Читать книгу How to Pass the FRACP Written Examination - Jonathan Gleadle - Страница 21

1. Answer: C

Bullous pemphigoid is a rare autoimmune skin condition with an increasing incidence over the last two decades. It is caused by autoantibody‐mediated damage to the epithelial basement membrane of the epidermis. IgG +/‐ IgE antibody and activated T cells attack the protein BP180 (Type XVII collagen), or less frequently BP230 (a plakin), in the basement membrane.

There are HLA associations to suggest genetic predisposition to the disease. It most commonly affects elderly patients over the age of 70. However, drug‐induced bullous pemphigoid is linked to patients who are younger than 70 years of age and has a male predominance. The risk of developing bullous pemphigoid is greater in elderly patients with neurological disease, such as stroke, dementia, Parkinson’s disease, unipolar disorder, bipolar disease, and multiple sclerosis. The risk of developing bullous pemphigoid is also increased in patients with psoriasis and in patients treated with phototherapy. A medication, trauma, or skin infection can trigger the onset of bullous pemphigoid. Medications which are associated with bullous pemphigoid include penicillamine, frusemide, spironolactone, captopril, penicillin and its derivative, sulfasalazine, salicylazosulfapyridine, phenacetin, nalidixic acid, topical fluorouracil, neuroleptics, and dipeptidyl‐peptidase 4 (DPP‐4) inhibitors. Bullous pemphigoid is associated with underlying malignancy and appropriate screening is important.

Schmidt E, Zillikens D. Pemphigoid diseases. The Lancet. 2013;381(9863):320–332.

https://www.ncbi.nlm.nih.gov/pubmed/23237497

2. Answer: C

This patient is likely to have coeliac disease. Classically, patients with coeliac disease present with steatorrhea, weight loss, nutrient deficiency, and resolution of the mucosal lesions (villous atrophy) and symptoms upon withdrawal of gluten‐containing foods. The malabsorption may cause weight loss, severe anaemia, neurologic disorders from deficiencies of B vitamins, and osteopenia from deficiency of vitamin D and calcium. Coeliac disease can exist in a very mild form and go largely undetected.

Dermatitis herpetiformis (DH) is a rare but persistent immunobullous disease associated with coeliac disease. It develops in 15 to 25% of patients with coeliac disease. There is a genetic predisposition with an association with HLA, DQ2, and DQ8. Some patients have a personal or family history of other autoimmune diseases including thyroid disease, pernicious anaemia, type 1 diabetes, vitiligo, and Addison disease.

DH is characterised by its intense pruritus. Because of severe itching, intact vesicles are rarely seen. DH has a symmetrical distribution. The location of the lesions aids in the diagnosis. Lesions are most commonly seen on the extensor surfaces of knees, elbows and on buttocks. Lesions are seldom seen on the face, neck, scalp, palms, or soles.

DH diagnosis is based on typical clinical picture and demonstration of IgA deposition in papillary dermis. DH usually has a good prognosis, with the majority of patients responding well to a strict gluten‐free diet and medication.

Salmi T. Dermatitis herpetiformis. Clinical and Experimental Dermatology. 2019;44(7):728–731.

https://onlinelibrary.wiley.com/doi/full/10.1111/ced.13992

3. Answer: A

This patient has erythema nodosum which is likely secondary to previously undiagnosed Crohn’s disease which can be hypothesised from her history of mouth ulcers, abdominal pain, diarrhoea, and microcytic anaemia. Her serum calcium level is normal and CXR is normal which does not suggest sarcoidosis. There is also no lymphadenopathy or hepatosplenomegaly to suggest lymphoma.

Erythema nodosum is the most common type of panniculitis. Generally, it is idiopathic in 50% of cases, however there are many possible causes (Table 3.1). Erythema nodosum often occurs in association with granulomatous disease including sarcoidosis, tuberculosis, and granulomatous colitis. The hallmark of erythema nodosum is painful, tender, erythematous, subcutaneous nodules that typically are located symmetrically on the anterior surface of the lower extremities and is a nonspecific cutaneous reaction pattern to a variety of antigens.

Table 3.1 Common causes of erythema nodosum.

Infection

Streptococcal pharyngitisMycoplasmaTuberculosisSyphilisViral infection: HSV, EBV, hepatitis B and C, HIV

Inflammatory bowel disease

Ulcerative colitisCrohn’s disease

Sarcoidosis

Drugs

Antibiotics: sulfonamides, amoxicillin; oral contraceptives

Lymphoma and other malignancies

Evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens. Erythema nodosum represents an inflammatory process involving the septa between subcutaneous fat lobules, with an absence of vasculitis and the presence of radial granulomas. These nodules tend to be self‐limiting; they do not ulcerate and usually resolve without atrophy or scarring. Pain can be managed with NSAIDs and prednisolone (1 mg/kg) may be used until the erythema nodosum resolves if underlying infection has been excluded. However most importantly, any underlying causes should be treated.

Chowaniec M, Starba A, Wiland P. Erythema nodosum – review of the literature. Reumatologia/Rheumatology. 2016;2:79–82.

https://www.termedia.pl/Erythema-nodosum-review-of-the-literature,18,27671,1,1.html

4. Answer: A

The combination of palpable purpura, arthritis/arthralgia, abdominal pain. and haematuria in a young person is highly suggestive of Henoch‐Schonlein (HSP) or IgA vasculitis. HSP is an immune‐mediated vasculitis associated with IgA deposition. Skin biopsy shows leukocytoclastic vasculitis with IgA staining of superficial dermal vessels. Some degree of renal involvement is seen in 35 to 54% of adult patients. Renal biopsy primarily shows IgA deposition in the mesangium in both HSP and IgA nephropathy suggesting similar pathogenesis.

The majority of HSP cases are preceded by an upper respiratory tract infection suggesting a potential infectious trigger. Streptococcus, staphylococcus, and parainfluenza are the most commonly implicated pathogens.

Diagnosis of HSP is based on the presence of purpura (palpable) or petechiae (without thrombocytopaenia) with lower limb predominance (mandatory criterion) plus at least one of the following four features: (i) abdominal pain, (ii) arthritis or arthralgia, (iii) leukocytoclastic vasculitis or proliferative glomerulonephritis with predominant deposition of IgA on histology, (iv) renal involvement (haematuria, red blood cell casts, proteinuria). Laboratory tests focus on assessing renal involvement (urinalysis, urine microscopy, proteinuria, serum creatinine).

There are no blood tests specific for HSP. Although the IgA system plays a central role in the pathophysiology, measurement of serum levels of total IgA is not helpful in confirming the diagnosis or providing prognostic information. Galactose‐deficient IgA1 serum levels seem to distinguish patients with HSP nephritis from patients without nephritis.

Gastrointestinal involvement is relatively common with typical colicky abdominal pain. In a recent case series, main clinical manifestations were abdominal pain (100%), nausea and vomiting (14.4%), melaena and/or rectorrhagia (12.9%), and positive FOBT (10.3%). Symptoms are caused by bowel ischemia and oedema. Serious complications include infarction and perforation. Descending duodenum and the terminal ileum are frequently involved, with endoscopic features including diffuse mucosal redness, petechiae, haemorrhagic erosions, and ulcers. CT scan features are commonly bowel wall thickening with engorgement of mesenteric vessels.

Patients with HSP usually do not have thrombocytopenia. It is extremely rare that patients with HSP also have positive ANCA and MPO. If present, patient usually have severe and rapid progressive renal failure. It has been suggested these patients should be treated with high dose steroid and cyclophosphamide.

Management of HSP includes supportive care, symptomatic therapy and, in some cases, immunosuppressive treatment. Immunosuppressive treatment of HSP nephritis is used in patients with severe kidney involvement (nephrotic range proteinuria and/or progressive renal impairment). In these cases, renal biopsy should be considered before treatment. Mild renal involvement (microscopic haematuria or mild proteinuria) does not require biopsy or immunosuppressive treatment.

In patients with rapidly progressive glomerulonephritis or nephrotic syndrome (usually accompanied by crescents on kidney biopsy), pulsed intravenous methylprednisolone followed by 3‐ to 6‐month course of oral steroids is most commonly used. A current KDIGO guideline suggests adding cyclophosphamide to steroid treatment for crescentic IgA glomerulonephritis.

Audemard‐Verger A, Pillebout E, Guillevin L, Thervet E, Terrier B. IgA vasculitis (Henoch–Shönlein purpura) in adults: Diagnostic and therapeutic aspects. Autoimmunity Reviews. 2015;14(7):579–585.

https://www.sciencedirect.com/science/article/abs/pii/S1568997215000361?via%3Dihub

5. Answer: A

The malignant transformation of melanocytes into melanoma is due to a complex interaction between exogenous and endogenous triggers as well as tumour‐intrinsic and immune‐related factors. Cutaneous melanomas carry a particularly high mutational load and harbour a high number of ultraviolet‐signature mutations, such as C→T (caused by ultraviolet B) or G→T (caused by ultraviolet A) transitions. Although many pathogenetically relevant mutations in melanoma are assumed to originate from a direct mutagenic effect of ultraviolet B and A, indirect effects such as the production of free radicals resulting from the biochemical interaction of ultraviolet A with melanin also cause mutations and genetic aberrations.

Melanoma is a molecularly heterogenous malignancy. Malignant transformation into melanoma follows a sequential genetic model that results in constitutive activation of oncogenic signal transduction. Systematic genome‐wide screening has identified missense mutations in BRAF, a component of the mitogen activated protein kinase (MAPK) pathway in 66% of melanomas. BRAFv600 mutation is a typical feature of benign naevus formation. Further progression into intermediate lesions and melanomas in situ requires additional mutations – for example, mutations in the telomerase reverse‐transcriptase (TERT) promoter. To gain invasive potential, tertiary mutations in cell‐cycle controlling genes (cyclin‐dependent kinase‐inhibitor 2A [CDKN2A]) or chromatin‐remodelling (AT‐rich interaction domain [ARID]1A, ARID1B, ARID2) are required. Metastatic melanoma progression is associated with mutations in phosphatase‐ and‐tensin homologue (PTEN) or tumour‐protein p53 (TP53).

BRAF inhibitors such as dabrafenib and trametinib are standards of care in patients with stage‐3 BRAF mutated melanoma. Several randomised phase 3 clinical trials have shown objective response rates to BRAF inhibitors of approximately 50%, which can be increased to 70% when combined with MEK inhibitors.

Schadendorf D, van Akkooi A, Berking C, Griewank K, Gutzmer R, Hauschild A et al. Melanoma. The Lancet. 2018;392(10151):971–984.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31559-9/fulltext

6. Answer: B

This patient has melanoma in the context of diabetic neuropathy which may have impact on the wound healing. However, the Breslow thickness is 4 mm and she will require a wider local excision with margins of 2 cm. The guidelines for surgical margins of melanomas can be seen in the table below.

Sentinel lymph node biopsy (SLNB) is a surgical technique to identify low volume metastatic disease within the draining lymph node basin in patients undergoing treatment for primary melanoma. SLNB is a staging procedure to identify patients with a positive draining nodal basin and thereby minimise the morbidity associated with elective lymph node dissection in patients who may not require this procedure. Moreover, it provides prognostic stratification. Numerous studies have consistently demonstrated that the status of the sentinel lymph node (SLN) reflects the status of the entire draining nodal basin as measured by elective lymph node dissection. The recently revised American Joint Committee on Cancer (AJCC) staging system (8th edition) requires a SLNB for patients with primary melanoma >1 mm in thickness and for some patients with thin melanomas but with high risk factors in order to perform microstaging of the lymph node basin and accurately allocate a pathological disease stage.

SLNB involves pre‐operative lymphoscintigraphy to identify the draining nodal basin for the anatomical location of the primary melanoma. This is followed by intraoperative intradermal injection of the melanoma site with patent blue dye. Intraoperative exploration through a small incision allows the identification of SLNs. A node is considered a SLN if it has tracer uptake and/or is stained blue. This dual modality approach allows the successful identification of a SLN in over 95% of patients. SLNs are carefully examined pathologically to identify metastasis.

Breslow thickness	Surgical margin for excision
Melanoma in situ	5 mm
Melanoma <1 mm	1 cm
Melanoma 1–2 mm	1–2 cm
Melanoma 2–4 mm	1–2 cm
Melanoma >4 mm	2 cm

Gyorki D, Barbour A, Mar V, Sandhu S, Hanikeri M. When is a sentinel node biopsy indicated? – Clinical Guidelines Wiki [Internet]. Cancer Council Australia: Clinical Guideline Network. 2020 [cited 15 February 2020]. Available from:

https://wiki.cancer.org.au/australia/Clinical_question:When_is_a_sentinel_node_biopsy_indicated%3F

7. Answer: D

Porphyria is a predominantly inherited metabolic disorder resulting from a deficiency of an enzyme in the heme production pathway and overproduction of toxic heme precursors. There are three principal types of porphyria: porphyria cutanea tarda, (PCT), acute intermittent porphyria, and protoporphyria.

This patient’s clinical picture is consistent with PCT: the most common porphyria affecting 5–10 persons per 100 000 people. The cause is inhibition of the fifth enzyme in heme biosynthetic pathway: uroporphyrinogen decarboxylase. PCT is associated with several precipitating factors such as haemochromatosis (53%) and uroporphyrinogen decarboxylase mutations (17%), as well as hepatitis C (69%), alcohol (8%), tobacco (81%), oestrogen (6%), and HIV (15%). Typically, patients are >40 year old and male. The clinical picture is of painless blistering lesions in sun exposed areas, typically the back of the hands. Sun exposed skin can be friable, scarred, or develop hypertrichosis. Remission may occur in the winter months, if sunlight exposure is decreased. Urine is brown–reddish, due to excess uroporphyrin. PCT is usually associated with mild abnormal LFTs. Advanced liver disease is uncommon at initial presentation but may be seen in older patients with recurrent disease. Diagnosis is made with an elevated urine or plasma porphyrin with predominantly uroporphyrin and heptacarboxyporphyrin. Erythrocyte porphyrins are usually normal. A total plasma porphyrin measurement may be most useful for initial screening. A skin biopsy reveals subepidermal bullae. Wood’s lamp examination of the urine shows orange red fluorescence.

First line treatment for PCT involves addressing modifiable risk factors: treating hepatitis C or HIV if present, and restricting alcohol, tobacco, and oestrogen. These factors, in combination with hepatic iron depletion via phlebotomy or iron chelation to a target ferritin at the low end of the normal range, often produces remission. Hydroxychloroquine is an alternative to iron depletion. Once in remission, patients may relapse, especially if they drink >4 standard drinks/ day or continue smoking, so urine or plasma uroporphyrin should be measured annually.

Acute intermittent porphyria is an autosomal dominant partial deficiency of the third enzyme of heme synthesis: porphobilinogen deaminase (or hydroxymehtlbilane synthase). 90% of patients are females, typically presenting aged 18–45 with a prodrome of days of severe fatigue and lack of concentration, then worsening abdominal pain, nausea, vomiting, afebrile tachycardia, and neurological signs including weakness dysthesia, and seizures (20% of patients). Risk factors include cytochrome P450 inducers, oral contraceptive pill, and severely restricted caloric intake. Abdominal exam is often unremarkable and blood tests usually show mild liver derangement and hyponatremia. Diagnosis requires elevated porphobilinogen in urine and plasma, often up to 10–150x normal. Urine colour can be unremarkable, however if exposed to light can turn dark amber when heme precursors form uroporphyrin‐like‐pigments. Treatment is primarily supportive: fluids (preferable 10% dextrose in 0.45% saline), antiemetics, analgesics, and anticonvulsants. Of note, many anticonvulsants are not safe in acute porphyria, including phenytoin, valproic acid, carbamazepine, clonazepam. Intravenous heme is the only specific treatment but is not widely available.

Protoporphyria occurs when there is bone marrow overproduction of protoporphyrin. It is typically diagnosed in early childhood, with toddlers develop pain, stinging, oedema, and itching of sun exposed skin often within 10 minutes of being in the sun but can be longer in adults. Total blood porphyrin over five times the upper limit of normal is diagnostic. Urine colour is normal as protoporphyrin is universally excreted into bile. This leads to complications such as gallstones and cholestasis. Treatment with oral beta‐carotene is most effective, but only works in <1/3 of cases. Activated charcoal, and colestipol are also trialled but often ineffective. Avoidance of sunlight is the main treatment for most patients, is associated with vitamin D deficiency in 50% of patients.

Bullous pemphigoid is a subepidermal blistering disorder that most commonly occurs in older adults. The classic skin lesions are urticarial plaques and tense bullae on the trunk and extremities. Intense pruritus is common, and lesions typically do not scar. Cutaneous lichen planus is most commonly expressed as an eruption of shiny, flat, polygonal, violaceous papules. Dermatitis herpetiformis is an autoimmune blistering disease associated with coeliac disease and characterised by intensely itchy polymorphous vesicular lesions located over the extensor surfaces, back, and scalp.

Bissell D, Anderson K, Bonkovsky H. Porphyria. New England Journal of Medicine. 2017;377(9):862–872.

https://www.nejm.org/doi/full/10.1056/NEJMra1608634

8. Answer: C

Rosacea is an inflammatory facial condition of unknown cause associated with high morbidity due to social avoidance, and mood disorder. Rosacea most commonly manifests in middle age, mostly effects women, and can present with flushing and telangiectasia, inflammatory papules and pustules, or a combination of both. Keratitis is commonly seen in rosacea, but is rarely severe enough to be vision threatening. Long‐term sequelae include phymatous changes, most commonly of the nose.

Despite the unclear pathophysiology, several anti‐inflammatory, and vasoactive medications have been shown to significantly improve symptoms associated with the condition. Topical medications blockading alpha‐receptors significantly reduce vascular symptoms – for example brimonidine and oxymetazoline. For inflammatory symptoms, medications such as metronidazole, ivermectin, azelaic acid have shown significant efficacy. For lesions refractory to topical therapy, combination with low‐dose oral doxycycline or tetracycline is indicated, and for cases refractory to this, low‐dose isotretinoin is effective. For inflamed phymatous changes, anti‐inflammatory treatments can be effective, but for more fibrosed lesions, ablative laser therapies can be effective.

van Zuuren E. Rosacea. New England Journal of Medicine. 2017;377(18):1754–1764.

https://www.nejm.org/doi/full/10.1056/NEJMcp1506630?af=R&rss=currentIssue&page=2&sort=newest

9. Answer: B

In developed countries, scabies epidemics occur primarily in nursing homes, prisons and other long‐term care facilities. Transmission of scabies is predominantly through direct skin‐to‐skin contact. Prevalence rates for scabies are higher in sexually active individuals, immunocompromised, and elderly patients. The S scabiei hominis mite that infects humans is female and is large enough (0.3–0.4 mm long) to be seen with the naked eye. Its life cycle occurs completely on the human, but the mite is able to live on bedding, clothes, or other surfaces at room temperature for 2–3 days, while remaining capable of infestation and burrowing.

Patients usually present with pruritus, erythematous papules, and vesicles in webbed spaces of the fingers, wrist, elbows, and scrotum. Burrows are a pathognomonic sign and represent the intraepidermal tunnel created by the moving female mite.

There are three types of scabies:

1 Classic scabies: Typically, 10–15 mites live on the host. After 4 weeks of primary infection and with subsequent infections, a delayed type IV hypersensitivity reaction to the mites and eggs occurs, which causes the classic skin eruption and its associated intense pruritus.

2 Crusted scabies is a distinctive and highly contagious form of the disease. In this variant, hundreds to millions of mites infest the patient, who is usually immunocompromised, elderly, or physically or mentally disabled and impaired. It can be confused with severe dermatitis or psoriasis because widespread, crusted lesions appear with thick, hyperkeratotic scales over the elbows, knees, palms, and soles. Serum IgE and IgG levels are high in patients with crusted scabies, but the immune reaction is not protective. Crusted scabies carries a higher mortality rate than the classic form of the disease, because of the frequency of secondary bacterial infections.

3 Nodular scabies occur in 7–10% of patients with scabies, particularly young children.

The diagnosis of scabies can often be made clinically in patients with a pruritic rash and characteristic linear burrows. The diagnosis is confirmed by light microscopic identification of mites, larvae, ova, or scybala (feces) in skin scrapings, and skin biopsy is not required.

Scabies treatment includes administration of a scabicidal agent such as permethrin, lindane, ivermectin. There is no single agent ranked most effective with respect to cure and control of adverse effects from the scabies infection.

Chandlera DJ. A Review of Scabies: An Infestation More than Skin Deep. Dermatology 2019;235:79–90.

https://www.karger.com/Article/FullText/495290

10. Answer: C

Organ transplant recipients are at a higher risk (up to a 100‐fold higher) for developing skin cancer compared to the general population. Heart and lung transplant patients develop skin cancer more frequently than liver or kidney transplant patients. The common skin cancers after solid organ transplant are squamous cell carcinoma (SCC), basal cell carcinoma (BCC), melanoma, and Merkel cell carcinoma (MCC). This higher risk is due to immunosuppression. Many centres advise transplant patients to check their skin monthly for worrisome lesions and have yearly dermatological review. Patients should practise adequate sun protection measures, including using sunscreen and wearing protective clothing and be aware of the significant UV exposure that can occur in all seasons.

Sunlight consists of two types of harmful rays that reach the earth: UVA and UVB rays. Overexposure to either can lead to skin cancer. In addition to causing skin cancer, UVA rays can cause age spots or solar lentigines, UVB rays are the primary cause of sunburn.

It is recommended to use a broad‐spectrum sunscreen with a Sun Protection Factor (SPF) of at least 30, which blocks 97% of the sun's UVB rays. Broad spectrum sunscreen can protect skin from both harmful UVA rays and the UVB rays. Higher‐number SPFs block slightly more of the sun's UVB rays, but no sunscreen can block 100% of the sun's UVB rays. High‐number SPFs last the same amount of time as low‐number SPFs and high‐number SPF does not allow you to spend additional time outdoors without reapplication. Sunscreens should be reapplied approximately every two hours when outdoors.

There are two types of sunscreen: (i) Chemical sunscreens, which work by absorbing the sun’s rays. They contain one or more of the following active ingredients, oxybenzone, avobenzone, octisalate, octocrylene, homosalate, or octinoxate, (ii) Physical or mineral sunscreens act like a shield deflecting the sun’s rays. They contain the active ingredients titanium dioxide, zinc oxide, or both, which are safe for sensitive skin. Using sunscreen can decrease skin’s production of vitamin D.

Iannacone MR. Effects of sunscreen on skin cancer and photoaging. Photodermatol Photoimmunol Photomed 2014; 30: 55–61. https://onlinelibrary.wiley.com/doi/full/10.1111/phpp.12109

11. Answer: B

The skin is made up of three layers, the most superficial layer is the epidermis and the layer below is the dermis, followed by the third layer of subcutaneous tissue. The epidermis is further divided into five layers in areas of thick skin, such as the palms and soles: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. While in areas of thinner skin, the epidermis has four layers, without the stratum lucidum.

The dermis is further divided into two layers, the papillary dermis (the upper layer) and the reticular dermis (the lower layer) which contains the vasculature. The skin is highly vascularised; there is an extensive network of larger blood vessels and capillaries that extend from regional branches of the systemic circulation to local sites throughout subcutaneous tissue and dermis, respectively. Therefore, it is likely that the excision has traversed the reticular dermis to cause profuse bleeding. In addition, there is an extensive lymphatic network that runs alongside many of the skin’s blood vessels, particularly those attached to the venous end of the capillary networks.

12. Answer: D

Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) are severe skin disorders characterised by mucosal involvement, extensive skin necrosis and epidermal detachment. SJS is classified by <10% body surface area (BSA) involvement, Overlap syndrome 10–20% BSA and TEN >30% BSA. It is usually caused by antibiotics, anticonvulsants, allopurinol, and anti‐inflammatory medications commenced 2–3 weeks prior to presentation.

Supportive care has been shown to be the most important treatment for patients with SJS/TEN. It should consist of managing skin wounds, haemodynamic stability, electrolyte balance, maintenance of airway and pain control. Guidelines suggest that covering the denuded skin can improve skin barrier function, reduce water and protein loss, limit microbial colonisation and promote reepithelialisation.

Systemic steroids were considered to be the primary treatment option for many years, however recent studies have reported a lack of efficacy and in some cases worsened mortality from increased risk of infection, delayed healing and prolonged hospitalisation. The use of IVIG has had controversial conflicting results. A recent meta‐analysis showed no difference in mortality when comparing patients who received IVIG compared to those who received supportive care. Although some studies have showed that higher dosages of IVIG may lower mortality.

There have also been several case reports with positive results for TNFα inhibitors such as Etanercept in the treatment of SJS/TEN. There is one published case series of 10 patients who responded well with complete reepithelialisation, however it will need further studies to validate these results. Cyclosporine is an immunosuppressive agent inhibiting CD8+ T cells. One study found a significant and beneficial effect of cyclosporine when compared to supportive care. Although it seems to be a promising treatment, it is contraindicated in patients with severe renal dysfunction, infection, malignancy, and sepsis. Patients with SJS/TEN often have secondary infection, organ dysfunction, and other comorbidities, which limits its use.

Duong T, Valeyrie‐Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. The Lancet. 2017;390(10106):1996–2011.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30378-6/fulltext

13. Answer: F

14. Answer: A

15. Answer: E

16. Answer: G

17. Answer: H

Dermatological emergencies are usually accompanied by severe and often striking visual appearance and are often indicative of systemic illness with high morbidity 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