Transcript General Data

Medicine II
Infectious Diseases
BGD 1
Subsection B1
1
• E.M.
– 42 years old, female, single
– Filipino, Roman Catholic
– San Pablo City, Laguna
– Date of admission: 11/18/09
– Informant: patient
– Reliability: 85%
2
Chief Complaint:
non-healing ulcer on the left leg
3
History of Present Illness
•Pain, swelling over the area of the right
Achilles tendon
•Consult: San Pablo Medical Center
•Ancillary: X-ray of the right leg – normal
•Management: unrecalled patch medications
which provided relief of the pain, but
persistence of the swelling
4
History
ofPresent
Present
Illness
History of
Illness
•persistence of the swelling
•Consult to a “manghihilot”
•Massage therapy was done
•undocumented fever temporarily relieved by
intake of Paracetamol 500mg tab
5
History of Present Illness
• persistence of the swelling and fever
•Confined at San Pablo Medical Center
•Assessment: abscess of the right foot
•Patient was given unrecalled antibiotics.
•Discharged with cast applied over the right leg
6
History of Present Illness
•After 7 days, patient noted heaviness of the right leg with
pus dripping from the cast
•Consult - Removal of the cast
•Multiple ulcers on the right leg
•Wound debridement was done.
•Increase depth of the ulcer, skin graft from right thigh was
harvested and was place over the area
•Wound had good coaptation and was completely healed
7
History of Present Illness
3 1/2 years PTA
•patient noted appearance of the same lesions
over the of the wound
•Consult: Philippine General Hospital
•Biopsy:TB of the skin
•Medications: Anti-TB for 6 months
•After the therapy, the wound was noted to be
completely healed.
8
History of Present Illness
2 1/2 years PTA
•patient noted recurrence
•Consult: RITM
•Assessment: TB of the skin
•Advised transfer to another hospital
•San Pablo Medical Center
•Above the knee amputation of the right leg
with skin graft from the left thigh was done.
9
History
of
Present
Illness
History of Present Illness
2 years PTA
•New ulcer was noted on the medial aspect
and dorsum of the left leg and right forearm
•Advised cleansing with bleach
•Healing of the wound with granulation tissue.
10
History ofofPresent
Illness
History
Present
Illness
1 1/2 months PTA
•Painful nodules on the anterior aspect of the left leg 
erythematous patch  several moist ulcers over the
dorsum and medial aspect of the left leg
•Cleanse with bleach and would heal with granulation
tissue.
•Consult: PGH
•Ancillary: Venous duplex scan was requested – normal
results
•Assessment: not disclosed.
11
History
of
Present
Illness
History of Present Illness
18 days PTA
•Recurrence of several painful nodules grade
8/10 on the anterior leg  erythematous patch
 ulcers that coalesce with necrotic tissues
and oozing with blood eventually affecting the
posterior aspect of the left leg.
•self-medicated with Tramadol, Biogesic and
Diclofenac which provided temporary relief of
the pain
12
History
of
Present
Illness
History of Present Illness
3 days PTA
•rapid increase in size of the wound
•increase in the severity of the pain now grade
10/10
ADMISSION
13
Review of Systems
• General: (-) weight loss (-) fever, (-) excessive sweating,
(-) weakness, (-) easy fatigability, (-) insomnia
• Skin: (-) itchiness, no photosensitivity, (-) hair changes
• Eyes: (-) blurring of vision, (-) itchiness, (-) pain
• Ear: (-) deafness, (-) discharge, (-) tinnitus
• Nose: (-) epistaxis, (-) colds, (-) discharge
• Throat: (-) soreness, (-) tonsillitis
• Mouth: (-) sores, (-) fissures, (-) bleeding gums
• Neck: (-) stiffness, (-) limitation of movement, (-) masses
• Vascular: (-) intermittent claudication
14
Review of Systems
• Pulmonary: (-)dyspnea , (-) no cough, (-) hemoptysis
• Cardiac: (-) chest pains,(-) palpitations, (-) PND,
• Gastrointestinal: (-) diarrhea, (-) constipation (-) change in
bowel movements
• Genitourinary: (-) frequency, (-) flank pain, (-) gross
hematuria
• Muscular: (-) joint swelling, (-) bone pains
• Endocrine: (-) nocturia, (-) polydipsia, (-) polyphagia, (-)
polyuria (-) paresthesia, (-) heat-cold intolerance
• Hematopoetic: (-) abnormal bleeding (-) easy bruisibility
• Neurologic: (-) seizures
• Psychiatric: (-) anxiety, (-) depression, (-) interpersonal
15
relationship difficulties
Past Medical History
• (+) Blood transfusion, number of units
unrecalled when the patient underwent above
the knee amputation (2007)
• (-) Hypertension
• (-) allergies
• (-) asthma
• (-) thyroid diseases
• (-) DM
• (-) skin disease
16
OB History
• nulligravid
17
Menstrual History
•
•
•
•
•
M- 13 years old
I-28- 30 days
D- 3 days
A-2 ppd moderately soaked
S- dysmenorrhea Day 1
18
Sexual History
• the patient denies any sexual contact
19
Personal & Social History
• Non-smoker
• Non-alcoholic beverage drinker
• No diet preferences
20
Family History
•
•
•
•
•
•
•
•
(+) CVD mother, died at 76 years old
(+) sibling MI
(-) skin disease
(-) DM
(-) asthma
(-) allergies
(-) thyroid diseases
(-) autoimmune disorders
21
Physical Examination
• Conscious, coherent, ill-looking, wheel chair borne
not in cardiorespiratory distress
• BP: 120/80mmHg on both upper extremities and
left lower extremity, PR 100 bpm, full, regular, RR
20 cpm, regular, T=37.0°C
• Wt 120lbs (54.54 kg) Ht 5’2 (157.48cm)
22
BMI 22
• (+) well defined ulcer on the entire left leg with purplish irregular border topped with
bleeding necrotic tissue with slightly violaceous plaque topped with multiple punch out
ulcer some with crusts on the right forearm, dorsum and medial aspect of left foot and
right AKA stump, (+) scars over the right and left thigh.
23
Physical Examination
• Pale palpebral conjunctiva, anicteric sclera
• Moist buccal mucosa, no oral ulcers, anicteric
frenulum lingua.
• Neck is not rigid, thyroid gland is not enlarged, no
palpable cervical lymph nodes
• Symmetrical chest expansion, no retractions,
resonant on percussion, no crackles, clear breath
sounds unimpaired vocal and tactile fremitii
24
Physical Examination
• Adynamic precordium, AB at 5th LICS AAL, s1>s2
at the apex, s1<s2 at the base, no heaves, no lifts,
no thrills, no murmurs
• Flabby abdomen, normoactive bowel sounds, liver
span 9cm MCL, tympanitic on percussion, soft, no
mass, no tenderness, no murphy’s sign
• Pulses full and equal, no cyanosis, no edema
25
Neurologic Examination
•
•
– (+) gag reflex
Conscious, coherent, oriented– can shrug shoulders
to three spheres, GCS 15
– turns head side to side against
resistance
Cranial Nerves:
• tongue midline on protrusion
– pupils 2-3mm ERTL
– (+) corneal reflex
– (+) ROR, clear disc margins, no
visual field cuts
– EOM full and equal
– V1V2V3 intact
– no ptosis
– can smile, can raise eye brows,
can puff cheeks
– gross hearing intact
– uvula midline on phonation
• Motor: MMT 5/5 on the LLE
and UE
• Sensory: no sensory deficits
• DTR’s: +2 on LLE, and UE.
• No Babinski
• No nuchal rigidity
26
SALIENT FEATURES
Subjective
• Nulligravid
• Non-healing rapidly
progressing ulcer on the
left foot
• Not known diabetic
• (-) polyuria, polyphagia,
nocturia, no weight loss
• Non-smoker
• (-) changes in bowel
movement
• (-) joint pains, (-) morning
stiffness
• (+) above the knee
amputation right lower
extremity
Objective
• 42 y/o, Female
• BP 120/80mmHg on both upper
extremities and left extremity, PR
100 bpm, full, regular, RR 20 cpm,
regular, T=37.0°C
• Warm dry skin, (+) well defined
ulcer on the entire left leg with
purplish irregular border topped
with bleeding necrotic tissue with
slightly violaceous plaque topped
with multiple punch out ulcer
some with crusts on the right
forearm, dorsum and medial
aspect of left foot and right AKA
stump, (+) scars over the right
and left thigh.
• Pale palpebral conjunctiva,
Pulses full and equal, no
cyanosis, no edema
27
Assessment
28
Differential Diagnosis
29
Cutaneous Tuberculosis
Cutaneous Tuberculosis
- extrapulmonary manifestation of TB
- caused by:
Mycobacterium Tuberculosis
Mycobacterium Bovis
- its development requires a degree of
immunity impairment of the host
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Morphological Manifestations
• Granulomatous inflammation
• Variable necrosis
• Variable vasculitis
Demonstration of M. tuberculosis via:
1.
2.
3.
Culture
Staining
PCR
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Classification
Tuberculous Chancre
Tuberculosis Verrucosa Cutis
Lupus Vulgaris
Scrofuloderma
Orificial Tuberculosis
Miliary Tuberculosis
Metastatic Tuberculosis Abscess
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Most plausible type for differential
diagnosis based on course and features
of the lesion:
Tuberculous Chancre
Lupus Vulgaris, ulcerative type
Scrofuloderma
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Tuberculous Chancre
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Lupus Vulgaris
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
Scrofuloderma
Cutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328
1175-0561/02/0005-0319/$25.00/0
Cutaneous Tuberculosis
But due to the presence of pain on the
initiation and course of the lesion
Tuberculous Chancre is ruled out.
Further exclusion of Lupus Vulgaris ulcerative
type and Scrofuloderma necessitates
laboratory investigation.
Necrotizing fasciitis
• Rapidly spreading destructive disease of the
fascia.
• Deep-seated infection of the subcutaneous
tissue that progressively destroys fascia and
fat but may spare the skin and muscle
• Usually attributable to Group A Streptococci
• Other etiologies: Mixed aerobe and anaerobe
(Clostridium perfringens, Peptostreptococcus,
Burkholderia and Bacteroides spp.)
• Risk factors: Surgeries, Diabetes, Peripheral
vascular disease
Harrison's Principles of Internal
Medicine, 17th ed.
Necrotizing fasciitis
• 61-year-old Chinese man with a history of psoriasis
and alcoholic liver cirrhosis sought treatment for left
ankle swelling, erythema, and tenderness
• could not recall any antecedent trauma to the
affected limb
• Febrile
• Progression to formation of blisters, extensive
subcutaneous tissue and fascial necrosis, loss of
resistance of the normally adherent superficial fascia
to blunt dissection, and foul-smelling “dishwater” pus
Necrotizing fasciitis
• Culture: Burkholderia pseudomallei.
(Endemic to Southeast Asia, Taiwan,
China, Central and South America, and
northern Australia)
• sporadic infections occur throughout
the world
Yi-Shi Wang, Chin-Ho Wong, and Asok Kurup. Cutaneous
Melioidosis and Necrotizing Fasciitis Caused by Burkholderia
pseudomallei. 2003
Necrotizing fasciitis
(Group A Streptococci)
A. Definite case
1. Necrosis of soft tissues with involvement of the
fascia
PLUS
2. Serious systemic disease, including one or
more of the following:
a) Death
b) Shock (systolic blood pressure <90 mm of
Hg).
c) Disseminated intravascular coagulopathy
Necrotizing fasciitis
d) Failure of organ systems
a. respiratory failure
b. liver failure
c. renal failure
3. Isolation of group A Streptococcus
from a normally sterile body site
Necrotizing fasciitis
B. Suspected case
1 . 1 + 2 and serologic confirmation of
group A streptococcal infection by a 4fold rise against:
a) streptolysin O
b) DNase B
2. 1 + 2 and histologic confirmation:
Gram-positive cocci in a necrotic soft
tissue infection
Usual Clinical Course
• 24 hours of the initial lesion— mild erythema,
swelling, heat
• Next 24 to 48 hours-the erythema changed
from red to purple and then to blue, and
blisters and bullae, which contained clear
yellow fluid
• Days 4 and 5- the purple areas became
gangrenous.
• Day 7 to day 10- the line of demarcation
became sharply defined, and the dead skin
began to separate at the margins or breaks in
the center, revealing an extensive necrosis of
the subcutaneous tissue.
Necrotizing fasciitis
• More severe cases: the process advanced
rapidly until several large areas of skin
became
gangrenous, and the intoxication rendered
the patient dull, unresponsive, mentally
cloudy, or even delirious.
Streptococcal Toxic-Shock Syndrome:Spectrum of Disease,
Pathogenesis, and New Concepts in Treatment
Dennis L. Stevens, Ph.D., M.D.
Emerging infectious Diseases Vol.1 No.3 July-Sept 1995
Necrotizing Fasciitis
Necrosis of tissue and fascia
Rapidly Progressive course
Shock, DIC, Organ system Failure
Isolation of causative agent in the site
Pyoderma
gangrenosum
Pyoderma Gangrenosum
• poorly understood
• In 50 to 70% of the patients, PG is
associated with underlying systemic
diseases such as inflammatory bowel
disease, myeloproliferative disorders,
hematological or malignancies
49
Primary or Secondary?
50
SYSTEMIC LUPUS
ERYTHEMATOSUS
Table 313-3. Diagnostic Criteria for Systemic Lupus Erythematosus
•
•
•
•
•
•
•
•
•
•
•
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis (nonerosive arthritis of two or more peripheral joints, with tenderness,
swelling, or effusion)
Serositis (pleuritis or pericarditis)
Renal disorder (proteinuria >0.5 g/d or > or = 3+, or cellular casts)
Neurologic disorder (seizures or psychosis without other causes)
Hematologic disorder (hemolytic anemia or leukopenia (<4000/µL) or
lymphopenia (<1500/µL) or thrombocytopenia (<100,000/µL) in the absence of
offending drugs)
Immunologic disorder (Anti-dsDNA, anti-Sm, and/or anti-phospholipid)
Antinuclear antibodies
*If > or = 4 of these criteria are present at any time in a patient’s history, the
diagnosis is likely to be SLE. Specificity is ~95%; sensitivity is ~ 75%.
NOTE: Our patient did not have any of the above mentioned signs and
symptoms; therefore, not fulfilling the diagnostic criteria for SLE.
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., p. 2077
Cutaneous Manifestations of Lupus
Erythematosus
A. Acute
B. Subacute
C. Chronic
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., pp. 316-317
Acute Cutaneous LE
• characterized by erythema of the nose and malar
eminences in a “butterfly” distribution
• erythema is often sudden in onset, accompanied by
edema and fine scale, and correlated with systemic
involvement
• There may be widespread involvement of the face as well
as erythema and scaling of the extensor surfaces of the
extremities and upper chest.
*Skin biopsy of acute lesions may show sparse dermal
infiltrate of mononuclear cells and dermal edema. There
may be cellular infiltrates around blood vessels and hair
follicles are notable (hydropic degeneration of basal cells
of the epidermis).
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., pp. 316-317
Subacute cutaneous lupus
erythematosus (SCLE)
• Characterized by a widespread photosensitive, nonscarring
eruption
• may present as a papulosquamous eruption that resembles
psoriasis or annular lesions that resemble those seen in
erythema multiforme.
• The papulosquamous form are discrete erythematous papules
that arise on the back, chest, shoulders, extensor surfaces of
the arms, and the dorsum of the hands;
• lesions are uncommon on the face, flexor surfaces of the
arms, and below the waist.
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., pp. 316-317
Subacute cutaneous lupus
erythematosus (SCLE)
• Skin biopsy reveals a dense mononuclear cell
infiltrate around hair follicles and blood vessels
in the superficial dermis, combined with hydropic
degeneration of basal cells in the epidermis.
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., pp. 316-317
Discoid lupus erythematosus
(DLE)
• is characterized by discrete lesions, most often on the face,
scalp, or external ears.
• The lesions are erythematous papules or plaques with a thick,
adherent scale that occludes hair follicles (follicular plugging).
• When the scale is removed, its underside will show small
excrescences that correlate with the openings of hair follicles
and is termed a “carpet tack” appearance.
• Biopsy of DLE lesions shows hyperkeratosis, follicular plugging,
and atrophy of the epidermis; hydropic degeneration of basal
keratinocytes; and a mononuclear cell infiltrate adjacent to
epidermal, adnexal, and microvascular basement membranes.
Braunwald et al, Harrison’s Principles of Internal Medicine, 17th Ed., pp. 316-317
Antiphospholipid syndrome
Antiphospholipid antibodies syndrome
• a condition that can cause clotting
within your arteries or veins and various
other problems, some life-threatening
• immune system mistakenly produces
antibodies to certain proteins in your
blood that normally attack body
invaders, such as viruses and bacteria
http://www.mayoclinic.com/health/
antiphospholipidsyndrome/DS00921
Criteria
•
The diagnosis of APS is made in case of a clinical event (vascular thrombosis or pregnancy event) and
repeated positive tests of aPL performed 12 weeks apart (repeat aPL testing is necessary due to the
naturally occurring presence of transient low levels of aPL following infections).
•
The Updated Sapporo APS Classification Criteria (1998, published in 1999) are commonly used for APS
diagnosis.Based on these criteria, APS diagnosis requires:
•
a) Vascular Thrombosis (blood clots) in any organ or tissue or Pregnancy Event (one or more
miscarriages after 10th week of gestation, three or more miscarriages before 10th week of gestation, or
one or more premature births before 34th week of gestation due to eclampsia) and
•
b) Persistently (6 weeks apart) Positive aPL (lupus anticoagulant test, moderate-to-high titer
anticardiolipin antibodies, or moderate-to-high titer β2-glycoprotein-I antibodies).
•
The International Consensus Statement is commonly used for Catastrophic APS diagnosis. Based on this
statement, Definite CAPS diagnosis requires:
•
a) Vascular Thrombosis in three or more organs or tissues and
•
b) Development of manifestations simultaneously or in less than a week 'and
•
c) Evidence of small vessel thrombosis in at least one organ or tissue and
•
d) Laboratory confirmation of the presence of aPL.
•
Some serological tests for syphilis may be positive in aPL-positive patients (aPL bind to the lipids in the
test and make it come out positive) although the more specific tests for syphilis that use recombinant
antigens will be negative.
* the patient did not have any of the above mentioned, therefore she did not
fulfill the criteria for the diagnosis of APS
Antiphospholipid syndrome
infection
primary
secondary
no other
autoimmune
disorder
w/lupus or other
autoimmune
disorder
medication
genetic
predisposition
http://www.mayoclinic.com/health/antiphospholipidsyndrome/DS00921/DSECTION=causes
SLE
• the diagnosis has to be established by clinical
features as histologic alterations are unspecific
and characteristic serologic or hematologic
markers do not exist
• about 40% of patients with SLE have high
levels of antiphospholipid antibodies such as
lupus anticoagulant (LA) and cardiolipin
antibodies
• about half of these patients develop a
secondary antiphospholipid syndrome
• skin manifestations such as ulcers with
antiphospholipid syndrome are a well known
and typical epiphenomenon
http://www.john-libbey-eurotext.fr/en/revues/medecine/ejd/e-docs/00/01/88/57/article.md
Crohn’s disease
IDIOPATHIC INFLAMMATORY BOWEL
DISEASE
- The illnesses in this category, which
include Crohn’s disease and chronic
ulcerative colitis, are among the most
common organic causes of chronic
diarrhea in adults and range in severity
from mild to fulminant and life-threatening.
They may be associated with uveitis,
polyarthralgias, cholestatic liver disease
(primary sclerosing cholangitis), and
various skin lesions (erythema nodosum,
pyoderma gangrenosum)
• There are many complications that can
occur with Inflammatory Bowel Disease
(IBD) including arthritis, liver disease,
nutritional disorders, anemia, and skin
disorders. Skin disorders are a fairly
common problem, and may affect up to
25 percent of people who suffer from
IBD. One type of skin disorder that may
occur in IBD is pyoderma
gangrenosum.
Crohn’s disease
• Lab abnormalities: elevated ESR and CRP
• In more severe cases: hypoalbuminemia, anemia, and
leukocytosis
• Endoscopic feature: rectal sparing, aphthous ulceration, fistulas,
and skip lesions, continuous disease, “Cobblestoning,
granuloma on biopsy
• Clinical: gross blood in stool, mucus, systemic symptoms, pain,
abdominal mass, significant perineal disease, fistulas, smallintestine obstruction, colonic obstruction, response to antibiotics,
recurrence after surgery, ANCA-positive, ASCA-positive
• Radiographic: small bowel significantly abnormal, abnormal
terminal ileum, segmental colitis, asymmetric colitis, stricture
*the patient did not have any of the signs and symptoms
mentioned above and therefore does not have Crohn’s disease
Primary Pyoderma
gangrenosum
Diagnosis Criteria
?
?
?
Patient still awaiting
biopsy results
Abela C.B., et.al. Pyoderma gangrenosum. British Journal of Oral and Maxillofacial Surgery. SW17
0QT, UK. Department of Plastic and Reconstructive Surgery, St George’s Hospital, Blackshaw
Road, Tooting, London SW17 0QT, UK. 3 November 2005
Pyoderma
gangrenosum
• Inflammatory condition of skin
characterized histologically by
necrosis, ulceration and vasculitis
• 30-50 years old- most commonly
affected
• lesions most commonly found on
the lower extremities and trunk
• Its character is non infectious
• No identifiable infective pathogen,
unknown cause
Abela C.B., et.al. Pyoderma gangrenosum. British Journal of Oral and Maxillofacial Surgery. SW17 0QT, UK. Department of Plastic and
Reconstructive Surgery, St George’s Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK. 3 November 2005
Pyoderma gangrenosum: a review. A. Neil Crowson, Martin C. Mihm Jr., and Cynthia Magro, pp 98
*Mainly involves lower extremities
Pyoderma gangrenosum: Classification and management. Frank C. Powell, FRCPI, W. P. Daniel Su, MD,
Harold O. Perry, MD . Dublin, Ireland, and Rochester, Minnesota
Pathophysiology
• Involves dysregulation of immune system
• there may be a neutrophil dysfunction causing metabolic
oscillation and abnormal transit of neutrophils
• Altered eosinophil chemotaxis may be involved
Pyoderma gangrenosum: a challenge to the rheumatologist. Luciano Ferreira Coelho, Francine
Guilherme Correia, Fernanda Assis Ottoni, Flávia Patrícia Sena Teixeira Santos, Luciana Baptista
Pereira, Cristina Costa Duarte Lanna
http://emedicine.medscape.com/article/1123821-overview
Pathophysiology
• Direct immunofluorescence testing supports a
vasculopathy as playing a role in lesional propagation in
some patients by virtue of perivascular deposition of
immunoreactants, mainly IgM, C3 and fibrin
;
CrowsonAN,Magro
C, MihmMCJr.Py odermagangrenosum: a review.
;
JCutan Pathol 2003; 30: 97^107.#BlackwellMunksgaard 2003.
nodes or painful
sterile pustules
occur
central
ulceration
develops
Are deep and
reach dermis and
the
subcutaneous
tissue
classic ulcer is extensive, with infiltrated
borders, erythematous-violaceous,
undermined, with necrotic background and
granulation tissue
Picture taken from medscape.com
NB:
Ulcers may be single or multiple, are more frequent in
lower limbs and may be found in any other part of the
body.
Almost 30% of the patients present previous trauma
caused by a wound(pathergy).
Polypoid or bullous forms may rarely occur.
Pyoderma gangrenosum: a challenge to the rheumatologist. Luciano Ferreira Coelho, Francine
Guilherme Correia, Fernanda Assis Ottoni, Flávia Patrícia Sena Teixeira Santos, Luciana Baptista
Pereira, Cristina Costa Duarte Lanna
Histopathology
• Skin biopsies of all forms of PG show a central
zone of necrotizing suppurative inflammation.
;
Histopathology
• “Sweet-like” vascular reaction defined by
perivascular and intramural lymphocytic infiltrates
with a peripheral neutrophilic component, usually
without concomitant fibrinoid necrosis.
;
Diagnostic Approach
Diagnostic Approach
• Pyoderma gangrenosum is a diagnosis
of exclusion.
• Misdiagnosis of pyoderma
gangrenosum can result in substantial
complications in patients who have
other causes of severe cutaneous
ulceration.
• No laboratory finding is diagnostic of
paraderma gangrenosum.
Weenig R.H. et al. Skin ulcers misdiagnosed as pyoderma gangrenosum N Engl J
Med, Vol. 347, No. 18; 1412-7
Weenig R.H. et al. Skin ulcers misdiagnosed as pyoderma gangrenosum N Engl J
Med, Vol. 347, No. 18; 1412-7
Skin Biopsy
• Aim: to rule out diagnoses that mimic
pyoderma gangrenosum
• Protocol: Elliptical incisional biopsy preferable
to punch biopsy; include inflamed border and
ulcer edge at a depth that includes
subcutaneous fat
• Specimen from inflamed border — routine
histology (hematoxylin-and-eosin staining) and
special staining (Gram’s, methenamine silver,
and Fite) to detect microorganisms
• Specimen from edge of ulcer — culture in
appropriate culture media (to detect bacteria,
fungi, and atypical myobacteria)
Weenig R.H. et al. Skin ulcers misdiagnosed as pyoderma gangrenosum N Engl J
Med, Vol. 347, No. 18; 1412-7
Skin Biopsy
Early- stage lesions
Late-stage lesions
Advancing , inflamed
border lesions
dermal neutrophilic
abscess.
epidermal necrosis and
ulceration, superficial
dermal edema, and a
dense, mixed dermal
infiltrate that may
extend to the
panniculus.
dense perivascular
lymphocytic
inflammation,
which may at times be
associated with
vascular
destruction.
None of these histologic features is pathognomonic.
Weenig R.H. et al. Skin ulcers misdiagnosed as pyoderma gangrenosum N Engl J
Med, Vol. 347, No. 18; 1412-7
Abela C.B., et.al. Pyoderma gangrenosum. British Journal of Oral and Maxillofacial Surgery. SW17 0QT, UK. Department of
Plastic and Reconstructive Surgery, St George’s Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK. 3 November 2005
Direct Immunofluorescence
• may be the result of a hypersensitive
reaction of the immune system due to
an altered, exaggerated and
uncontrolled inflammatory response to
specific and non-specific stimuli,
leading to a neutrophilic vasculitis
• characterised by perivascular
deposition of immunoreactants, mainly
immunoglobulin M (IgM), C3 and fibrin
Carlesimo M et al, A case of pyoderma gangrenosum successfully treated with
intravenous immune globulin
Treatment
Tx: Pyoderma gangrenosum
• Medical
• Surgery
Surgical intervention in PG
• Ulcer excision, skin grafting
• Not supported by literatures because of
recurrence or even worsening of PG
Medical Intervention of PG
• Local therapy
– Topical treatment
Corticosteroid ointments
tacrolimus ointments
intralesional injections
• Systematic therapy
Systematic / Disseminated PG
• Corticosteroid / Cyclosporin
– First line of treatment
– Rapid response, stabilization of disease within
24hrs
Cyclosporin
• immunosuppressant drug
• Inhibits activation of transcription of
interleukin 2, lymphokine production
and interleukin release and, therefore,
leads to a reduced function of effector
T-cells
Corticosteroid
• Anti-inflammatory
• Immunosuppresant
• can be use in pulsed doses
Systematic / Disseminated PG
Medication
Recommended
dosage
Corticosteroids
0.5-1 mg methylprednisolone/kg/d
Corticosteroids (pulsed-dose)
1 g methylprednisolone/d for 1-5
days
Cyclosporine
5 mg cyclosporine/kg/d
Corticosteroids and cyclosporine
0.3-1 mg prednisolone/kg/d; 5 mg
cyclosporine/kg/d
Complication
• Corticosteroid
– Long term therapy may result to iatrogenic
Cushing’s syndrome
– Predispose patient to infection of wounds
• Cyclosporin
– Nephrotoxicity, hypertension, tremor,
increased risk of malignancy
Systematic / Disseminated PG
• mycophenolate mofetil; tacrolimus;
thalidomide; infliximab
– Alternative drugs
• Systemic antibiotics
– Inhibits secondary bacterial infections
Systematic / Disseminated PG
• Plasma Exchange
– consists of the removal of large volumes of
the patient' s plasma and replacing it with
exogenous plasma or plasma substitutes
• Action:
• removes from the circulation any
pathogenic material
• decrease T lymphocytes (indirect
action)
• normalize abnormal T4/T8 ratio
(indirect)
Potential complications include:
a.
b.
c.
d.
e.
f.
vasovagal reactions
hypovolemia or fluid
overload,
electrolyte abnormalities
infection of indwelling lines,
bleeding tendency caused by depletion of platelets or
clotting factors,
In Px given plasma as replacement fluid:
a.
b.
c.
d.
allergic reactions
transfusion-related infections (hepatitis, HIV)
difficulty in gaining vascular access,
lesions can develop at venipuncture sites.
Human intravenous immune globulin (IVIG)
Therapy
• human IVIG, 0.4 gm/kg per day, for 5 days
• effective in one patient with PGP after failure to respond to
prednisone, dapsone, cyclosporine,and pulse methylprednisolone
while therapy with cyclosporine and prednisone was continued.
* When used at the higher doses, IVIG possesses
immunosuppressive activity through poorly understood
mechanisms.
Systematic / Disseminated PG
• Human intravenous immune globulin
(IVIG) Therapy
– human IVIG, 0.4 gm/kg per day, for 5 days
– effective in one patient with PGP after failure
to respond to prednisone, dapsone,
cyclosporine,and pulse methylprednisolone
while therapy with cyclosporine and
prednisone was continued.
* When used at the higher doses, IVIG possesses
immunosuppressive
The principal disadvantages of this treatment
a. high cost
b. adverse effects (headache, chills, fever)
c. potential for transmission of diseases with
pooled sera.
Pseudomonas aeruginosa
These
bacteria show
resistance to
antibiotics
A combination of
two or more
antibiotics is
used to destroy
the bacteria
Antibiotic Selection takes into account local
patterns of antimicrobial susceptibility
Combination therapy
• in most severe infections due to P. Aeruginosa ,
two antipseudomonal antibiotics to which the
strain is sensitive should be administered
together
Benefits of this combined therapy:
1. Increased efficacy (more efficacious than
monotherapy)
2. Achievement of additive or synergistic killing
3. Prevention of antibiotic resistance
emergence
Fauci et al. Harrison’s Principles of Internal Medicine
Antimicrobial agents active against Pseudomonas
aeruginosa
1. aminoglycosides (gentamicin, amikacin, tobramycin)
2. quinolones (ciprofloxacin, levofloxacin, and moxifloxacin)
3. cephalosporins (ceftazidime, cefepime, cefoperazone, cefpirome, but not
cefuroxime, ceftriaxone, cefotaxime)
4. ureidopenicillins and carboxypenicillins (piperacillin, ticarcillin: P.
aeruginosa is intrinsically resistant to all other penicillins)
5. carbapenems (meropenem, imipenem, doripenem, but not ertapenem)
6. polymyxins (polymyxin B and colistin)
7. monobactams (aztreonam)
Fauci et al. Harrison’s Principles of Internal Medicine
Duration of Antibiotic therapy
depends on:
1.Type
2.Location
3.Severity of infection
* In general: therapy lasts for weeks or
even months rather than days
Fauci et al. Harrison’s Principles of Internal Medicine
Antibiotic Resistance in P. aeruginosa is
both:
Intrinsic
- as reflected by the relative paucity of
antibiotics with inherent activity against wild
type strains
Acquired
- as defined by high level resistance to
agents that normally would be expected to
exhibit antimicrobial activity
Fauci et al. Harrison’s Principles of Internal Medicine
Increased severity
of illness in
hospitalized
patients
Inadequate infection
control procedures
Expanding use of
immunosuppressive
therapies
Increase
in
Antibiotic
resistance
Growing antibiotic
use
Fauci et al. Harrison’s Principles of Internal Medicine
Antimicrobial agents
selected on basis of
extended susceptibility
testing
Surgical drainage
and removal of
infected tissues
Therapy for
RESISTANT
P. aeruginosa
infections
Increased
treatment
duration
Fauci et al. Harrison’s Principles of Internal Medicine
Follow-up and Monitoring
• Close, continuous follow-up.
• Monitor response to side effects of
therapy.
Effect of long term steroid therapy
•
Glaucoma and cataracts
•
Fluid retention, edema in lower legs
•
Increased blood pressure
•
Weight gain, redistribution of body fat
•
High blood sugar and worsening of diabetes
Prednisone and other corticosteroids:
Balance the risks and benefits
www.mayoclinic.com/health/steroids/HQ01431
Effect of long term steroid therapy
•
•
•
•
•
Increased risk of infections
Osteoporosis and fractures
Menstrual irregularities
Suppressed adrenal gland hormone production
Thin skin, easy bruisability
Prednisone and other corticosteroids: Balance the risks
and benefits www.mayoclinic.com/health/steroids/HQ01431
Follow up of patients on long term
steroid therapy
• Vitamin D and calcium supplementation, and a
baseline bone densitometry
• Antiresorptive therapy to prevent osteoporosis
• Fasting Blood Sugar
• Ophthalmologic exam
• If no response to treatment,
reconsider diagnosis.
109
THANK YOU FOR
LISTENING!!!
110