Fungal and Skin Infections & Leprosy Flashcards
1
Q
- What is this?
- What is characteristic of appearance?
- Differential diagnosis?
- Organism?
- Geography?
- Risk factors?
- How to confirm dx?
- Treatment?
A
- Sporotrichosis
- characteristic lesions along line of lymphatics, “skip lesions”
- may also occur on face
- sporotrichoid spread of Cutaneous leishmaniasis can have similar appearance
- Sporothrix schenckii
- most common in Central and South America
- risk factors: gardeners, farm workers, timber workers, HIV +ve, cat owners (cats lesions may team with the organism)
- confirm by histology or culture
- tx itraconzole or KI solution orally
- disseminated disease rare, requires amphotericin
2
Q
- What is this?
- Where geographically?
- Organism? Where from?
- How does it present?
- Complications?
- Differential Diagnosis?
- How confirm diagnosis?
- How treated?
A
- Mycetoma
- Subcut fungal infection common in many areas of tropics and subtropics esp Sudan and India
- soil organisms
- actinomycetes
- Nocardia, streptomyces somaliensis, Actinomadura
- Fungi
- Madurella mycetomatis and grisea, Leptosphaeria senegalensis
- actinomycetes
- presents as painless draining sinus, extrusion of granules or grains
- enlarges slowly, spreads to skin, subcut tissue, bone
- usually no associated nodes
- classical radiological changes
- Differential dx:
- chronic osteomyelitis, TB, Kaposi’s
- Dx
- microscopy of crushed grains, culture, histology
- Tx
- Eumycetoma (fungus): Itraconazole 400 mg od x 1-2 yrs, surgery
- Actinomycetoma (bacterium): co-trimoxazole + streptomycin or amikacin x sev weeks
- amoxyclavulin may be effective
3
Q
What are the two clinical forms of Histoplasmosis?
Where found?
Relationship to HIV?
A
-
Classical: Histoplasma capsulatum var capsulatum
- North and latin america, esp Ohio River Valley, also East and South Africa
-
African: H. capsulatum var duboisii,
- primarily rain forest region of West Africa
- well recognized complication of HIV in N. America, growing evidence of considerable burden in S. America, leading cause of death in French Guiana
- may be underdiagnosed, misdiagnosed as TB
4
Q
What is the clinical picture with Classical Histoplasmosis?
What is the organism?
risk factors
treatment
A
- H. capsulatum var capsulatum
- acute histoplasmosis may be self limited mild illness
- chronic pulmonary histo affects those with damaged lungs and may be picked up incidentally on cxr
- may mimic TB: progressive pneumonia, night sweats, apical lung infiltrates and cavitation
- disseminated disease with impaired T cell fx, esp HIV
- fever, wt loss, skin lesions (below), mucosal ulcers, hepatosplenomegaly
- other risk factors:
- exposure to bat or bird droppings
- elderly, chronic steroid use
- Tx: Itraconazole doc, Keto or fluconazole may do
- Amphotericin for severe disease, liposomal ampho better
Tx duration 6 weeks for African, up to 6 months for classical
5
Q
- What is African Histoplasmosis?
- where found, what organism
- Clinical forms and description of each
- How diagnosed?
A
- Primarily found in West Africa
- Histoplasma var. duboisii
- no clear correlation with HIV, but increasingly recognized, prev confused with TB
- Localised form
- Skin and subcut granulomas:
- tender nodules, chronic ulceran and eczematous or psoriaform lesions
- Bone infection: multiple osteolytic lesions in soft bones
- Sinus tracts may drain through skin
- Skin and subcut granulomas:
- Disseminated disease
- fever, anemia, lymph nodes, liver, spleen, bowel
- lung involvement rare
- Dx: microscopy or culture of orgs in body fluid or tissue (buffy coat, marrow aspirate or liver biopsy if disseminated
- serology if immunocompetent
- Ag detection useful for HIV (serum or urine) but limited availability
- Tx: Itraconazole doc, Keto or fluconazole may do
- Amphotericin for severe disease, liposomal ampho better
- Tx duration 6 weeks for African, up to 6 months for classical
6
Q
- What is Paracoccidoidomycosis?
- AKA?
- Where found
- Clinical syndromes?
- Diagnosis?
- Treatment? For how long?
A
- aka South American Blastomycosis in Central & South America
- granulomatous disease prob acquired by inhalation
- like TB subclinical infection may reactivate later in life
- 2 main clinical syndromes
-
Disseminated disease: under 30, skin and mucosal lesions
- spleen, liver, bone marrow, lymph nodes, adrenals may all be involved
-
Chronic form: primarily progressive pulmonary illness
- tends to involve mid or basal zones
-
Disseminated disease: under 30, skin and mucosal lesions
- Dx by demonstrating fungal elements or culture sputum.
- important to differentiate histoplasmoiss
- tx sulphadiazine or co-trimoxaozole, itraconazole or amphoteracin
- long term 6-18 months
7
Q
- South America. What is this?
- Differential?
- What would typical xray findings of this disease be in chronic pulmonary disease with same organism?
A
- blastomycosis
- ddx:
- Yaws (but not yaws in South America, only Pinto)
- Mucocutaneous leishmaniasis
- malignancy
- syphilis
- progressive pulmonary illness tends to involve mid or basal zones (image)
8
Q
- What fungus might cause these skin lesion in SE Asia?
- what are the characteristic appearances?
- What associated system involvement?
- How diagnosed?
- Important differential?
A
-
Penicillium marnefii
- important pathogen in AIDS patients in SE Asia (3rd most common)
- affects those with advanced HIV disease (note picture was from AIDS Hospice)
- classically diffuse papular skin lesions tih central necrosis
- may look like molluscum
- may have oropharyngeal involvement
- may be chronic with wt loss, fever, malaise, anemia, lymphadenopathy and hepatomegaly
- resp involvement with abnormal cxr
- Dx by isolating org from blood, lymph nodes, bone marrow
- dx from Histoplasma
- Tx amphotericin, flucytosine, azoles
- high relapse rate in AIDS, may need secondary prophylaxis
9
Q
- Whats the diagnosis?
- Which patients?
- Associated findings?
A
- Candidal esophagitis
- important pathogen in HIV +ve patients
- associated with oropharyngeal candidiasis or disseminated candidiasis (liver, spleen, skin, multiorgan)
- tx azoles or amphotericin
10
Q
What is first line therapy for most severe systemic fungal infections?
Exception?
Toxicities?
How minimized?
A
- amphotericin first line therapy for most severe fungal infections
- may not be effective against aspergillus
- Toxicities
- rigors prevented with steroids
- renal impairment: minimized with pre-hydration with 1 l ns & 20 mmol KCl IV over 2-4 hrs berfore effusion
- oral K bid
- check K, Cr at baseline and twice a week
- Liposomal formulations less toxic but v. expensive
11
Q
- which for
- superficial infections
- cryptococcus
- candida
- aspergillus
- sporotrichosis
- blastomycosis
- histoplasmosis
A
- ketoconazole for superficial infections, less active in systemic infections
- fluconazole doc for cryptococcal disease, candida
- itraconazole more effective for aspergillus, sporotrichosis, blastomycosis, histoplasmosis
12
Q
- What is the commonest form of meningitis in HIV +ve patients in sub-Saharan Africa?
- What is the classical recommended treatment for this infection?
- What is the survival rate given this treatment?
- What are the problems with this approach in resource poor settings?
- Based on recent studies with survival rates with abbreviated amphotericin regimens what are the new WHO recommendations for treatment of cryptococcal meningitis?
A
- Commonest form of meningitis in sSA: cryptococcal meningitis
- Tx
- (Amphotericin B 1 mg/kg + flucytosine) x 2 weeks
- fluconazole 800 mg daily x 8-10 wks
- 10 wk survival 50-80%
- flucytosine expensive and often unavailable
- New WHO recommendations
- Preferred: (Ampho B 1 mg/kg + flucytosine 100 mg/kg/day in 4 doses) x 1 wk
- then 1 wk of fluconazole 1200 mg/day
- Alternative: (fluconazole 1200 mg daily + flucytosine) x 2 weeks
- Alternative: (Ampho B + fluconazole) x 2 weeks
- All regimens to be followed by 8 wks of 800 mg daily fluconazole
- secondary prophylaxis min 1 yr until stable on ART and evidence of immune reconstitution
- Preferred: (Ampho B 1 mg/kg + flucytosine 100 mg/kg/day in 4 doses) x 1 wk
13
Q
- Is dexamethasone recommended as an adjunct to treatment of cryptococcal meningitis.
- Why or why not?
A
- NO!
- It reduces survival and increases disability (NEJM 2016 Feb 11; 374 (6): 542-54
14
Q
- Should ARV’s be started early or late when treating patients newly dx’d with cryptococcal meningitis and found to be HIV+ve.
- Should steroids be used as adjunctive treatment?
A
- As with TB, initiation of ARV should wait until treatment of Cryptococcal meningitis is well established or done (5-10 wks)
- In 2 trials comparing early with late ARV initiation the early treatment arms had to be suspended because of increased mortality with early treatment
- Steroids should NOT be used
- presumably due to lack of inflammatory response in CSF in those treated with steroids, a trial (2016 NEJM) comparing tx +/- dexamethasone was stopped early because of excess mortality in treatment arm.
15
Q
- In what proportion of pts with CD4<100 is CrAg positive?
- What implications for mortality?
- How should this be managed?
A
- 6-13% of HIV+ve pts with CD4<100 have assymptomatic cryptococcemia
- much higher mortality if CrAg +ve (HR 2.57)
- recommend treat with azoles and start ART when available
16
Q
What is this?
A
- Ecthyma is a skin infection characterised by crusted sores beneath which ulcers form. It is a deep form of impetigo, as the same bacteria causing the infection are involved. Ecthyma causes deeper erosions of the skin into the dermis.
Streptococcus pyogenes and/or Staphylococcus aureus are the bacteria responsible for ecthyma.
17
Q
- Cardinal Signs of Leprosy
A
WHO definition. In endemic area need one of:
- Definite loss of sensation in a skin lesion consistent with leprosy
- Skin smears positive for acid fast bacilli
- Thickening of one or more peripheral nerves
18
Q
Presentation of Leprosy
A
- •Skin lesion
- –Erythematous
- –Plaque like
- •Nerve damage
- –Hands, feet, due to peripheral nerve injury
- •Foot drop, hand weakness
- –Injury in anaesthetic skin
- •Reaction
- –Skin lesion oedema
- –Peripheral nerve injury
19
Q
What is lagopthalmos?
A
- Inability to close eyes
- Please note that the word “lagophthalmos” has an interesting etymological history. The word is unrelated to lag as in lid-lag. It is derived from the Greek lagos meaning hare and ophthalmos meaning eye. Supposedly, the hare sleeps with its eyes open.
20
Q
What is this?
Define.
A
- Tuberculoid leprosy is a form of leprosy characterized by solitary skin lesions that are asymmetrically distributed with few lesions and well demarcated edges.
21
Q
What is this?
A
- Lepromatous Leprosy (LL) Due to an absence of cell-mediated immunity inlepromatous leprosy, M. leprae proliferates freely and this results in widespread systemic disease. The initial skin lesions are erythematous or hypopigmented disseminated, small macules that have poorly defined borders.
22
Q
What is the Ridley-Jopling Classification of leprosy?
A
- A classification based on the kind and number of lesions and presence of nerve damage. Based on a gradation of anergy and progression of disease.
- T = Tuberculous
- B = Borderline
- L = Lepromatous
- Has been supplanted by WHO classification of
- Paucibacillary (up to 5 skin Lesion)
- Multibacillary (>5 lesions)
23
Q
What is the disease spectrum of Leprosy?
Why does it matter?
A
- Borderline disease is unstable
- BT disease is associated with sever large nerve damage
- LL/BL ptatiens suffer ENL (Erythema Nodosum Leprosum) reactions
24
Q
What is this?
Why is it important?
A
- a thickened nerve
- one of the cardinal signs of leprosy
25
Q
What are skin slits and when are they used for diagnosis?
A
- Z-N stain
- suspected lesions and sites commonly affected by lepromatous leprosy (forehead, eyebrows, earlobes) are sampled
- read on log scale 0 to 6+
- useful in lepromatous cases and unusual skin lesions
- can start treatment where clear-cut skin and/or nerve lesions are present before slit skin smear results are available.
26
Q
What is the differential dx for an erythematous macule suspected to be leprosy?
A
- macule
- fixed drug eruption
- pityriasis rosea
- tinea corporis
- erythema multiforme
27
Q
Diff dx for hypopigmented lesion suspected to be leprosy?
A
- hypopigmented
- vitiligo
- post-inflammatory lesions
- Early PKDL
29
Q
What is this?
A
- Granuloma multiforme (also known as “Mkar disease” and “granuloma multiforme (Leiker)”) is a cutaneous condition most commonly seen in central Africa, and rarely elsewhere, characterized by skin lesions that are on the upper trunk and arms in sun-exposed areas.
40
Q
What is this?
how is it treated?
A
- a Type 1 skin reaction in a pt with leprosy after starting treatment
- increase redness and edema
- Steroids
–Prednisolone 40mg/day
–reduce by 5mg/day every month
Continue regular neurological assessment
43
Q
What are Type 2 reactions in leprosy?
Who is at risk?
What is the underlying pathology/immunology?
A
- Erythema Nodosum Leprosum
- systemic reactions with
- pain
- skin lesions
- malaise and fever
- neuritis
- iritis
- other: orchitis, arthritis, lymphadenopathy, renal disease
- At risk: LL (50%) and BL (15%)
- Pathophysiology
- immune complex deposition
- T cell dysregulation
- overproduction of TNF
44
Q
What are these?
What are the aims of treatment for this condition and associated conditions?
A
- ENL (Erythema Nodosum Leprosum) dactylitis and skin changes
- Treatment Goals
- control pain and inflammation
- control acute neuritis
- halt eye damage
- reassure the patient
- continue anti-leprosy drugs
46
Q
Describe the geography of leprosy:
Where?
How many new cases a year?
A
- 83% of worlds registered cases in 6 countries: India, Brazil, Indonesia, Tanzania, Ethiopia, Uganda but
- 22 global priority countries (see map)
- new cases stable since 2007
- 214,000 per year
