24(2):252-3.

Author

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Causes Bullae?

Patient Presentation
A 7-month-old male came to clinic with a severe diaper rash that had begun 2 days before. His mother said that it looked like a normal diaper rash and she was treating it with large amounts of zinc-based barrier creams but it was not improving. During the morning she had changed his diaper and thought that it was looking a beefier-red than before. About 1 hour later she changed him again and there were large fluid filled blisters on his buttocks cheeks. She was afraid she would break the blisters so she just took a picture with her cellphone, re-diapered him and called the clinic for an appointment. She denied using any other soaps/lotions/detergents. He was not taking any medicine except that she had given him some acetaminophen as his buttocks seemed painful. He was eating and drinking well and had not had a fever, diarrhea or emesis. The past medical history revealed general dry skin. The review of systems was otherwise normal.

The pertinent physical exam showed a well-appearing male with normal vital signs. His skin examination showed 4-5 cm open raw lesions centered on the buttock cheeks. There were no blisters but denuded skin could be seen. The area was generally bright red and there appeared to be some elevation of another area near the denuded skin on the right buttock. There were no satellite lesions and the intertrigenous areas were not affected. He had mildly reddened skin on his forearms and behind his knees but no blisters or crusting. The mother’s pictures looked like flaccid bullae. The laboratory evaluation of a culture of the area eventually grew Streptococcus. The diagnosis of bullous impetigo was made and the patient was started on cephalexin. Silvadene® cream was also prescribed and the patient had resolution within a few days.

Discussion
Bullae are fluid-filled epidermal lesions that are filled with serous or seropurulent fluid. They are > 1 cm in diameter and often easily rupture due to their thin walls. The differential diagnosis is different for bullae than for vesicular lesions with bullae being often more worrisome. However there is overlap and vesicular diseases can become large enough to be bullae. Drug toxicity and genetic problems are also more common in bullae whereas vesicles are more often caused by infectious diseases.

Potentially life threatening conditions such as toxic epidermal necrolysis syndrome, Stevens Johnson syndrome or meningococcemia need to be recognized and treated aggressively. Symptoms may include skin sloughing, petechiae or purpura, fever and irritability, inflammation of the mucosa, urticaria, respiratory distress, and diarrhea or abdominal pain. As bullae can cover extensive amounts of the skin and are often fragile, they may need specialized skin treatment with dermatology and burn specialists. Other supportive treatments such as fluid management, antibiotics and even respiratory support may be needed.

Vesicles are circumscribed, elevated, fluid-filled lesions < 1 cm in diameters on the skin. They contain serous exudates or a mixture of blood and serum. They last for a short time and either break spontaneously or evolve into bullae. They can be discrete (e.g. varicella or rickettsial disease), grouped (e.g. herpes), linear (e.g. rhus dermatitis) or irregular (e.g. coxsackie) in distribution.

A review and differential diagnosis of vesicles can be found here. Information about streptococcal diseases can be found here.

Learning Point

The differential diagnosis of bullae includes:

  • Trauma
    • Burns – including sunburn
    • Frostbite
    • Stings
  • Infection
    • Impetigo and Staphylococcal scalded skin syndrome
    • Herpes
    • Meningococcemia
    • Orf
    • Syphilis
  • Genetic
    • Acrodermatitis enteropathica
    • Epidermolysis bullosa
    • Incontinentia pigmenti
    • Porphyria
  • Other
    • Bullous disease of childhood
    • Drugs
    • Lupus erythematosis
    • Toxic epidermal necrolysis syndrome (TEN syndrome)
    • Pemphigus
    • Stevens Johnson syndrome

Questions for Further Discussion
1. What other disease entities are caused by Streptococcus?
2. What causes Stevens Johnson syndrome?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Streptococcal Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications: Oxford. 1988:361-3.

Barr K. Evaluation of vesicular-bullous rash. ePocrates.
Available from the Internet at https://online.epocrates.com/u/2911775/Evaluation+of+vesicular-bullous+rash/Differential/Overview (rev.10/3/2014, cited 3/16/2015).

Author

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

How Long Do Creatine Kinase Levels Remain Elevated After Exercise?

Patient Presentation
A 15-year-old male came to clinic in the morning for his health supervision visit. He was a basketball player and runner and was at the end of the basketball season and would be starting track soon. He had had no specific injuries and was doing well in school. The past medical history showed no athletic injuries, fainting, passing out, or palpitations. The family history was negative for neurological and rheumatologic problems. The review of systems was negative.

The pertinent physical exam showed a thin adolescent male with normal vital signs and mild comedomal acne. His musculoskeletal exam had normal strength and tone, and his neurological examination was also normal. The diagnosis of a healthy male was made. The patient went to the laboratory to have routine screening laboratories done including a hemoglobin/hematocrit and lipids. The laboratory evaluation was all normal, but a creatine kinase (CK) had been done inadvertently and was elevated at 420 U/L (normal 60-400 U/L). The physician called the patient that afternoon who confirmed that he wasn’t having any muscle pain, and had been drinking well during the evening before and at breakfast before the lab testing earlier. He also confirmed a normal basketball practice last evening and denied any trauma. The pediatrician felt that this was most consistent with CK elevation due to exercise, but wasn’t sure how long it took for CKs become normal after exercise. Repeat testing 2 weeks later during a break between athletic seasons showed a CK of 148 U/L on a morning blood sample.

Discussion
Acute rhabdomyolysis is an emergency that can cause acute renal failure (especially acute tubular necrosis caused by myoglobinemia) and electrolyte abnormalities. Common presenting findings are dark urine, myalgia and muscle weakness. Milder episodes can go unnoticed. Acute exertional rhabdomyolysis or unrecognized muscle injury can occur in underconditioned persons and even trained athletes who increase their exertion or exercise. Being unaccustomed to the ambient conditions such as heat, humidity and sun can also increase fluid loss and the risk of muscle injury. An overview and differential diagnosis of rhabdomyolysis can be found here.

Learning Point
Laboratory testing for rhabdomyolysis includes CK which is often used as a marker for myoglobinemia. CK remains elevated for relatively long periods of time and has slower elimination characteristics than myoglobin. Some data from military recruits and athletes has shown that CK and myoglobin increase especially at the beginning of an exercise programs but also remains elevated with ongoing exercise. Therefore, it is reasonable to conclude that this patient’s CK elevation was due to his exercise.

CK caused by rhabdomyolysis usually rises within 12 hours, peaks at 24-36 hours and then decreases 35-40% per day. Therefore levels that are not decreasing after the appropriate time indicate continued insult.

Questions for Further Discussion
1. What causes hematuria?
2. What causes proteinuria?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Muscle Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Melamed I, Romem Y, Keren G, Epstein Y, Dolev E. March myoglobinemia: a hazard to renal function. Arch Intern Med. 1982 Jul;142(7):1277-9.

Thomas BD Jr, Motley CP. Myoglobinemia and endurance exercise: a study of twenty-five participants in a triathlon competition. Am J Sports Med. 1984 Mar-Apr;12(2):113-9.

Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2011. MSMR. 2012 Mar;19(3):17-9.

Lappalainen H, Tiula E, Uotila L, Manttari M. Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up. Crit Care Med. 2002 Oct;30(10):2212-5.

Quinlivan R, Jungbluth H. Myopathic causes of exercise intolerance with rhabdomyolysis. Dev Med Child Neurol. 2012 Oct;54(10):886-91.

Muscal E. Rhabdomyolysis Workup. eMedicine.
Available from the Internet at http://emedicine.medscape.com/article/1007814-workup#aw2aab6b5b2 (rev. 4/24/14, cited 3/10/15).

Author

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital