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
