Infectious Diseases 1: Bacterial Infections II (V1) PDF

PATHOLOGY | TRANS 4C LE Infectious Diseases 1: Bacterial Infections II DR. ARLENE SANTOS, MD, FPSP | (09/...

PATHOLOGY | TRANS 4C LE Infectious Diseases 1: Bacterial Infections II DR. ARLENE SANTOS, MD, FPSP | (09/27/2024) | Version 1 02 OUTLINE Characteristic histologic finding in syphilis: Proliferative I. Spirochetes A. Chlamydial Infections end-arteritis surrounding small vessels A. Syphilis B. Rickettsial Infections → Microscopic findings from a lesion on the skin from a B. Lyme Disease IV. Review Questions patient with secondary syphilis II. Anaerobic Bacteria V. References → Note the following: A. Clostridial Infections VI. Formative quiz 1. Blood vessel w/ endothelial swelling III.Obligate Intracellular 2. Presence of numerous plasma cells Bacteria 3. Presence of many lymphocytes Must Lecturer Book Previous Youtube Inset: Immunohistochemistry directed against ❗️ Know 💬 📖 📋 Trans 🔺 Video Treponema pallidum ANCILLARY TESTS SUMMARY OF ABBREVIATIONS Histochemistry 📋 PCR Polymerase Chain Reaction → Warthin Starry stain (and Steiner Silver stain) LEARNING OBJECTIVES Silver nitrate based staining method ✔ Identify and enumerate different diseases caused by Spirochetes ✔ Identify and differentiate the stages of Syphilis ✔ Identify and differentiate the stages of Lyme disease ✔ Identify and discuss the type of Clostridial infections ✔ Discuss the mechanisms involved in infections regarding obligate intracellular bacteria 📖 Spirochetes I. SPIROCHETES are gram-negative, slender corkscrew-shaped bacteria with axial periplasmic flagella wound around a helical protoplasm A. SYPHILIS Caused by Treponema pallidum Usual mode of transmission: Sexual Intercourse Figure 2. Spirochetes on a Silver stain[Lecturer’s PPT] → Any sexually active person can get syphilis through ▪ Spirochetes are spiral or cork-screw shaped unprotected anal, vaginal, or oral sex bacteria which appear like a helical coil Can be transmitted to the fetus during pregnancy → Dark field microscopy → Active disease during pregnancy results in congenital syphilis Gross: Painless, shallow ulcer Divided into three stages: Primary, Secondary, and Tertiary → Many spirochetes are seen within the chancre (primary syphilis) and condyloma lata (secondary syphilis) → Spirochetes are scant in gummas (tertiary syphilis) MICROSCOPIC FINDINGS Figure 3. Dark field microscopy of T. pallidum[Lecturer’s PPT] ▪ Taken from scrapings from base of the chancre Immunohistochemistry → Detects spirochete antibodies PCR → Amplification of bacterial DNA from infected tissue Serologic Testing → Screening (Non-treponemal antibody test) ▪ Venereal Disease Research Laboratory (VDRL) test Figure 1. Histologic findings: Lesion on the skin from a ▪ Rapid plasma reagin (RPR) test patient with secondary syphilis. Inset: Immunohistochemistry ▪ Enzyme immunoassay (EIA) test directed against Treponema pallidum[Lecturer’s PPT] → Diagnosis (Treponemal antibody test) ▪ Fluorescent treponemal antibody absorption test ▪ T. pallidum particle agglutination assay LE 2 TG 8 | Genoveza, *Gonzales, J., Gonzales, M. TE | *Gonzales, J. AVPAA | R. Laulita PAGE 1 of 13 TRANS 4C T., Go, M. A., Go, S VPAA | J. Magtibay PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS 📋▪Non-treponemal Microhemagglutination assay antibody test: measure antibody to cardiolipin, a phospholipid present in both host tissues PRIMARY SYPHILIS Chancre at the site of treponemal invasion Appears 3 weeks after contact with an infected individual; and T. pallidum heals with or without therapy ▪ Very sensitive for secondary syphilis Treponemes spread by hematologic & lymphatic ▪ Moderately sensitive for primary syphilis dissemination throughout the body even before the ▪ Less sensitive for tertiary or latent syphilis appearance of the chancre ▪ Can be used to monitor therapy as levels of non-treponemal antibody levels fall with successful 📋 treatment Treponemal antibody test: measure antibodies that specifically react with T. pallidum ▪ Very sensitive for secondary, tertiary, and latent syphilis (non-primary syphilis) ▪ Moderately sensitive for primary syphilis ▪ Can be used to determine positivity from a non-treponemal test that is positive PATHOGENESIS[Robbins & Cotran, Chapter 8] Proliferative endarteritis affecting small vessels with a surrounding plasma cell-rich infiltrate is characteristic of all stages of syphilis Figure 5. Chancre in the Scrotum and Penis[Lecture PPT] Immune response to T. pallidum reduces the burden of Begins as a red, firm, nontender, papule which erodes bacteria and can lead to resolution of local lesions but to form a shallow, clean-based ulcer with indurated does not reliably eliminate the systemic infection borders (button-like mass) Superficial sites of infection (chancres and rashes) have → Syphilitic chancre is also called a “hard chancre” intense inflammatory infiltrate that includes T cells, because of the indurated or “hard” border plasma cells and macrophages that surround the bacteria Common sites in men → The infiltrating CD4+ T cells are TH1 cells that may → Penis activate macrophages to kill the bacteria → Scrotum Treponemal-specific antibodies are detectable → Anus → Can activate complement in the lesion → Rectum → Can opsonize bacteria for phagocytosis by Microscopic finding: proliferative or obliterative macrophages endarteritis; many treponemes In most patients, the organism persists despite these host responses TprK, an outer membrane protein of T. pallidum → accumulates structural diversity during the course of infection through gene conversion between silent donor sites and the tprK gene → Contributes to antigenic diversity that allows the organism to persist STAGES OF SYPHILIS Figure 6. Hard chancre in Women[Lecture PPT] Common sites in women → Cervix → Vulva → Perineum Figure 7. Hard chancre (R) on the surface of lower lip[Lecture PPT] Chancre acquired through oral sex; occurs at site of treponemal invasion Figure 4. Protean Manifestations of Syphilis[Lecture PPT] PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 2 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS SECONDARY SYPHILIS Occurs 2-10 weeks after the primary chancre in 75% of untreated people Lasts several weeks then the person enters the latent state of the disease Manifestations of secondary syphilis are found on the skin and mucous membranes → Rash on the palms and soles Figure 8. L: Hard chancre on the surface of the tongue, an ▪ may appear as red, brown macules ulcer w/ indurated borders on the dorsum of the tongue; R: ▪ maybe papular, pustular, follicular. annular or scaling Immunohistochemical staining, revealing Treponema → Condyloma latum (Plural form: condylomata lata) pallidum antibodies on the granulation tissue overlying the - broad-based elevated plaques on moist areas of ulcer & on the walls of lumen of capillaries at its margin skin [Lecturer’s PPT] → Silvery-gray, superficial erosions on the oral, pharyngeal & anogenital membranes Figure 9. Hard chancre on the surface of the tongue [Lecturer’s PPT] Figure 12. Rash on the sole of the foot [Lecturer’s PPT] Figure 10. Microscopic Findings: Syphilitic chancre - Vulva [Lecturer’s PPT] \ HISTOPATHOLOGY OF PRIMARY SYPHILIS Obliterative end-arteritis consists of concentric endothelial and fibroblastic proliferative thickening. The blood vessel is surrounded by many mononuclear leukocytes Figure 13. Manifestations of secondary syphilis: A) Rashes on palms; B) Condyloma lata on the anogenital region; C) SIlvery-gray, superficial erosion [Lecturer’s PPT] Other clinical findings: lymphadenopathy, mild fever, malaise & weight loss Figure 11. Obliterative end-arteritis: blood vessel with a Microscopic finding in secondary syphilis: proliferative thickened wall (blue dash line); mononuclear leukocytes or obliterative endarteritis; many treponemes surrounding the blood vessel (magenta dash lines)[Lecturer’s Mucocutaneous changes - maybe macular, popular, PPT] pustular, follicular, annular & scaling PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 3 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS 📋 TERTIARY SYPHILIS 2. Benign Tertiary Syphilis Three main manifestations Characterized by the formation of gummas → Cardiovascular Syphilis Gummas → Neurosyphilis → Appear as nodular lesions or destructive, ulcerative → Benign Tertiary Syphilis lesions in many organs but most commonly in bone, ▪ Benign tertiary syphilis is characterized by formation skin, mucous membranes of the upper airway & of gummas mouth Occurs in 1/3 of untreated patients after a latent period of → Probably related to delayed hypersensitivity to 5 years or more Treponema pallidum Common sites involved in tertiary syphilis: → Macroscopic finding: white-gray to rubbery, singly → Aorta or multiple; microscopic to large masses like TB → CNS granulomas → Liver → Bone → Testes CLINICAL MANIFESTATIONS 1. Cardiovascular Syphilis Aortitis - Most common form of CVS syphilis → progressive dilatation of aortic root & arch → aortic valve insufficiency & aneurysm of proximal aorta ▪ Aneurysm - localized abnormal dilatation of a blood vessel or the heart In syphilitic aortitis → obliterative endarteritis→endothelial proliferation & Figure 16. Gummas [Lecturer’s PPT] intimal fibrosis→concentric endothelial & fibroblastic → Microscopic finding: Central area of necrosis thickening of the vasa vasorum of the proximal surrounded by palisading plump macrophages & aorta→scarring of tunica media of the proximal fibroblasts surrounded by plasma cells & aortic wall→loss of elasticity lymphocytes; scanty to absent treponemes ▪ Vasa vasorum - blood vessels supplying the walls of arteries & veins → obliterative endarteritis → subintimal scarring→myocardial ischemia → obliterative endarteritis→weakened vascular wall→abnormal dilatation Figure 17. Liver (Trichrome stain) - Gummas→ Scarring (Fibrosis - Yellow arrow) → Hepar lobatum Hepatocytes (Green arrow) Figure 14. Ruptured syphilitic aneurysm (aortic arch)[Lecturer’s 📋 3. Neurosyphilis PPT] Takes one of several form: designated meningovascular syphilis, tabes dorsalis, and genital Much of the pathology of syphilis can be ascribed to paresis the ischemia produced by the vascular lesions Individuals affected by HIV are at increased risk because of impaired cell-mediated immunity CONGENITAL SYPHILIS Occurs most frequently during maternal primary and secondary syphilis Causes intrauterine death & perinatal death in 25% of cases Infantile Syphilis → Before two years of life → Pathologic findings: ▪ Nasal discharge & congestion (snuffles) Figure 15. Obliterative endarteritis from a case of syphilitic ▪ Desquamating bullous rash around mouth & anus & aortitis, affecting vasa vasorum in the adventitia of the aorta; of hands & feet Concentric endothelial & fibroblastic thickening (blue dash ▪ Osteochondritis line) → lead to obstruction of the small blood vessels ▪ Periostitis of tibia giving rise to anterior bowing or [Lecturer’s PPT] saber shin deformity PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 4 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS ▪ Diffuse fibrosis of liver & interstitial fibrosis of the Major arthropod borne disease in the USA, europe, and lungs Japan Childhood Syphilis (Tardive Syphilis) → Involves multiple organs → After two years of Life Distinctive feature of Lyme arthritis → Pathologic Findings: → Arteritis with onion skin-like lesions ▪ Hutchinson’s triad Late stage: Extensive erosion of cartilage 1. Interstitial keratitis Mainstay of diagnosis: Serology 2. Eight nerve deafness CLINICAL STAGES OF LYME DISEASE 3. Hutchinson teeth - Refers to small incisors w/ notches in the enamel resembling peg cells or screwdriver Figure 18. Destruction of vomer→collapse of the bridge of the nose giving rise to the saddle-nose deformity [Lecturer’s PPT] Figure 22. Clinical Stages of Lyme Disease[Lecture PPT] Lyme disease is divided in 3 stages: → Stage 1 - Early localized disease - erythema migrans at site of the tick bite Figure 19. Hutchinson teeth; see notches (Blue arrow) → Stage 2 - early disseminated stage - hematogenous [Lecturer’s PPT] dissemination of spirochetes throughout the body → Stage 3 - late disseminated stage - manifests many months after the tick bite STAGE 1: EARLY LOCALIZED DISEASE Erythema migrans (aka Erythema chronicum migrans) at the site of tick bite → Causes an expanding area of redness with pale center Proliferation of spirochetes in the demis at the site of the tick bite → Elicits a host dermal inflammatory response → erythema migrans Figure 20. Pancreas - Obliterative endarteritis (Yellow arrow); Fibrosis (Blue arrow); Pancreatic acinus (Green arrow) II. LYME DISEASE Causative agent: Borrelia burgdorferi Transmitted from rodents to humans by deer ticks; Ixodes scapularis Figure 23. Erythema migrans[Lecture PPT] “Target” Appearance → Pale center and an expanding area of redness Maybe accompanied by fever and lymphadenopathy Figure 21. (L) Ixodes scapularis. (R) Dark field microscopy Erythema migrans occurs at the site of the tick bite. showing helical shape of B. burgdorferi[Lecture PPT] The bite of the tick causes an expanding area of redness with a pale center. PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 5 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS ▪ Arteritis producing onion skin-like lesions resembling those seen in lupus ▪ Extensive erosion of cartilage → CSF ▪ Hypercellular due to increased lymphoplasmacytic infiltrates and antispirochetes IgGs in lyme meningitis Figure 24. Target appearance of erythema migrans[Lecture PPT] STAGE 2: EARLY DISSEMINATED STAGE 📋 Hematogenous dissemination of spirochetes throughout the body Clinical findings: Figure 26. Abundant lymphocytes, few histiocytes, and neutrophils in stroma of the synovium[Lecture PPT] → Secondary skin lesions → Lymphadenopathy ❗️ MUST KNOW → Migratory joint and muscle pain Lyme disease is caused by Borrelia burgdorferi → Cardiac arrhythmias → Transmission: rodent to humans by deer ticks → Meningitis (often associated with cranial nerve (Ixodes scapularis) involvement) → Distinctive feature: Arteritis with onion skin-like lesions STAGE 3: LATE DISSEMINATED STAGE → Mainstay method of dx: Serology Manifests after many months after tick bite Clinical Stages Lyme arthritis → Stage 1 (Early Localized Disease) → Chronic arthritis with severe damage to large joints ▪ Spirochetes multiply and spread in the dermis at → Swollen knees due to lyme arthritis the site of tick bite causing erythema migrans → Large joints are affected ▪ “Target” appearance of lesions ▪ Most common: knees → Stage 2 (Early Disseminated Infection) → Painful and swollen joints last for a few days to a few ▪ Hematogenous spirochetes spread throughout the months body ▪ Clinical findings: − Secondary skin lesions − Lymphadenopathy − Migratory joint and muscle pain − Cardiac arrhythmias − Meningitis o Often associated with cranial nerve involvement → Stage 3 (Late Disseminated Infection) ▪ Lyme arthritis Figure 25. Lyme arthritis[Lecture PPT] − Chronic arthritis with severe damage to large joints Other chronic complications ▪ Acrodermatitis chronica atrophicans → Acrodermatitis chronica atrophicans − red/bluish lesions on extensor surfaces of ▪ red/bluish lesions on extensor surfaces of extremities extremities ▪ Polyneuropathy and encephalitis → Polyneuropathy and encephalitis Inflammatory lesions in Lyme disease likely triggered by II. ANAEROBIC BACTERIA T cells and cytokines Abcesses and Peritonitis caused by anaerobes Chronic manifestations of Lyme disease → Maybe caused by the immune response against 📋 → When introduced into normally sterile sites Balance of organisms is upset and pathogenic some, as yet, unknown bacterial antigen that cross reacts with a self-antigen 📋 anaerobes overgrow Many are normal microbiota in body sites with low CHRONIC SYNOVITIS Microscopic Findings: 📋 oxygen levels Clostridial Infections: Diseases are caused by environmental anaerobes → Skin ▪ Edema, lymphocytic and plasma cell infiltrates → Clostridium tetani → Synovium (early Lyme arthritis) → Clostridium botulinum ▪ Villous hypertrophy, lining cell hyperplasia, and → Clostridium perfringens abundant lymphocytes → Late lyme arthritis PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 6 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS CLOSTRIDIAL INFECTIONS PATHOLOGIC FINDINGS IN CLOSTRIDIAL CELLULITIS 📋 A. DISEASES CAUSED BY CLOSTRIDIUM Clostridium spp. are anaerobic, spore-forming, gram-positive bacilli C. perfringens causes extremely painful & progressive soft tissue infections(cellulitis;myositis; gas gangrene) Clostridial cellulitis Table 1. Diseases caused by Clostridium spp. → Localized infection in a superficial wound occuring 2-3 Infectious Agent Disease days after injury C. perfringens Cellulitis → Infection may spread extensively along fascial planes, C. septicum Gas gangrene often w./ evident crepitation & gas bubbling C. tetani Tetanus → Toxicity is less severe than myonecrosis (clostridial C. botulinum Botulism gas gangrene); Minimal pain; Bullae (Yellow arrow) C. difficile Pseudomembranous colitis evident Characteristics of Clostridial cellulitis: B. ANCILLARY TESTS → Foul smelling Direct Examination (Smear & Gram Stain) → Thin, discolored exudate (Brown, serous exudate) → Gram stain of wound smear: show gram-positive bacilli → Quick and Wide tissue destruction with or without spores Histologic findings: ▪ Critical for diagnosis of gas gangrene → Extensive areas of tissue necrosis but few Immunoassays neutrophils and gram-positive bacilli → A variety of assays available to diagnose C. difficile by enzyme immunoassay Cell Culture / Animal Cytotoxicity Assay → Traditional gold standard for detection of toxigenic C. difficile CLOSTRIDIUM PERFRINGENS Gram stain: → Box-shaped, gram-positive, purple bacilli Pathogenesis: → Obligate anaerobe → Tissue death is essential for growth in host → Releases collagenase and hyaluronidase ▪ Degrades extracellular matrix proteins which contributes to bacterial invasiveness → Secretes 14 toxins Figure 28. Cellulitis, Bullae (Yellow arrow)[Lecturer’s PPT] ▪ Most important toxin: α-toxin PATHOLOGIC FINDINGS IN GAS GANGRENE − Degrades lecithin (major component of Clostridial gas gangrene membranes) → destroys RBCs, platelets, and → a necrotizing soft tissue infection of skeletal muscle muscle cells caused by toxin & gas-producing Clostridial species − Has sphingomyelinase activity → contributes → Wound site initially pale → becomes red or bronze 📋 to nerve sheath damage Ingestion of contaminated food causes brief diarrhea often w/ blebs or bullae→ finally turns blackish-green or bluish-black → Affected area is edematous & tender to palpation; w/ ▪ Spores in contaminated meat usually survives crepitation; foul-smelling 📋 cooking and proliferates in cooling food C. perfringens enterotoxin ▪ Forms pores in the epithelial cell membranes → Also known a clostridial myonecrosis − Cause cell lysis and disruption of tight junctions between epithelial cells HISTOPATHOLOGY OF CLOSTRIDIUM PERFINGENS Figure 29. Gas Gangrene [Lecturer’s PPT] → In Figure 30, formation of bullous vesicles that rupture → Bullae are secondary to an extensive fluid exudate lacking in inflammatory cells → Formation of gas bubbles secondary to bacterial fermentation → Affected muscles become bluish-black, friable to Figure 27. Gangrenous tissue with C. perfringens; Gram semifluid as a result of proteolytic action of bacterial positive (purple) boxcar shaped bacilli [Lecturer’s PPT] enzymes PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 7 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS Figure 30. Initially-marked edema & enzymatic necrosis of Figure 34. HPO of the skeletal muscle: Necrotic muscle cell muscle cells 1-3 days after injury [Lecturer’s PPT] - Hypereosinophilic & w/out a nucleus (Arrow 1); Some A case of a elderly diabetic, male who was admitted inflammatory infiltrates (Arrow 2); A blood vessel w/ because of fever & chills; had a swollen lower extremity thrombosis (Arrow 3) [Lecturer’s PPT] on the 2nd hospital day w/c became red & crepitant GRAM STAIN OF A TISSUE (BROWN AND BREN) Figure 31. Image on the left, affected area (white arrow); image on the right, blebs (black arrow) due to gas formation by Clostridium perfringens [Lecturer’s PPT] Figure 35. Gram positive bacilli [Lecturer’s PPT] III. OBLIGATE INTRACELLULAR BACTERIA A. CHLAMYDIAL INFECTIONS Most common bacterial STI in US Leading cause of infertility Often asymptomatic Diagnosis: Amplified DNA; fluorescent monoclonal AB screening PATHOLOGIC FINDINGS IN CHLAMYDIAL INFECTIONS Genital infection in women: → Often asymptomatic, sometimes mucopurulent cervicitis/urethritis → Endometritis / salpingitis / peritonitis (Pelvic Figure 32. LPO of the muscle fascicles: Gas formation Inflammatory Disease) (clear areas indicated by the black arrow)[Lecturer’s PPT] → Sequelae can include sterility & ectopic pregnancy Figure 33. HPO of the skeletal muscle: Gas (Arrow 1); Dark blue staining bacterial organisms (Arrow 2); No inflammatory infiltrate seen [Lecturer’s PPT] Figure 36. Beefy red mucosa in chlamydial infection [Lecturer’s PPT] PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 8 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS PATHOLOGIC FINDINGS IN CHLAMYDIA URETHRITIS Genital infection in males: → Major cause of nongonococcal urethritis: Whitish/clear discharge, maybe scant; 1% develop reactive arthritis → Epididymitis, prostatitis, and proctitis Figure 39. [L] Male with enlarged lymph nodes in both groins. Lymphadenitis manifests as enlarged and inflamed lymph nodes also known as buboes. [R] Female with an enlarged inguinal lymph node.[Lecturer’s PPT] Figure 37. Non-gonococcal urethritis: Mucoid discharge [Lecturer’s PPT] LYMPHOGRANULOMA VENEREUM Caused by Chlamydia serotypes L1, L2, and L3 Often confused with syphilis, herpes, or chancroid Figure 40. 60 year old male with an ulcer on the penis and Mainly affects lymphoid tissue inguinal lymphadenopathy.[Lecturer’s PPT] ❗ Initial ulcer ordinarily pass away unnoticed Histologic hallmark: Initial clinical manifestation: Stellate abscesses → Swelling of the inguinal lymph node due to stellate ▪ Neutrophils in the area of necrosis abscesses surrounded by epithelioid cells Extensive scarring → Fistulas and strictures 3 stages: → Formation of a small genital papule → Adenitis (buboes) and development of Systemic Symptoms ▪ Fever ▪ Headache ▪ Myalgia → Chronic disease that includes fistulas, fibrosis, scarring and elephantiasis of genitalia due to lymphatic obstruction Alternatively, may present as severe proctitis in men who have sex with other men (MSM) Diagnostic tests: → Frei test → Tissue culture Figure 41. Lymph node in LPO. Histological hallmark: → Monoclonal antibody test stellate abscesses (neutrophils in the area of necrosis Rayney: 11 case of SCCA on lymphogranulomatous encircled with apple green dashed lines). Microscopic strictures findings: Granulomatous inflammatory reactions associated with stellate abscess. [Lecturer’s PPT] Figure 42. Lymph node in HPO. Shows a multinucleated cell (yellow arrow) which is a part of the granulomatous reaction and neutrophils admixed with necrotic debris. [Lecturer’s PPT] Figure 38. Groove sign in a man with LV [Lecturer’s PPT] PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 9 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS 📋 MUST KNOW Obligate intracellular bacteria: Proliferate within host Characterized initially by rashes on the wrist and ankles then will become generalized cell only → Maculopapular rash Chlamydial Infections ▪ Petechial or Hemorrhagic → Most common bacterial STI in US → Thrombosed vessel → Leading cause of infertility and blindness → Often asymptomatic → Has two forms: ▪ Elementary for “Enfectious form” ▪ Reticulate for “Replicative form” → Elementary body ▪ Infectious form ▪ Metabolically inactive, spore-like structure Figure 43. (L) Initial rash on patients with RMSF. (R) Eschar → Reticulate body found on the trunk and leg with the characteristic ulceration ▪ Replicative form and black scab [Lecturer’s PPT] ▪ Metabolically active form Microscopy → Chlamydia trachomatis serotypes → Blood vessel surrounded by mononuclear ▪ A,B,C - cause trachoma (an ocular infection of inflammatory cells children) → Vascular thrombosis may lead to micro infarcts in ▪ D-K - cause urogenital infections & inclusion the brain conjunctivitis ▪ L1, L2, L3 - cause lymphogranuloma venereum Chlamydia Urethritis → Characterized by mucopurulent discharge containing a predominance of neutrophils → Major cause of nongonococcal urethritis in males Lymphogranuloma Venereum → Caused by Chlamydia serotypes L1, L2, L3 → Mainly affects lymphoid tissue → 3 Stages: 1. Formation of a small genital papule 2. Adenitis (buboes) and development of systemic symptoms Figure 44. RMSF with Thrombosed vessel & Vasculitis [Lecturer’s PPT] 3. Chronic diseases include fistulas, fibrosis, scarring, and elephantiasis of genitalia due to lymphatic obstruction − Present as severe proctitis in men who have 📖 SCRUB TYPHUS Caused by Orientia tsutsugamushi Characterized by an Eschar [Robbins] sex with other men → Punched out ulcer with a black scab B. RICKETTSIAL INFECTIONS → Seen at the site of the chigger (mite/tick) bite Most Rickettsial infections are transmitted by insect Typhus group - rash begins on the trunk then vectors progresses to the extremities → Q fever - aerosols Severe manifestations of rickettsial infections are due to → Epidemic typhus - lice infection of endothelial cells and consequent → RMSF - ticks endothelial dysfunction & injury → Scrub typhus - mites Widespread endothelial dysfunction can cause: Predominantly infect endothelial cells and vascular → Shock smooth muscle cells- vasculitis → Peripheral & pulmonary edema Mode of transmission: → Disseminated intravascular coagulation → Tick or mite bite → Renal failure → Entry through excoriations on the skin by the → Various CNS manifestations rickettsia found in louse’s feces → Contamination of fingers while removing ticks → Inhalation Microscopy: → Thrombosed vessels → Vasculitis Diagnostic tests: → Immunostaining and antibody detection 📖 📖 ROCKY MOUNTAIN SPOTTED FEVER Caused by Rickettsia rickettsii [Robbins] It begins as a nonspecific severe illness with fever, myalgias, and gastrointestinal distress, and progresses to a Figure 45. Scrub typhus- Eschar (punched out ulcer with a widespread macular then petechial rash that can involve black scab) seen at the site of the chigger (mite) bite [Lecturer’s the palms and soles [Robbins] PPT] PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 10 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS 📖 TYPHUS FEVER[Robbins] 1. C. Rickettsial infections predominantly infect endothelial cells and Mild cases: Gross changes limited to a rash and small vascular smooth muscle cells (vasculitis). Thrombosed vessels and vasculitis (presence of vasculitis is the most important 📖 hemorrhages due to the vascular lesions Severe cases: Areas of necrosis of the skin and gangrene of the tips of the fingers, nose, earlobes, scrotum, histologic feature) 2. B. Choice A is not the answer because spirochetes are scanty in lesions of tertiary syphilis. Choice C can only be seen in tertiary penis, and vulva syphilis Typhus nodule (Microscopy) 3. A. Localized infection. Spirochetes multiply and spread in the → Characteristic finding in the brain dermis at the site of a tick bite, causing an expanding area of → Focal microglial proliferation with T lymphocytes redness, often with pale center - this lesion is called erythema and macrophages chronicum migrans 4. B. Spirochetes are gram-negative, slender, and corkscrew-shaped which may cause syphilis, relapsing fever and lyme disease. Soft chancre or chancroid is associated with Chlamydial infection 5. C. Lymphogranuloma venereum is caused by Chlamydia trachomatis serotypes L1, L2 and L3. The infection initially manifests as a small papule on the genital mucosa or the nearby skin. The growth of the organism and the host response in the draining lymph nodes produce swollen and tender lymph nodes. The characteristic finding in the affected lymph node is a granulomatous inflammation associated with stellate abscess V. REFERENCES 2026 Transcription Robbins & Cotran Pathologic Basis of Disease by Kumar, Abas & Aster Pathology of Infectious Diseases, Part 4 - Dr. A Santos (Asynch) Figure 46. Typhus nodule [Lecturer’s PPT] III. REVIEW QUESTIONS 1. The vasculitis seen in Rickettsial infections is due to the multiplication of the infectious agent in the: a. Tunica media of the veins b. Endothelial cells lining the lymphatics c. Endothelial cells lining the blood vessels 2. Which of the following histologic findings is seen in all stages of syphilis? a. Abundant spirochetes b. Proliferative and end-arteritis c. Gumma formation 3. In what stage of Lyme disease is erythroid chronicum seen? a. Stage 1 b. Stage 2 c. Stage 3 4. A 45 year old male sought consult because of a button-like mass on his scrotum. Patient showed that the button-like mass is a shallow ulcer with a clean base. Sexual history revealed that he has multiple sexual partners.Last sexual contact was three weeks prior to consult. Silver stain of the scrapings from the ulcer showed corkscrew-shaped bacteria. This genital ulcer is also called a/an: a. Soft chancre b. Hard chancre c. Chancroid 5. In lymphogranuloma venereum, the characteristic finding of a granulomatous inflammation associated with a stellate abscess will most likely be found in the: a. Genital papule b. Genital ulcer c. Draining lymph node ANS: PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 11 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS VI. FORMATIVE QUIZ Question & Choices Answer & Rationale Common organ involved in isolated organ tuberculosis → M. tuberculosis will cause tuberculous meningitis 1. The organs most commonly involved in isolated Not a common organ involved organ tuberculosis include all of the following → Becomes infected as a result of swallowing EXCEPT: expectorated infected material or through lymphatic B dissemination A. Meninges B. Larynx Common organ involved in isolated organ tuberculosis C. Kidneys → M. tuberculosis will cause renal tuberculosis D. Bone Common organ involved in isolated organ tuberculosis → M. tuberculosis will cause tuberculous osteomyelitis Hard chancre Causes granuloma inguinale Causes lymphogranuloma venereum Chancroid (soft chancre) is a genital ulcer caused by H. ducreyi. → An acute ulcerative sexually transmitted infection → Starts as a papule which becomes ulcerated, forming a 2. The causative agent of chancroid is: tender and genital ulcer → Chancroid on the mons pubis of a female: A. Treponema pallidum ○ Base of ulcer: yellow, shaggy exudate D B. Klebsiella granulomatis C. Chlamydia trachomatis D. Haemophilus ducreyi 💬💬Caused A. Also known as chancroid by H. ducreyi B. 💬 Genital ulcer caused by Treponema pallidum 💬 Lesion starts as papule → ulcerated, forming a shallow clean base ulcer (margins are hard or indurated) 💬 → “Button like” mass Hard chancre of Syphilis → Site of treponemal invasion 3. Identify the genital ulcer caused by Treponema pallidum: A. Soft chancre B B. Hard chancre C. Eschar D. Chagoma C.💬 Seen in cutaneous anthrax caused by B. anthracis D.💬 Caused by T. cruzi PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 12 of 13 PATHOLOGY | LE 2 Infectious Diseases 1: Bacterial Infections II | DR. ARLENE SANTOS Leprae cells are lipid-laden macrophages which are seen in lepromatous leprosy. Skin lesions that have no granuloma in contrast to skin lesions of tuberculoid leprosy. 4. Lepra cells are microscopic findings seen in lesions of: A A. Lepromatous leprosy B. Tuberculoid leprosy In a normal smear, the RBC is 2⁄3 the size of a lymphocyte. In EBV Infection: (+) atypical lymphocytes. They are atypical because the lymphocytes are larger with more cytoplasm, with an oval, indented or folded nucleus. The cytoplasm tends to be indented by the surrounding RBCs. 5. Which of the following is the characteristic microscopic finding seen in the peripheral smear of a patient with Epstein-Barr virus Infection? A. Toxic granules B B. Atypical lymphocytes C. Hypersegmented neutrophils with 5 or more nuclear lobes D. Macro-ovalocytes 6. The components of Hutchinson’s triad include all of the following EXCEPT: Hutchinson’s triad includes interstitial keratitis, eighth nerve deafness and hutchinson teeth which refers to small incisors w/ A. Hutchinson teeth D notches in the enamel resembling peg cells or screwdriver. B. Eight nerve deafness C. Interstitial keratitis D. Frontal bossing PATHOLOGY Infectious Diseases 1: Bacterial Infections II PAGE 13 of 13