Skin

Question 1

Definitions of and organisms causing cellulitis and erysipelas

Answer 1

Infective spreading inflammation of skin and subcut tissue resulting in pain, erythema, oedema and warmth

• Cellulitis involves deeper dermis & subcut fat.
• Erysipelas involves upper dermis & superficial lymphatics.

Organisms

• Cellulitis = beta-haemolytic strep most commonly grp A strep (pyogenes), also S. aureus; gram neg aerobic bacilli in minority
  
  • violaceous colour and bullae suggests strep infection
• Erysipelas = most commonly beta-haemolytic strep
• Abscess = most commonly S. aureus, either methicillin-susceptible or MRSA

Contributing factors for cellulitis & abscess: diabetes, immunosufficiency, venous stasis, lymphoedema, obesity, pre-existing skin conditions eg psoriasis/eczema, tinea pedis

Question 2

Describe the pathophysiology and treatment of ingrown toenails.

Answer 2

Ingrown toenails (or onychocryptosis) occur when a spicule of the lateral nail plate pierces the lateral nail fold and penetrates into the skin, with subsequent foreign-body inflammatory reaction and secondary infection. The lateral great toenail is most commonly affected.

Characteristic signs and symptoms include pain, edema, exudate, and granulation tissue.

Predisposing factors include poorly fitting shoes, excessive trimming of the lateral nail plate, pincer nail deformity, and trauma.

Treatment options range from conservative (salt bath, re-direction, podiatry) to surgical excision and thermo-chemical ablation. Antibiotics have no proven role.

Question 3

Describe the pathophysiology of frostbite.

Answer 3

Following exposure to subfreezing temperatures, ice crystals form extracellularly. If freezing is rapid, ice crystals may also form inside cells. Fluid and electrolyte fluxes cause lysis of cell membranes with subsequent cell death. An inflammatory process ensues mediated by thromboxane A2, prostaglandin F2-alpha, bradykinins, and histamine. This leads to tissue ischemia and necrosis.

Question 4

Discuss wound healing, include molecular mediators in your answer.

Answer 4

1. Reactive
   
   • Haemostasis (coagulation pathways, PAF)
   • Inflammation (IL-1, IL-2, IL-8)
   • Chemotaxis (LB₄, C5_{<u><strong>a</strong></u>,} Chemokines)
   • Epithelial migration (macrophages)
2. Regenerative
   
   • Proliferation (VEGFR, PDGF, TGF-b, IFN-y)
   • Maturation
3. Remodelling
   
   • Contraction (Fibroblasts, MMPs)
   • Scarring (Fibroblasts, MMPs)
   • Remodelling of scar (Fibroblasts, MMPs)
     
     • Type III collagen replaced by Type I

Question 5

What is atypical mole syndrome?

Answer 5

Three or more of the following characteristics:

• Two or more clinically atypical naevi
• >100 naevi >2 mm diameter or >50 naevi if <20 or >50 years of age
• Naevi abnormally distributed (buttocks or dorsum of foot)
• Naevi in the anterior scalp
• Iris pigmented lesion(s)

AMS predisposes to melanoma; RR of 3-20 in the presence of atypical naevi so higher at the AMS end of the spectrum. May suggest a mutation in the MAPK pathway or heterozygosity of the CDKN2A gene.

Question 6

What is Familial Atypical Multiple Mole and Melanoma syndrome?

Answer 6

Familial Atypical Multiple Mole and Melanoma syndrome is an familial condition diagnosed by:

• Melanoma in 2 or more first or second degree relatives
• Many atypical naevi (usually more than 50)

Subsequent genetic research has demonstrated that many of these patients have an AD inherited condition characterised genetically by mutations in the CDKN2A gene, which codes for a series of checkpoint regulators.

Question 7

What are the suggested excision margins for melanoma according to

NZ and Australian Guidelines?

The evidence?

Answer 7

Evidence

• No benefit seen for margins >2cm regardless of size
• For in situ disease histologically complete resection rates are slightly higher with 9mm margins cf 5mm
• For lesions >2mm 1cm is worse than 3cm
• For lesions 1-2mm trend for 1cm worse than 3cm

SO

• Try and get 1cm for in situ disease
• Where feasible get 2cm for any lesion deeper than 1mm.

Question 8

Describe the pathophysiology of necrotizing soft tissue infection.

Answer 8

The infection usually begins via a break in the muco-cutaneous barrier; usually the skin.

Bacteria, aided by pathogenic factors such as hyaluronidase, lipase, collagenase (many sp.), streptokinase, and M-proteins (GAS), and alpha-toxin (clostridial sp.) spread throughout the layers of the skin.

Local inflammatory change also promotes microvascular occlusion which facilitates further spread of the infection.

M protein is an important virulence determinant of GAS; necrotising infection caused by GAS strains w M types 1&3 = assoc w strep toxic shock syndrome in ~50% cases. GAS strains of these & other serotypes can produce pyrogenic exotoxins, which induce cytotoxins –> contribute to shock, tissue destruction, organ failure. GAS infection is more often assoc w septic shock requiring tx w inotropes/vasopressors.

Question 9

What is Hydradenitis Suppurativa?

What areas are commonly affected?

What are the common symptoms?

Answer 9

• Hidradenitis suppurativa is a chronic, inflammatory skin disorder of the folliculopilosebaceous units characterized by the development of inflammatory nodules, pustules, sinus tracts, and scars, primarily in intertriginous areas (groin & axillae, also inframammary, perineal & perianal areas)
• Traditionally been considered the result of occlusion of apocrine glands by keratotic debris –> leads to bacterial proliferation, suppuration & spread of inflammation to surrounding subcut tissues –> subcut tracts & pits develop; infected tissues ultimately become fibrotic & thickened
• Physical pain, odor, chronic drainage, and disfigurement are common features of this disorder.

Question 10

What is your management of hydradenitis suppurativa?

Answer 10

Multimodality therapy

• Lifestyle changes:
  
  • Stop smoking
  • Dietary restrictions
• Medical therapy:
  
  • Antibiotics; Doxycycline 100mg PO BD 14 days
  • Steroids for severe disease
• Tailored surgery:
  
  • For acute disease, mainstay = I&D
  • Punch biopsy for smaller lesions
  • De-roofing taking only the affected folliculopilosebaceous units - PICO for dressing
  • Wide local excision and grafting
  • Liberal biopsies to exlcude malignancy
• NB 50% recurrence rate after WLE

Question 11

What is Merkel Cell Cancer?

How is it managed?

Answer 11

Merkel cell carcinoma is a rare, aggressive cutaneous malignancy that predominantly affected older, fair skinned adults, especially those who are immune-suppressed. It has a predilection for local recurrence and local lymph node metastases.

Although rare, New Zealand and Australia have some of the highest reported rates in the world, at ~1 per 100,000 in NZ. Risk factors for MCC include older age (18 per 100,000 in those above 85), light skin, and immune suppression, especially with mTOR drugs.

Merkel cell carcinoma (MCC) has been traditionally believed to arise from Merkel cells, which are located in the basal layer of the epidermis and hair follicles and are associated with skin mechanoreceptors. However, this hypothesis is controversial. An alternative hypothesis is that these tumours originate from an immature totipotential stem cell that acquires neuroendocrine features during malignant transformation. Recent data suggests they are linked to Merkel Cell Polyomavirus, a ubiquitous dsDNA virus.

(AEIOU) Diagnosis is difficult as the majority of patients are asymptomatic (88%) so a high level of suspicion is required. Most have a rapidly expanding lesion (63%), a minority are on immune suppression (~10%). Almost all patients are older than 50 (90%). UV exposure is present in 90%.

Staging is based on size (2cm) and whether the lesion has metastasised to regional or distant nodes. The 5 year survivals are 50%, 35%, and 15% respectively.

Wide local excision (1-2cm) and SNB are recommended for early disease, though SNB is less studies in this group. Many surgeons would not perform SNB for MCC larger than 2cm as adjuvant radiotherapy will be given any way. Locally advanced disease can be treated with surgery for the primary and lymphadenectomy for the nodal basin. Radiotherapy may be used in frail patients for both the primary and lymph nodes. Systemic treatment with biological therapy e.g. PD-L1 inhibitors are being studies but no high quality date exists yet.

Question 12

What is the role of topical therapy for cutaneous malignancy?

Answer 12

• Fluorouracil and imiquimod creams are topical treatments that may be used to treat some non-melanoma skin cancers, usually second-line to surgical excision
• These medicines work by destroying cancerous cells in the skin, resulting in a local reaction including erythema and erosion, followed by re-epithelisation of the skin
• Fluorouracil and imiquimod may be appropriate for the treatment of actinic keratoses, superficial BCC and SCC in situ
• Treatment regimens vary depending on the type of lesion, but fluorouracil and imiquimod creams are typically applied twice daily for up to 6-10 weeks, with an expected reaction after 1-2 weeks of treatment

Question 13

What is Kaposi’s sarcoma?

Answer 13

• Kaposi sarcoma (KS) is an angioproliferative disorder that requires infection with human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated Herpes virus (KSHV), for its development
• KS is classified into four types based upon the clinical circumstances in which it develops:
  
  1. Classic (the type originally described by Kaposi, which typically presents in middle or old age)
  2. Endemic (several forms described in Sub-Saharan indigenous African populations)
  3. Iatrogenic (typically seen in renal allograft recipients)
  4. AIDS-associated (epidemic KS)
• Treatment involves optimal care for the underlying pathology (AIDS, Immune suppression) and then control of symptoms as HHV-8 cannot be eradicated; this may be with:
  
  • Surgery
  • Radiation therapy
  • Cryotherapy
  • Chemotherapy
  • Immunomodulation with IFN-a

Question 14

What is an ulcer?

Answer 14

1. A breach in the epithelium of a tissue
2. A dimished ability of the tissue to heal
3. Acute and chronic inflammation

Question 15

Provide an overview of commonly used anti-thrombotic medications.

Answer 15

1. Warfarin
   
   • Vitamin-K reductase inhibitor
   • Affects II, VII, IX, X, Prot-C, Prot-S
   • Not safe in pregnancy
   • INR to measure
2. Heparin
   
   • Binds to, and potentiates, Antithrombin III
   • Inactivates Thrombin, Xa, and other proteases
   • Large molecule
   • Measured with aPTT
3. LMWH
   
   • More anti-Xa activity than anti-thrombin activity
   • 100% bioavailability subcut
   • Safe in pregnancy
4. Direct thrombin inhibitors
   
   • “Dabigatran” Rivaroxiban”
   • Recombinant derivative of leech saliva (hirudin)
   • Dabigatran is reversible and dialysable
   • Thrombin time to measure

Question 16

What is the differential for a cystic lesion of the dermis/epidermis?

Answer 16

Sebaceous/Epidermal cyst

Dermoid cyst

Trichilemmal csyt

Think about:

Dermatofibroma

Dermatofibrosarcoma protuberans

Question 17

How are wounds classified with regard to infection risk?

Answer 17

Clean

• 2% infection risk
• Elective, non-traumatic, primarily closed, no inflammation, no break in technique, body tracts not entered.

Clean-contaminated

• <10% infection risk
• Urgent or emergency case that is otherwise clean, elective opening of body tracts with minimal spillage and no infected fluids, minor technique break.

Contaminated

• 10-20%
• Non-purulent inflammation, gross intestinal spillage, infected tract entered, major break in technique, penetrating trauma <4 hours old, chronic open wounds

Dirty

• 20-40%
• Purulent inflammation, pre-operative perforation of infected tract, penetrating trauma >4 hours old.

Question 18

How are burns classified?

Answer 18

The traditional classification of burns as first, second, third, or fourth degree was replaced by a system reflecting the need for surgical intervention. Current designations of burn depth are superficial, superficial partial-thickness, deep partial-thickness, and full-thickness.

Question 19

How is frostbite or cold injury classified?

Answer 19

First degree

• Hyperaemia and oedema without skin necrosis

Second degree

• Large clear vesicle formation accompanies hyperaemia and oedema with partial thickness skin necrosis

Third degree

• Full thickness and s/c tissue necrosis occurs, commonly with haemorrhage vesicle formation

Fourth degree

• Full thickness skin necrosis including muscle and bone gangrene

Question 20

How are soft tissue sarcomas staged?

Answer 20

With difficulty…

The AJCC combine their TNM system with the French grading system (better than the NCI system) for grade to complete staging.

• T-staging
  
  • 5cm or less
  • 5-10cm
  • 10-20cm
  • Greater than 20cm
• N-staging / M-staging
  
  • Nodes or mets negative/positive.

Grade calculated by accounting for tumor differentiation, mitotic grade, and degree of necrosis.

Note that the tumour biology imparts far more prognostic information, so that STSs are now being indivdually graded such as GISTs, Kaposi sarcoma, dermatofibrosarcoma all have different systems.

Question 21

How are soft tissue sarcomas classified?

Briefly describe the lesions that characteristically make up each of these classes.

Answer 21

The most traditional classification for this histologically diverse group is:

• Extremity/trunk versus
• Retroperitoneal/visceral

Extremity/trunk:

• More common
• Malignant peripheral nerve sheath tumours, schwannomas, angiosarcomas, DFSP, and desmoids make up the bulk of these tumours.
• Amputation is becoming less common, mostly as a result of management through MDM
• Multi-modality therapy appears to be more effective for treatment; the optimum timing and nature of this is unclear. This includes the use of isoltated-limb-perfusion.
• Desmoids are increasingly being surveilled, consider Tamoxifen for adjuvant therapy.

Retroperitoneal/visceral:

• 15% are retroperitoneal
• Liposarcoma, Leiomyosarcoma, and MFH (undiff. pleomorphic sarcoma) make up the bulk of the retroperitoneal lesions.
• 75% of patients require visceral resection to complete negative margins.
• Data not as encouraging re multi-modality therapy.
• GIST makes up most visceral STS (stomach>SB>rectum).
• Leiomyosarcoma typically affects the retroperitoneum and uterus.

Question 22

Which melanoma patients should be discussed at MDM?

Answer 22

Patients with the following should be discussed at a MDM:

complex reconstruction cases, including MIS

• stages II (B and C) cases if management decisions

are not straightforward

• stages III and IV cutaneous melanoma cases
• desmoplastic melanoma
• melanoma in people under 25 years of age
• non-cutaneous melanoma.

Question 23

Who is offered a SNB in melanoma

Answer 23

T1b and above

i.e. any lesion above 0.8mm or with ulceration

(SNB in melanoma is carried out using triple localisation with preoperative lymphoscintigraphy and SPECT scan. Intra-operative localisation is performed with blue dye and a gamma probe.)

Question 24

Who is offered a completion LN dissection?

Answer 24

1. All patients with macroscopic nodal disease
2. SNB-positive patients with ≥5 mm of disease after appropriate staging and discussion at a melanoma MDM.

Question 25

Who is offered adjuvant treatment?

Answer 25

All patients with resected

1. Stage III or IV
2. Stage IIb / C (greater 2cm)

considered for adjuvant radiotherapy and/or adjuvant systemic treatment or enrolment in clinical trials.

Question 26

What is the expected LN positivity rate for intermediate thickness melanoma?

Answer 26

20%

Question 27

Describe the T-staging of melanoma.

Answer 27

Based on thickness of the melanoma.

New TNM system has an ulceration modifier.

Question 28

Describe the N-staging in melanoma

Answer 28

Based on number of nodes involved.

Newest AJCC system includes:

• A distinction between occult (SNB detected) and clinically detected (Nxb) nodes
• An in-transit modifier which maximises the N-stage ^i.e. becomes Nxc

Question 29

Describe the M-staging in melanoma

Answer 29

Based on anatomic site of metastases.

Newest AJCC edition has an LDH modifier which add Mxa/b/c (0 or 1).

Question 30

How is melanoma classified?

Answer 30

Melanoma can be classified based on growth pattern and invasion:

Superficial spreading melanoma

• Most common ~55% F>M 20-60 years
• Usually occurs in sun-exposed areas
• Typically on the trunk and proximal extremeties

Lentigo maligna melanoma

• Arises from lentigo maligna - long standing
• Sun-exposed areas of older patients
• Challenging due to the location but better prognosis overall

Nodular melanoma

• Dome-shaped, M>F, commonly on head and neck
• Develop an vertical growth pattern early
• Aggressive

Acral lentiginous melanoma

• Soles, palms, mucosa, subungal, perineal regions
• Commoner in dark-skinned races
• Often large and advanced at time of diagnosis
• Poor prognosis

Desmoplastic malignant melanoma

• Head and neck most common site
• Characterised by melanocytes and stromal fibrosis
• May be amelanocytic

Non-cutaneous melanoma

• May occur anywhere that neural creast cells migrate
• Ocular, mucosal (oral, anal, GI tract)

Question 31

What are the histological layers of the skin and subcutaneous tissue?

Answer 31

Stratum corneum

• Dead skin cells

Epidermis

• Stratum corneum
• Stratum lucidum
• Stratum granulosum (where Breslow is taken from)
• Stratum spinosum
• Stratum basale

Dermis

• Papillary dermis (subcuticular layer)
• Reticular dermis

Hypodermis

• Fat, blood vessels, nerves, etc
• Sweat glands
• Apocrine glands
• Sebaceous glands

Question 32

How is Hydradenitis Suppurativa classified?

How is it useful?

Answer 32

The Hurley clinical staging system:

Stage I - Mild

• Abscess formation (single or multiple) without sinus tracts and cicatrization/scarring

Stage II - Moderate

• Recurrent abscesses with sinus tracts and scarring, single or multiple widely separated lesions

Stage III - Severe

• Diffuse or almost diffuse involvement, or multiple interconnected sinus tracts and abscesses across the entire area

Stage I and II can be treated with antibiotics and anti-inflammatories.

Stage III is likely to require antibiotics and IV steroids +/- surgical debridement.

Question 33

How are naevi classified?

Answer 33

Congenital naevi: (clinical classification)

• Small <15mm
• Medium 15-199mm
• Giant >200mm
• Positional ^e.g. Mongolian Spot, Naevus of Ota
• Cafe-au-lait spots, Freckling.

Acquired naevi: (histological classification)

• Junctional naevus (melanocytes nest on DEJ)
• Dermal naevus (melanocytes dermal side DEJ)
• Compound naevus (melanocytes either side DEJ)

Acquired naevi: (clinical classification)

• Typical (uniform)
• Atypical (ABCDE changes)
• Blue naevus (navy blue spot)
• Halo naevus (starburst or globules on dermoscopy)

Question 34

What are the risk factors for melanoma?

Answer 34

• Age and gender (male more likely)
• Skin phenotype; Fitzpatrick I and II more likely
• Pre-existing melanocytic naevi and large naevi
• Sun-exposure
  
  • UV-B and UV-A
  • Especially in bursts or before 35 year of age
• Underlying genetic disorder
  
  • Xeroderma pigentosum
  • CDKN4 and CDKN2A mutations causing FAMMM
• Immunosupression
• Irradiation

Question 35

What are the sub-headings on a histopathological report for Melanoma?

Answer 35

1. Macroscopic description and dimensions
2. Breslow thickness
3. Margins of excision
4. Mitotic rate
5. Presence or absence of ulceration
6. LVI
7. Nerve sheath infiltration
8. Lymphocytic infiltration
9. Microsatellites and in-transit metastases
10. Regression
11. Desmoplasia
12. Histological cell type and growth pattern
13. Immunohistochemistry (S-100, Melan-A, HMB-45)
14. Associated benign melanocytic lesion.

Question 36

What are the different types of BCC?

Answer 36

The clinical presentation of BCC can be divided into three groups, based upon lesion histopathology:

• Nodular
  
  • ~60% of cases
  • Pearly rolled edges, central ulcer
  • May be pigmented
• Superficial
  
  • ~30% of cases, more common in men
  • Plaque-like with fine telengectasia
  • Slowly enlarging
  • May be pigmented
• Morpheaform
  
  • ~5-10%
  • Typically smooth, flesh-colored, or very lightly erythematous papules or plaques that are frequently atrophic
  • They usually have a firm or indurated quality with ill-defined borders.
  • Hardest to diagnose and accurately excise.

“Baso-squamous” lesions are probably best considered a basal variant of SCC…

Question 37

What excision margins will you accept for:

BCC?

SCC?

Answer 37

• For well differentiated nodular BCC 0.3-0.5mm is acceptable.
• If a BCC is morpheaform or poorly differentiated, then a wider margin of 1cm should be attained.
• Cosmetic outcome and width or margin are competing interests.
• Note that 60% of margin positive BCC do not recur.
• SCC requires at least 5mm if invasive, 10mm is preferrable.
• SCC is more likely to recur with positive margins and given its propensity to metastasize then re-excision is the standard.

Question 38

The overall favourable prognosis and low risk of metastases have limited formal TNM staging for both SCC and BCC.

What “high-risk” features may be used to risk-stratify patients with these cutaneous malignancies?

Answer 38

• Size
  
  • >20mm on trunk
  • >10mm on forehead and neck
  • >6mm on face
• Borders
  
  • Poorly defined worse
• Differentiation
  
  • Poorly defined worse
• Perineural or lymphovascular invasion
• Background of immune-suppression, previous irradiation, chronic inflammation.

Question 39

Which patients need staging with CT PET and MRI brain in melanoma?

Answer 39

> Stage IIIa (above 3 SNB positive LN, unless completion LN dissection is planned)

TIIb+C (T3b and T4a/b) = discuss at MDM

Stage IV + PET CT is recommended if it will change management

Question 40

What is a dermoid cyst?

What are the histological findings?

What distinguishes dermoids from teratomas?

Answer 40

Dermoid cysts are congenital subcutaneous lesions that are usually distributed along embryonic fusion lines of the facial processes or within the neural axis.

The characteristic histologic findings include a lining of epidermis and evidence of adnexal structures, such as hair follicles, sebaceous glands, and eccrine and apocrine sweat apparatus.

A dermoid is composed only of dermal and epidermal elements, whereas teratomas have mesodermal and endodermal elements

Question 41

What are seborrheic keratoses?

Answer 41

A benign neoplasm of the skin.

Overgrowth of the basal layer of the epidermis occurs. dark staining basal cells are therefore raised above surrounding the skin. There is a semi-transparent, oily appearance.

Question 42

What are the phases of a typical keratoacanthoma?

Answer 42

1. Proliferative - 2 to 4 weeks - alarming
2. Maturation - capped by a keratin cone
3. Involution - resolves over a few months

Question 43

How does Efudix work?

How does Imiquimod work?

Answer 43

• Efudix is topical 5-Fluorouracil
  
  • This is a chemotherapeutic agent which inhibits production of thymidine and so prevents DNA replication
• Imiquimod is a immune-modulating agent on TLR-7
  
  • Activation of the Toll-Like-Receptor yields enhanced anti-tumoural activity

Question 44

Provide an overview of treatment of metastatic melanoma.

Answer 44

• Old-fashioned chemotherapy are no longer used.
• Targeted therapy
  
  • Target MAPK mutations
  • BRAF mutationsin 40-60% (younger patients)
  • NRAS mutations in 20-30%
  • c-KIT mutations rare
  • Dabrafenib and Vemurafenib
  • Combine BRAF and MEK inhibitors to improve efficacy and reduce S/E
• Immune-checkpoint inhibition
  
  • Anti CTLA4 - Ipilumimab (may cure!)
  • Anti PD-1 - Pembrolizumab and Nivolumab
  • Both work, PD-1 are better and have less side effects; hence Pembrolizumab/Nivolumab are funded by PHARMAC.

With new therapies and combinations the 1-2 year survivals have been increased to 90-80% with some living to 3 years.

Question 45

What are necrotising soft tissue infections and how are they classified?

Answer 45

• include necrotising forms of fasciitis, myositis & cellulitis; characterised by fulminant tissue destruction, systemic signs of toxicity & high mortality
  
  • can include involvement of the epidermis, dermis, subcut tissue, fascia & muscle
• classification
  
  • can be classified based on microbiology, by presence/absence of gas in tissues & by what structures are involved
  • nec fasc
    
    • polymicrobial (type 1) aka synergistic necrotising cellulitis - gas in soft tissue
    • monomicrobial (type 2)
  • nec myositis
    
    • clostridial myonecrosis (gas gangrene) - gas in soft tissue
    • necrotising myositis due to group A strep or other beta-haemolytic strep
  • nec cellulitis
    
    • clostridial - gas in soft tissue
      
      • traumatic (70%) or spontaneous
    • nonclostridial anaerobic (creptiant) cellulitis (polymicrobial) - gas in soft tissue

Question 46

Discuss the types and presentation of nec fasc

Answer 46

• Type I (polymicrobial) usu occurs in older people & those w underlying comorbidities esp T2DM, PVD
  
  • typically at least 1 anaerobic species (eg Bacteroides, Clostridium) + enterobacteriaeae (eg E coli, Enterobacter, Klebsiella) + one or more facultative anaerobic strep
    
    • Fourniers caused by these, may occur as breach in integrity of GI or urethral mucosa
    • necrotising infection of H&N usu caused by mouth anaerobes (eg Fusobacteria, anaerobic strep, Bacteroides, spirochetes) - following oral surgery or dental infection
• Type II (monomicrobial) - may occur in any age & in healthy people
  
  • usu GAS or other beta-haemolytic strep; also Staph aureus
    
    • in half, no clear portal of entry; likely haematogenous translocation from throat (asymptomatic or symptomatic pharyngitis) to a site of blunt trauma or muscle strain
  • Vibrio vulnificus - traumatic injury assoc w sea water or ingestion of contaminated oysters
  • Aeromonas hydrophila - traumatic injury assoc w fresh water

most commonly extremities (60%), perineum (40%), trunk (25%)

Question 47

What are the clinical features of necrotising fasciitis?

Answer 47

• Most commonly involves extremities lower > upper
• Usually presents acutely over hours; rarely subacutely over days
• Rapid progression to extensive destruction can occur –> systemic toxicity, limb loss and/or death
• Fever, tachycardia, systemic toxicity (GAS espec)
• Local
  
  • erythema (w/o sharp margins), oedema extending beyond visible erythema, severe pain (out of proportion in some), fever, crepitus (type 1), skin bullae/necrosis/ecchymosis
  • subcut tissue may be firm & indurated such that underlying muscle groups can’t be palpated distinctly - marked oedema may produce a compartment syndrome w complicating myonecrosis requiring fasciotomy
  • progresses rapidly over several days w changes in skin colour from red-purple to patches of blue-grey –> skin breakdown w bullae & frank cutaneous gangrene
  • in nec fasc, diminished sensation to pain develops in involved area due to thrombosis of small blood vessels & destruction of superficial nerves in subcut tissue; may precede appearance of skin necrosis
  • Fournier: typically begins abruptly w severe pain in perineum & may spread rapidly to ant abdo wall & gluteal muscles
  • H&N: fasciitis can spread to face, lower neck, mediastinum; can also get Ludwig’s angina (submandibular space infection) & Lemierre syndrome (septic thrombophlebitis of jugular vein)

Question 48

What is the predictive scoring system for nec fasc?

Answer 48

LRINEC score - Lab Risk Indicator for Nec Fasc

uses WCC, Hb, Na, glucose, creatinine, CRP

but has performed poorly in external validation - if clinically suspicious/crepitus/sick, operate

some say if WCC & Na both normal, nec fasc unlikely

CT can be useful for dx NSTI if don’t have classic signs (crepitus, rapid progression, severe pain out of proportion) & don’t have high suspicion but also not improving after 12-24hrs abx; but shouldn’t delay surgery when crepitus or sick; presence of gas in soft tissue which is seen most frequently in clostridium infection or polymicrobial (type I) - highly specific for NSTI & should immediately explore surgically.

Question 49

Intra-op findings for nec fasc

Answer 49

Swollen & dull-grey appearance of fascia, thin exudate w/o clear purulence & easy separation of tissue planes by blunt dissection. Liquefactive necrotic tissue or pus can also be found between fascial planes.

At operation if clinical dx less convincing, “the finger test” - 2cm incision in skin, to deep fascia –> lack of bleeding/exudate –> insert index finger; if subcut tissue easily dissected off the fascia (to which it is normally densely adherent), pathognomonic for nec fasc

Question 50

Discuss categories of Clostridial soft tissue infections

Answer 50

• Clostridial soft tissue infections include wound contamination, anaerobic cellulitis, myonecrosis (gas gangrene) & nec fasc
  
  • wound contamination w soil containing clostridial spores or vegetative organisms may occur; but doesn’t necessarily lead to infecction
  • anaerobic cellulitis: gas produced locally & extends along fascial planes; bacteraemia & invasion of healthy tissue (incl muscle) doesn’t occur; mortality low w appropriate mx incl prompt removal of devitalised tissue
  • myonecrosis: distinguished from above by progressive invasion & destruction of healthy muscle & other soft tissues
  • nec fasc (polymicrobial)

Question 51

Discuss gas gangrene

Answer 51

• Gas gangrene aka Clostridial myonecrosis
• life-threatening muscle infection that develops either continuosuly from area of trauma or haematogenously from GIT w muscle seeding
• classification
  
  • traumatic (70%) - usu caused by Clostridium perfringens (80%)
  • spontaneous - usu Clostridium septicum
• Clostridium species = widespread in nature due to ability to form endospores; commonly found in soil & marine sediments as well as human & animal intestinal tracts
• Traumatic gas gangrene:
  
  • Traumatic wounds w vasc compromise (espec deep penetrating injuries eg knife wounds, GSWs, crush injuries) create anaerobic environment ideal for proliferation of clostridia - common in wars, natural disaster victims, also bowel/biliary tract surgery, abortion, retained placenta, prolonged rupture of membranes etc
  • Trauma introduces organisms (vegetative or spore forms) directly into deep tissue; if trauma compromises blood supply, anaerobic environment forms which is optimal for growth of clostridial organisms –> necrosis of tissue can develop within hours of injury & progresses rapidly in absence of treatment
  • Many extracellular toxins produced by C perfringens; alpha and theta toxins implicated in pathogenesis; alpha toxin largely responsible for both the widespread tissue necrosis & the characteristic absence of a tissue inflammatory response
  • Shock assoc w gas gangrene may be attributable to both direct & indirect effects of alpha & theta toxins
    
    • alpha toxin directly suppresses myocardial contractility & may contribute to profound hypotension
    • theta toxin reduces systemic vascular resistance (pts w gram neg sepsis compensate for hypotension by markedly increasing cardiac output, but this adaptive mechanism may not be possible in setting of shock due to C perfringens given neg inotropic effect of alpha toxin)
• Spontaneous gas gangrene:
  
  • usu haematogenous seeding of muscle w bacteria (C Septicum) from a GI portal of entry
  • C septicum can grow in normal tissues; doesn’t require anaerobic conditions; produces multiple exotoxins but mechanism by which these contribute to pathogenesis unknown
• diagnosis requires demonstration of large gram-variable rods at site of injury (Clostridia can appear both gram +ve and gram -ve when stained directly from infected tissues but gram +ve when obtained from culture media)

Question 52

How does a VAC dressing work?

Answer 52

Negative pressure wound therapy:

1. maintains moist, closed-wound environment
2. manages excess exudate
3. manages excess exudate & helps to prepare a wound bed for skin grafts or tissue flaps by stimulating formation of granulation tissue

Due to constant uniform positive pressure applied to wound bed, also an excellent bolster over skin grafts.

Question 53

What is pilonidal disease?

Answer 53

An acquired disease resulting from a foreign body reaction to extruded hair in the skin; most commonly at the upper part of the natal cleft of the buttox, but other areas eg umbilicus & interdigital spaces can be affected

The presence of hair in the gluteal cleft seems to play a central role in the pathogenesis: as a person sits/bends, the natal cleft stretches, damaging or breaking hair follicles & opening a pore or ‘pit’; debris and loose hairs from region tend to gether towards natal cleft due to anatomy & suction of buttocks on movement –> these hairs migrate into pits/pores and get trapped –> FB reaction & keratin plugs/other debris may contribute further to inflammation –> creation of sinus tracts

Cavities may contain hair, debris & granulation tissue; pilonidal cavities aren’t true cysts & lack a fully epithelialised lining, however the sinus tracts may be epithelialised. Sinuses can get secondarily infected forming an abscess –> spreads along tract & may rupture spontaneously or require operative drainage.

Question 54

What are the elective operative options for pilonidal disease?

Answer 54

• Some prefer to excise all pilonidal sinus tracts down to level of sacrococcygeal fascia; others only unroof & debride the tracts w/o excising them; optimal technique debated but normal tissue should be preserved as much as possible to facilitate wound mx - higher vols of excised tissue assoc w increased complication & recurrence rates
• Only operate on symptomatic disease bc of morbidity with procedures
• Options include
  
  • Laying wound open to heal by secondary intention - prolonged healing time but reduced recurrence risk
    
    • Simple excision of subcut tract (sinectomy/sinustomy)
    • Wide excision down to sacral periosteum +/- marsupialisation of wound (areas of midline pits & sinuses excised & wound decreased in size by suturing wound edges to fibrous base of wound) - longer healing times
    • +/- NPWT if larger defects
  • Excision and primary closure +/- flap = shorter healing time & return to work but increased complications & recurrence rates
    
    • Fewer recurrences and wound infections and faster healing with off-midline closure though optimal procedure not been identified at randomised trial - preference
      
      • theory = natal cleft is anatomical trough w neg pressure in natal cleft produced by movement of buttocks; any wounds in midline will preferentially gather loose hairs in wound, predisposing midline wounds to recurrence; techniques of off-midline closure change natal cleft contour & disperse suction pressure over wider area, thereby decreasing likelihood of loose hair implanting in healing wound
    • Karydakis flap: uses a mobilised fasciocutaneous flap secured to sacrococcygeal fascia w lateral sutures to achieve off-midline wound closure - recurrence <5%, wound complication 7-21%
    • Bascom ‘cleft lift’: preserve fat on both sides & bring a thin flap (no deeper than a mastectomy flap) across the midline for off-midline closure + cleft obliteration - primary healing rates 80-96%, recurrence rate 0-17%
    • Rhomboid (Limberg) flap - rotational fasciocutanoeus flap that permits off-midline closure & flattening of cleft. Recurrence 0-6%, infection 0-6% (most do one of top 2 first)

Question 55

Discuss keloids and hypertrophic scars

Answer 55

Keloids and hypertrophic scars represent an excessive tissue response to dermal injury characterised by local fibroblast proliferation and overproduction of collagen.

Keloids are fibrous growths that extend beyond the original area of injury to involve the adjacent normal skin.

Hypertrophic scars may have a similar clinical appearance, but in contrast with keloids, remain confined within the boundaries of the wound area and tend to regress spontaneously over time.

Pathogenesis incompletely understood: alterations in usu sequence of wound healing influenced by multiple local and genetic factors. Essentially an overactive ‘regenerative’ phase of healing, w abnormal interaction of TGF-b and VEGF, w abnoraml fibroblast and collagen interplay

More common in women and African or Asian

1. Avoid: tension free, sensible location scars, Silicone gel sheets
2. Analgesia if painful
3. Intra-lesional steroids or 5-FU (most commonly used treatment = intralesional triamcinolone acetonide at conc of 10-40mg/mL)
4. Cryotherapy
5. Excision with above
6. Radiotherapy

Question 56

Describe the role of adjuvant immune checkpoint therapy in melanoma

Answer 56

• Can be used for metastatic (Stage IV) disease - funded in Aus/NZ
• Can be used for node-positive (Stage III) disease - not currently funded (register for trials)
• Keynote-6 demonstrated that Pembrolizumab (Keytruda, PD-1-mAb) is superior to Ipilumimab (CTLA4-mAb); 40% OS at 4 years for Pembro.
• Keynote-54 demonstrated that Pembrolizumab was superior to placebo for Stage III disease; 75% versus 60% DFS at 15 months
• Checkmate; Nivolumb+Ipilumimab or Nivolumab alone versus Ipilumab alone; Combination is better but more side effects.