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1
Q

What is the definition of hyperlactataemia and lactic acidosis?

A

Hyperlactatataemia = serum lactate >2
Lactic acidosis = serum lactate >4; even in the absence of overt acidemia

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2
Q

How do you differentiate Type A from Type B Lactic Acidosis?

A

Type A Lactic Acidosis = caused by impaired tissue oxygenation

Type B Lactic acidosis = not caused by impaired tissue oxygenation

Therefore Type A usually has manifestations of hypoperfusion/shock incl reduced urine output, hypotension, cool or clammy extremities, altered mental status

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3
Q

What are the main causes of Type B Lactic Acidosis?

A

1) Diabetes - secondary to ketoacidosis or metformin toxicity
2) Malignancy - incl lеukеmia, lymрhoma, and solid malignancies
3) Alcoholism - esp chronic, severe alcoholism
4) Methanol and ethylene glycol poisoning
5) HIV antiretroviral medication-induced mitochondrial dysfunction
6) Beta-adrenergic therapy - eg salbutamol
7) Inherited mitochondrial disorders eg MELAS (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like episodes syndrome
8) Thiamine deficiency
9) Propofol therapy
10) Linezolid therapy

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4
Q

What is Yellow Nail syndrome?

A

An uncommon disorder characterized by the triad of chronic lung disease; lymphedema; and slow-growing, yellow nails without a cuticle or lunula

Nails progressively thicken, becoming opaque and curved with loss of the lunula and cuticle

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5
Q

What is Yellow Nail syndrome typically related to?

A

Chronic respiratory illness (esp pleural effusions and chronic bronchitis) and lymphoedema
Rarely assoc with RA, internal malignancy and immunodeficiency

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6
Q

How do you treat Yellow Nail syndrome?

A

Treat underlying condition
Oral Vitamin E
Oral Zinc
Oral itraconazole

Most treatments disappointing

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7
Q

What percentage of patients with pulmonary sarcoidosis have skin involvement?

A

20-30%

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8
Q

What percentage of patients with cutaneous sarcoidosis have other organ involvement?

A

70%

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9
Q

How do you treat cutaneous sarcoidosis?

A

Topical steroids
Consider MTx if severe

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10
Q

What is cutaneous T cell lymphoma?

A

A diverse group of neoplasms of skin-homing T cells with great variation in appearance, histology, immunophenotype and prognosis

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11
Q

What is the most common type of T cell lymphoma?

A

Mycosis fungoides - represents half of cases

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12
Q

What is the classical presentation of mycosis fungoides?

A

Poikilodermatous patches and plaques typically in bathing-suit distribution

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13
Q

What is the 5 year survival in Mycosis fungoides?

A

88%

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14
Q

What are Neutrophilic Dermatoses?

A

A heterogenous group of disorders with overlapping clinical and histologic findings that are often assoc with internal diseases eg haem malignancy, dyscrasias, monoclonal gammopathy, IBD, RA

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15
Q

What is the classic appearance of neutrophilic dermatoses?

A

Infiltrated papules, nodules, pustules +/- infiltrates affecting eyes, joints, bones, lung, liver, brain and lymph nodes

Key includes violaceous and undermined edges and display pathergy (trauma worsens extent of problem, so do not debride)

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16
Q

What is Sweet Syndrome?

A

Acute febrile neutrophilic dermatosis

Infiltrated erythematous plaques and bullae favouring head/neck + constitutional symptoms

Most commonly secondary to AML, IBD, autoimmune disorders, drugs (azathioprine), pregnancy, infections (strep, GI yersiniosis)

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17
Q

What is the treatment and prognosis of Sweet Syndrome?

A

Treat underlying condition
High dose steroids
Supportive tx of fever

Resoles in 5-12 weeks but may recur

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18
Q

What is pyoderma gangrenosum?

A

The most common form of Neutrophilic Dermatosis

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19
Q

What is Anetoderma?

A

Reactive phenomenon commonly assoc with autoimmune disorders (Graves, Lupus, Sjogren’s), HIV, leprosy, chickenpox, cutaneous B-cell lymphoma, infantile haemoangioma

Presents with focal atrophic plaques - buttonhole sign (on pinching)

Hard to treat

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20
Q

What is Vitiligo?

A

Loss of melanocytes

Affects 0.5-1% of population

Assoc with autoimmune thyroid disease, T1DM, pernicious anaemia, Addison disease, SLE, RA, psoriasis, alopecia areata

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21
Q

How do you treat Vitiligo?

A

Topical steroids or calcineurin inhibitors
Narrowband UVB

Sometimes in recalcitrant issues requires systemic steroids, surgical grafting, depigmentation therapy

Camouflage make-up

However not treating at all is also an option

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22
Q

How does Cryoglobulinaemia present?

A

Acral cyanosis
Severe Raynaud’s with ulceration
Purpura
Livedo
Arterial thrombosis
Ulcers
Arthralgias/arthritis

May have systemic manifestations incl
membranoproliferative GN
Interstitial lung infiltrates
Sensory neuropathy
Abdominal pain

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23
Q

What conditions is Cryoglobulinaemia assoc with?

A

Haematological malignancies incl multiple myeloma, CLL, Waldenstrom’s

Autoimmune incl RA, SLE, systemic sclerosis, vasculitis, glomerulonephritis

Infection - hep A/B/C

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24
Q

How do you treat Cryoglobulinaemia?

A

Treat underlying condition
Keep warm
Rituximab for Hep-C assoc disease
Plasmapharesis + cytotoxic agent if life threatening complication

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25
What are some of the skin diseases related to HIV?
Disseminated candidiasis Seborrhoeic dermatitis Oral hairy leukoplakia Herpes zoster Psoriasis (hard to treat) Kaposi sarcoma Eosinophilic folliculitis Molluscum contagiosum Cryptococcosis Histoplasmosis Large perianal HSV/CMV ulceres
26
What cutaneous reaction classically occurs with Zidovudine (for HIV tx)?
Nail dyspigmentation
27
What genotype is assoc with increased risk of DRESS syndrome?
HLA-B*5701
28
What genotype is assoc with increased risk of Steven Johnson Syndrome?
HLA-B*3505 in non-caucasians
29
What is erythema multiforme?
An acute self-limited disease characterised by abrupt onset of symmetrical fixed erythematous papules and target lesions EM major - has mucosal involvement EM minor - no mucosal involvement
30
What are the typical triggers/preceding infections for Erythema Multiforme?
HSV/VZV Mycoplasma pneumoniae EBV CMV Hepatitis Parvovirus HIV
31
How do you treat Erythema Multiforme?
Supportive treatment - usually resolves within 2-3 weeks
32
What is the difference between SJS and TEN?
SJS <10% BSA of epidermal detachment TEN >10% BSA
33
What are the most commonly implicated drugs in SJS/TEN?
Allopurinol NSAIDs Antibiotics Anticonvulsants Onset is 7-21 days after commencing medication
34
How does SJS/TEN classically present?
Prodrome of URTI, fever, skin pain Erythematous macules coalescing into sheets, duskiness Mucosal involvement (usually painful) Epidermal detachment (Nikolsky sign - skin desquamates when apply pressure to skin)
35
How do you treat SJS/TEN?
Immediate cessation of drug Supportive care IVIG Analgesia DVT prophylaxis Mortality rate is 1-5% for SJS, 25-35% for TEN
36
What drug and what genotype are implicated in the classical association between Asian (esp Han chinese) and SJS/TEN ?
Carbamazepine HLA-B*1502
37
What is erythema nodosum?
Inflammation of the fat, commonly affecting females between 20-40yo Presents with tender bright red macules which fade to purple Can have assoc fever, arthralgia, lethargy, abdo pain, diarrhoea
38
What conditions are assoc with Erythema Nodosum?
IBD Sarcoidosis Malignancy Pregnancy Infections - strep, TB, yersinia, mycoplasma Medications - OCP
39
How do you diagnose erythema nodosum?
Clinical diagnosis
40
How do you treat Erythema Nodosum?
Treat underlying condition Bed rest Compression Leg elevation NSAIDs for pain Takes 2-4 weeks to resolve
41
Asian patients with what polymorphism are at increased risk of phenytoin-induced DRESS syndrome?
CYP2C9*3
42
Han Chinese patients with what HLA gene are at increased risk of Allopurinol induced DRESS syndrome?
HLA-B*5801
43
What HLA allele is assoc with increased risk of Dapsone or Cotrimoxazole-induced DRESS syndrome?
HLA-B*13:01
44
What are the high risk drugs for DRESS syndrome?
Aromatic AEDs incl carbamazepine, phenytoin, Lamartine Allopurinol Vancomycin Sulfonamide antibiotics Anti-TB drugs Dapsone Mexilitine Minocycline
45
What is the pathogenesis of DRESS syndrome?
Incompletely understood but thought to be T cell mediated hypersensitivity reaction One part due to drug specific immune response The other part is due to reactivation of viral infection involving the Herpesviridae family (eg, HHV-6, HHV-7, Epstein-Barr virus [EBV], cytomegalovirus [CMV])
46
What is the most common virus reactivated in association with DRESS syndrome?
HHV6
47
What is the typical latency period between drug exposure and symptom onset in DRESS syndrome?
2-8 weeks
48
What is the typical rash in DRESS syndrome?
A polymorphic evolving intensely erythematous maculopapular eruption that may progress to a coalescing erythema Typically symmetrical and extensive involvement of trunk and arms with >50% of BSA
49
What symptom involving the face is often striking in patients with DRESS syndrome?
Facial oedema
50
Is mucosal involvement present in DRESS syndrome and if so, how does it compare to SJS/TEN?
Yes - but tends to be milder than SJS/TEN
51
Is eosinophilia required for the diagnosis of DRESS syndrome?
No - indeed it is not present in a significant subset of patients
52
What are the Systemic Symptoms in DRESS syndrome?
Fever Lymphadenopathy Haematological abnormalities - eosinophilia - elevated WCC (neu, lymph, mono) - atypical lymphocytosis However can also have Lymphopenia and thrombocytopenia
53
Is organ involvement common in DRESS syndrome?
Yes - 90% of affected patients have one organ involved, 30% have 2
54
What is the most common visceral organ involved in DRESS syndrome?
Liver - often manifests as mild, transient LFT derangement
55
What is the most common renal manifestation of DRESS syndrome?
Acute interstitial nephritis (10-30%)
56
Kidney involvement in DRESS is more common when associated with which medication?
Allopurinol
57
What is the most severe form of cardiac involvement in DRESS syndrome that is associated with a 50% mortality rate?
Acute necrotising eosinophilic myocarditis
58
What are the features of severe DRESS syndrome?
Significant Cytopenias / pancytopenia Rapidly progressive/massive eosinophilia or atypical lymphocytosis Major kidney failure Liver enzymes >15x ULN Other organ involvement eg heart, lungs, CNS
59
Viral reactivation of which virus is assoc with poorer prognosis in DRESS syndrome?
CMV
60
How long does the rash take to resolve in DRESS syndrome?
On average 7 weeks
61
What are some important points to remember about the diagnosis of DRESS syndrome?
important to recognize that DRESS is a dynamic process, and characteristic features are not all present concurrently. It is also possible, though uncommon, for patients with DRESS to have no or minimal cutaneous involvement (<5 percent), absent eosinophilia, and mild, systemic symptoms or organ involvement
62
What is the diagnostic criteria for DRESS syndrome?
The RegiSCAR score: Fever Lymphadenopathy Eosinophilia Atypical lymphocytes Skin involvement Organ involvement Resolution >15 days
63
Which biomarker may be elevated in DRESS and can help differentiate it from SJS/TEN?
Thymus and Activation-Regulated Chemokine (TARC) level
64
Why is a skin biopsy performed in DRESS syndrome?
To exclude differentials - skin biopsy findings in DRESS are non specific
65
Which biomarker may be elevated in DRESS and can help differentiate it from SJS/TEN?
Thymus and Activation-Regulated Chemokine (TARC) level
66
Is patch testing helpful in DRESS syndrome?
May be positive in 30-60% and help establish drug causality However invariably negative in allopurinol and sulfasalazine
67
What feature(s) may help differentiate DRESS syndrome from an Exanthematous drug reaction?
Systemic symptoms in exanthematous drug reactions tend to be mild and latency period shorter
68
How does Acute Generalised Exanthematous Pustolosis (AGEP) present?
AGEP presents with an extensive eruption of hundreds to thousands of pinpoint, nonfollicular pustules within hours of drug exposure
69
How do you treat DRESS syndrome?
Identify and cease offending drug Supportive care Mild-mod - topical steroids Severe - systemic steroids Refractory - cyclosporin, consider IVIG, IL-5, JAKi
70
What is the estimated mortality from DRESS syndrome?
2-10%
71
What is the prognosis of DRESS syndrome?
The majority of px recovering completely in weeks to months However - risk of death 2-10% - risk of flares - risk of relapse - risk of autoimmune disease incl T1DM
72
What are SJS/TEN ?
severe cutaneous adverse reactions characterized by extensive necrosis and detachment of the epidermis. Mucous membranes are affected in more than 90 percent of patients, usually at two or more distinct sites
73
What defines SJS cf TEN?
SJS = <10% BSA TEN = >30% BSA 10-30% BSA = SJS/TEN overlap
74
What are the risk factors for SJS/TEN?
HIV Connective tissue disease Malignancy Older age Black or Asian ethnicity Renal impairment
75
What is the mortality of SJS/TEN?
23%
76
What drugs are strongly associated with SJS/TEN?
Similar to DRESS Allopurinol Lamotrigine Phenytoin Carbamazepine Sulfasalazine Sulfamethoxazole Phenobarbital Oxicam NSAIDs eg piroxicam Immune checkpoint inhibitors
77
78
What are some of the key adverse effects from anticholinergic medications?
Blurred vision Dry eyes Dry mouth Drowsiness Confusion Hallucinations Tachycardia Urinary retention Constipation Flushing Anhidrosis
79
What psychiatric medications are more likely to cause hyponatraemia?
SSRIs carbamazepine Less likely TCAs, mirtazapine
80
What antipsychotic generally has fewest side effects?
Aripiprazole
81
82
What two antipsychotics are less likely to cause or aggravate Parkinsonism?
Clozapine Quetiapine
83
What two antipsychotics tend to cause more weight gain / metabolic side effects?
Clozapine Olanzapine
84
What medications are typically implicated in Neuroleptic Malignant Syndrome?
Antipsychotics
85
What are the cardinal signs of neuroleptic malignant syndrome?
Fever Autonomic instability Rigidity Mental status changes Elevated CK elevated WCC However no sign is pathognomonic and some px may not be experience full suite of signs (particularly if second gen antipsychotic)
86
How do you manage neuroleptic malignant syndrome?
Stop causative agent Supportive care eg fluids Muscle relaxants (eg dantrolene) and dopamine agonists (amantadine) if severe
87
What is the usual cause of serotonin toxicity?
Combining different agents that increase serotonin eg SSRIs, TCa, SNRI, opioids, antihistamines, amphetamines, cocaine, MAOIs, St. John’s wort, LSD, triptana
88
What are the typical features of serotonin syndrome?
Changes in mental state Autonomic incl hyperthermia, shivering, mydriasis Neurological incl myoclonus, clonus, hyperreflexia
89
What psychiatric meds are more likely to cause QTc prolongation?
Escitalopram Citalopram Quetiapine Ziprasidone
90
What are the short term effects of hyperprolactinaemia?
Hypogonadism Sexual dysfunction Galactorrhoea Gynecomastia Altered menstrual cycle
91
What are the long term effects of hyperprolactinaemia?
Weight gain Osteoporosis Increased risk of breast, prostate and pituitary cancer, Depression cVD
92
What psych meds are most likely to cause hyperprolactinaemia?
First Gen antipsychotics eg haloperidol Occ second gen antipsychotics eg risperidone, paliperidone Very occ SSRIs
93
What is the management of hyperprolactinaemia caused by antipsychotic medications?
Switch to aripiprazole (D2 partial agonist) or cautious use of adjunctive dopamine agents (eg bromocriptine, amantadine, pramipexole)
94
What are side effects of Lithium?
Hypercalcaemia Hyperparathyroidism Hypothyroidism Renal disease - nephrogenic diabetes insipidus - nephrotic syndrome - renal tubular acidosis - glomerulosclerosis
95
What signs may indicate lithium toxicity?
Confusion GI distress Coarse tremor Sick sinus syndrome Heart block Reversible T wave changes Very rarely - pseudotumour cerebri
96
What side effect of Clozapine is most likely to be fatal?
Constipation
97
What are the key side effects of Clozapine?
Constipation Agranulocytosis Myocarditis - first 2 months Cardiomyopathy - beyond 3 mths Drilling Seizures Enuresis
98
What side effects may antiepileptic mood stabilisers have?
Osteoporosis PCOS (Valproate) Hyperammonia (Valproate, Carbamazepine) Leukopenia and thrombocytopenia (Valproate, Carbamazepine) Hypersensitivity reactions or DRESS Movement disorders
99
What are examples of CYP450 inducers?
Carbamazepine St. John’s wort Rifampicin Phenytoin Tobacco Some steroids
100
What psychiatric drugs are excreted renally and therefore need to be used cautiously in renal impairment?
Lithium Gabapentin/pregabalin Topiramate Paliperidone
101
What psychiatric drug is particularly implicated in causing Drug Induced Liver Injury?
Duloxetine
102
What psychiatric medications are contraindicated in someone with hepatitis?
Valproate Carbamazepine
103
What psychiatric meds are contraindicated in patients with neutropenia?
Carbamazepine Clozapine
104
What psychiatric drugs are contraindicated in patients with epilepsy?
Bupropion Clozapine
105
What are the key teratogenic risks of valproate?
Neural tube defects 6% Vit K def with third trimester exposure (resulting in preterm labour and bleeding risk)
106
Which medical conditions are assoc with high risk of suicide?
Huntingtons Multiple sclerosis Epilepsy HIV Malignancy
107
What is AIDS-assoc Kaposi Sarcoma?
A low-grade vascular tumor associated with infection with human herpesvirus 8 (HHV-8), also known as the KS-associated herpesvirus (KSHV). variable clinical course, ranging from minimal disease presenting as an incidental finding to a rapidly progressing neoplasm that can result in significant morbidity and mortality, depending upon the specific sites of involvement
108
How do you treat AIDs-assoc Kaposi sarcoma?
ART + Consider local therapies including Intralesional chemo Radiotherapy Topical imiquimod Cryotherapy Or if advanced/rapidly progressive KS then systemic therapy with doxorubucin
109
What is the most important mediator of keratinocyte death in SJS/TEN?
Granulysin
110

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