Medicine II Infectious Diseases BGD 1 Subsection B1 1.

Medicine IIMedicine IIInfectious DiseasesInfectious DiseasesBGD 1BGD 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%

• 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:Chief Complaint:

non-healing ulcer on the left legnon-healing ulcer on the left leg

3

4

History of Present IllnessHistory 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

5


•persistence of the swelling

•Consult to a “manghihilot”

•Massage therapy was done

•undocumented fever temporarily relieved by intake of Paracetamol 500mg tab


• 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


•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


•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


•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


10


•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.


11


•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.


12


•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


13


•rapid increase in size of the wound

•increase in the severity of the pain now grade 10/10

ADMISSIONADMISSION


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Review of SystemsReview 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

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• 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 relationship difficulties

Review of SystemsReview of Systems

16

• (+) Blood transfusion, number of units unrecalled when the patient underwent above the knee amputation (2007)

• (-) Hypertension • (-) allergies • (-) asthma• (-) thyroid diseases• (-) DM• (-) skin disease

Past Medical HistoryPast Medical History

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• nulligravid

OB HistoryOB History

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• M- 13 years old

• I-28- 30 days

• D- 3 days

• A-2 ppd moderately soaked

• S- dysmenorrhea Day 1

Menstrual HistoryMenstrual History

19

• the patient denies any sexual contact

Sexual HistorySexual History

20

• Non-smoker• Non-alcoholic beverage drinker• No diet preferences

Personal & Social HistoryPersonal & Social History

21

• (+) CVD mother, died at 76 years old • (+) sibling MI• (-) skin disease• (-) DM• (-) asthma• (-) allergies• (-) thyroid diseases• (-) autoimmune disorders

Family HistoryFamily History

22

Physical ExaminationPhysical 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) BMI 22

23

• (+) 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.

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• 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


25

• 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


Neurologic ExaminationNeurologic Examination

• Conscious, coherent, oriented to three spheres, GCS 15

• Cranial Nerves:– 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

– (+) gag reflex– can shrug shoulders– turns head side to side against

resistance• tongue midline on protrusion

• 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 FEATURESSALIENT 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

• 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

• 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

28

AssessmentAssessment

Differential Diagnosis

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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): 319-3281175-0561/02/0005-0319/$25.00/0


Morphological Manifestations

• Granulomatous inflammation

• Variable necrosis

• Variable vasculitis

Demonstration of M. tuberculosis via:1. Culture

2. Staining

3. PCRCutaneous Tuberculosis: Diagnosis and TreatmentAm J Clin Dermatol 2002; 3 (5): 319-328

1175-0561/02/0005-0319/$25.00/0


Classification Tuberculous ChancreTuberculosis Verrucosa CutisLupus VulgarisScrofulodermaOrificial TuberculosisMiliary TuberculosisMetastatic Tuberculosis Abscess



Most plausible type for differential diagnosis based on course and features of the lesion:

Tuberculous Chancre Lupus Vulgaris, ulcerative typeScrofuloderma



Tuberculous Chancre



Lupus Vulgaris



Scrofuloderma



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.


• 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


• 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


(Group A Streptococci)A. Definite case1. Necrosis of soft tissues with involvement of the

fasciaPLUS2. Serious systemic disease, including one or

more of the following:a) Deathb) Shock (systolic blood pressure <90 mm of

Hg).c) Disseminated intravascular coagulopathy


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


B. Suspected case1 . 1 + 2 and serologic confirmation of

group A streptococcal infection by a 4-fold rise against:

a) streptolysin Ob) DNase B2. 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.


• 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

• 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).


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.


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.


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.


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/antiphospholipid-

syndrome/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

http://www.mayoclinic.com/health/antiphospholipid-syndrome/DS00921/DSECTION=causes

• 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, small-intestine 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

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

??

? 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 2005Pyoderma gangrenosum: a review. A. Neil Crowson, Martin C. Mihm Jr., and Cynthia Magro, pp 98

Pyoderma gangrenosum: Classification and management. Frank C. Powell, FRCPI, W. P. Daniel Su, MD, Harold O. Perry, MD . Dublin, Ireland, and Rochester, Minnesota

*Mainly involves lower extremities

http://emedicine.medscape.com/article/1123821-overview

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

CrowsonAN,Magro C, MihmMCJr.Py odermagangrenosum: a review.JCutan Pathol 2003; 30: 97^107.#BlackwellMunksgaard 2003.

;

;

classic ulcer is extensive, with infiltrated borders, erythematous-violaceous, undermined, with necrotic background and granulation tissue

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

Picture taken from medscape.com

• Skin biopsies of all forms of PG show a central zone of necrotizing suppurative inflammation.

;

• “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


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)


Skin Biopsy

Early- stage lesions Late-stage lesions Advancing , inflamedborder 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 vasculardestruction.


None of these histologic features is pathognomonic.

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


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


• mycophenolate mofetil; tacrolimus; thalidomide; infliximab– Alternative drugs

• Systemic antibiotics– Inhibits secondary bacterial infections


• 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.vasovagal reactionsb.hypovolemia or fluidc.overload, d.electrolyte abnormalitiese.infection of indwelling lines, f.bleeding tendency caused by depletion of platelets or clotting factors,

In Px given plasma as replacement fluid:•allergic reactionsa.transfusion-related infections (hepatitis, HIV)b.difficulty in gaining vascular access,c.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.


• 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 costb.adverse effects (headache, chills, fever)c.potential for transmission of diseases with pooled sera.

Pseudomonas aeruginosa

Antibiotic Selection takes into account local patterns of antimicrobial susceptibilityAntibiotic 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

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)


Duration of Antibiotic therapy depends on:

1.Type2.Location3.Severity of infection

* In general: therapy lasts for weeks or even months rather than days


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 activityFauci 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.

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Medicine II Infectious Diseases BGD 1 Subsection B1 1.

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