and mortality, necessitating rapid diagnosis and treatment.
The SCARs (severe cutaneous adverse reactions) encompass a group of T‐cell mediated, type IV hypersensitivity reactions which are often stimulated by medications or their metabolites. SCARs include Stevens‐Johnson syndrome (SJS), toxic‐epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), and SJS/TENs overlap.
SJS and TEN are now recognised as two points on the spectrum of the same pathologic process. SJS and TEN are rare SCARs which are characterised by significant epidermal and mucosal loss. Typically, SJS/TEN will occur 7–10 days after initiation a culprit drug, and classically starts on the face and trunk and rapidly spreads over a few days – lesions can be macular or targetoid and desquamate over time. Nikolsky’s sign, where rubbed skin leads to exfoliation of the outermost layer, is typically positive, and mucosal surfaces are often involved. Classification is by percentage of body area involved; less than 10% is SJS, between 10 and 30% is SJS/TEN overlap, and greater than 30% is TEN. Acute respiratory distress, bacteraemia, and other infections are common complications, and mortality is high. Treatment is by ceasing the offending drug, aggressive supportive care, and sometimes IVIG.
DRESS is characterised by a widespread rash – most typically a maculopapular morbilliform exanthem, i.e. the rash looks like measles – fever and visceral organ involvement. Hypereosinophilia is common as is facial oedema and lymphadenopathy – mucosa is spared. The rash usually develops greater than three weeks after starting a medication and persists after cessation. Cessation of the drug, supportive measures and prednisolone are the usual treatments. Fatality is lower than with SJS/TEN but approaches 10%.
AGEP has the lowest mortality of the SCARs, with some modern case series showing no fatalities. However, this drug rash is still striking, with widespread or skin fold erythema evolving to innumerable pinhead‐sized sterile pustules, and typically resolving within two weeks of drug cessation. AGEP is thought to be mediated through T‐cell activation of neutrophils. Spider bites have been thought to cause AGEP, and the rash shares similarities with pustular psoriasis, but with a more acute onset. Major morbidity and occasional mortality can usually be attributed to bacterial superinfection of the lesions.
Dermatological emergencies can also be caused by, or be indicative of, severe infection. Staphylococcal scalded skin syndrome (SSSS) is a highly feared complication of infection with Staphylococcus aureus secreting exfoliative toxin. Most commonly experienced by children, where fatality rates are lower, SSSS has high mortality rates in adults, of around 50%. Erythematous areas in SSSS typically develop around the face, neck, axilla, and perineum, and progress to flaccid bullae, mucous membranes are typically spared. Nikolsky’s sign is positive. Treatment is with antibiotics and supportive care, usually involving intravenous fluids and nasogastric feeding.
Meningococcal septicaemia is characterised by rash, which is typically maculo‐papular and blanching when seen very early in the disease course, and remains blanching in 10 to 15% of cases, and 5 to 10% of patients do not develop rash. However, around 70% of patients have the typical, non‐blanching rash, which is either petechial or purpuric, on presentation to hospital. Given the severe nature of invasive meningococcal disease, other symptoms and signs need to be taken into account in presumptive diagnosis – the rash is not sensitive enough.
Necrotising fasciitis is a severe subcutaneous infection that requires surgical debridement in addition to antibiotics. Early diagnosis has positive impact on outcome, and typically, early infection resembles severe cellulitis except for severe tenderness, severe sepsis, and rapidly progressive rash, signs which should prompt a high index of suspicion for the disease. Type I necrotising fasciitis is typically polymicrobial with both aerobic and anaerobic bacteria, whereas type II is monomicrobial, and usually caused by Group A Streptococcus.
Disseminated candidiasis with skin lesions is a rare complication of profound immune suppression, most commonly neutropaenic patients with acute myeloid leukaemia during induction therapy. Diffuse maculopapular lesions predominate in cases caused by Candida tropicalis, and nodular or papular lesions in cases caused by Candida krusei.
Vashi N. The Dermatology Handbook. Cham: Springer International Publishing; 2019.
https://link.springer.com/chapter/10.1007/978-3-030-15157-7_5
4 Endocrinology
Questions
Answers can be found in the Endocrinology Answers section at the end of this chapter.
1 1. A 48‐year‐old woman is referred by her GP with a 3‐month history of headaches and night sweats for investigation. Her medical history includes difficult to control hypertension for 5 years which requires 3 agents; OSA on CPAP treatment, glucose intolerance, and total hysterectomy 7 years ago. On examination, BP is 156/95 mmHg, her hands are large, and she is no longer able to wear her ring. There is no hirsutism buts there is coarseness of her facial features. Her laboratory test results and MRI of head are shown below.TestsResultsNormal valuesHbA1c6.5%<6.0%Cortisol (9 am)320 nmol/L133–540Free T415 pmol/L10–20Prolactin278 mIU/L90–630Estradiol48 pg/ml15–350Growth hormone (GH)362 pmol/L<226Insulin like growth factor 1 (IGF‐1)748 ng/ml<320What is the most appropriate next step for this patient? Inferior petrosal sinus sampling for growth hormone.Measurement of growth hormone after insulin induced hypoglycaemia.Measurement of growth hormone releasing hormone (GHRH).Referral to neurosurgery.
2 2. A 28‐year‐old woman presents to the emergency department with symptoms of nausea, vomiting, diarrhoea, severe lethargy, weakness, and drowsiness. Her BP is 85/45 mmHg, heart rate is 98 bpm, respiratory rate is 13/min, blood glucose level is 5.6 mmol/L [3.2–5.5 fasting], and temperature is 38°C. Her serum sodium level is 130 mmol/L [135–145] and potassium level is 5.8 mmol/L [3.5–5.2]. You find a MedicAlert necklace which says, ‘Adrenal insufficiency’.Which one of the following steps of management is INCORRECT?Administer IV hydrocortisone 100 mg stat followed by IV hydrocortisone 50 mg qid.Administer IV 0.9% normal saline 1 L within the first hour.Avoid giving corticosteroid due to the potential risks of worsening sepsis.Perform a septic screen and start empirical broad‐spectrum antibiotics.
3 3. A 65‐year‐old woman was referred by her GP to the general medicine clinic with a 2.5 cm adrenal mass during investigation for abdominal discomfort. She reports no symptoms of headache, sweating, palpitations, significant weight changes, night sweats, fever, nausea, vomiting or proximal muscle weakness. She has a history of hypertension, type 2 diabetes, obesity, and osteoporosis.Which one of the following investigations is NOT indicated at this stage?24‐hr urinary fractionated metanephrine and catecholamine collection.Overnight dexamethasone (1 mg) suppression test.Plasma aldosterone and plasma renin activity measurement.Positron‐emission tomography (PET) scan.
4 4. A 65‐year‐old man is referred to the endocrine clinic with a 6‐week history of unintentional weight loss (5 kg), diarrhoea, myopathy and lethargy. He has a history of atrial fibrillation, diagnosed one year previously. He was started on amiodarone and warfarin but he reverted to sinus rhythm spontaneously at which point the amiodarone was stopped 6 months prior to presentation. On examination, there is no obvious goitre. He has an irregularly irregular pulse at 90 bpm. His skin is warm and sweaty. His TSH level is 0.2 mIU/L [0.4–4.0], Free T4 level 30 pmol/L [9.0–25.0], and Free T3 10–pmol/L [3.5–7.8].Which one of the following management strategies is correct?Commence carbimazole.Commence high‐dose oral prednisolone.Commence carbimazole and high‐dose oral prednisolone.Referral for thyroidectomy.
5 5.
