Donovanosis

Overview

Definition

Donovanosis, or granuloma inguinale, is an STD characterized by chronic progressive ulcers affecting the genital region.

Epidemiology

• Rare in the United States
• Generally, incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is declining worldwide, partly due to the focus on HIV HIV Anti-HIV Drugs prevention and the role genital ulcers play in the disease’s transmission.
• Most occurrences are in the following areas:
  • Papua New Guinea
  • Southern Africa
  • French Guiana
  • India
  • Caribbean and Brazil
  • Aboriginal communities in Australia

Etiology

• Caused by Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella granulomatis (formerly Calymmatobacterium granulomatis):
  • Gram-negative bacterium
  • Encapsulated Encapsulated Klebsiella
  • Facultative aerobe
  • Intracellular
• Risk factors include:
  • Poor genital hygiene (uncircumcised men)
  • Unprotected sexual intercourse (especially between men)
  • Low socioeconomic status

Pathophysiology

• After inoculation → painless papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes or nodule Nodule Chalazion → due to high vascularity, a classic “beefy-red” lesion develops
• Minimal trauma leads to ulcerative formation, without lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy.
• Eventually, the lesion progressively grows outward, with borders developing a “snake-like” appearance.

Clinical Presentation

Signs and symptoms

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: average of 50 days (and up to a year) postinoculation 
• Transmission: sexually transmitted
• Site of lesion:
  • Majority are in the genital region.
  • Most common in men: prepuce Prepuce The double-layered skin fold that covers the glans penis, the head of the penis. Penis: Anatomy, coronal Coronal Computed Tomography (CT) sulcus, glans, and anus 
  • Most common in women: labia minora Labia minora Vagina, Vulva, and Pelvic Floor: Anatomy, cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy, and upper genital tract
  • 6% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have extragenital lesions ( lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy, pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy, larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy).
• Lesion:
  • Classic ulcerogranulomatous lesions:
    • Also known as ulcerative donovanosis
    • Most common presentation
    • Painless, expanding ulcer that bleeds easily
    • Described as a beefy-red lesion
  • Hypertrophic or verrucous ulcer:
    • Irregular edge
    • Dry texture Texture Dermatologic Examination
  • Necrotic, offensive-smelling ulcer: associated with tissue destruction
  • Sclerotic or cicatricial lesion: scar Scar Dermatologic Examination tissue
• No regional lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy

Complications

• Healing of donovanosis ulcers can leave scars or hypertrophic lesions.
• Neoplastic change: Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) may occur in long-standing untreated lesions.
• Pseudo-elephantiasis
• Polyarthritis Polyarthritis Rheumatoid Arthritis or osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
• Stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) of the urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy, vaginal, or anus

Diagnosis and Management

Diagnosis

• Causative agent is difficult to culture.
• High index of suspicion needed, especially in endemic areas
• Diagnosis is made by a microscopic examination of a tissue smear (from the ulcer), tissue crush preparation, or biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Donovan bodies: bipolar-staining cytoplasmic inclusion bodies within macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, which may have a safety-pin appearance
  • Other histologic changes:
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation with plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cell and neutrophil infiltration
    • Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers, microabscesses, and elongation Elongation Polymerase Chain Reaction (PCR) of rete ridges Rete Ridges Lentigo Maligna in the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology

Management

• Management is a prolonged course of antibiotics until re-epithelization of ulcer has occurred (minimum 3 weeks).
• Choice of antibiotics:
  • 1st line: azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides 
  • Alternatives:
    • Doxycycline
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
    • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides (if patient is pregnant)
    • Trimethoprim-sulfamethoxazole
• There is a high chance of recurrence at 6–18 months, which requires initiating antibiotics again.
• Surgical management is reserved for extensive tissue damage.
• Patient education on safe sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria is important to reduce incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be screened for other STDs.

Differential Diagnosis

• Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid: an STD caused by Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus. The disease presents with painful ulcer(s) on the genital tract ( chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid or “ soft chancre Soft chancre Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid”), which can be accompanied by painful inguinal lymphadenopathy Inguinal Lymphadenopathy Lymphadenopathy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may develop the complication of suppurative lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy. Diagnosis is clinical and with tests ruling out syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis and herpes. Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides or ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins is the treatment of choice. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and their contacts must both be treated.
• Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections: common STD caused by herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology type 1 Type 1 Spinal Muscular Atrophy or 2. Prodromal symptoms often precede clusters of painful, fluid-filled vesicles Vesicles Female Genitourinary Examination on an erythematous base. These vesicles Vesicles Female Genitourinary Examination eventually form ulcers that can coalesce. Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary Tract Infections (UTIs), and severe neuralgia can occur. The diagnosis is generally clinical but confirmed with PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) and serologic testing. Management includes antiviral Antiviral Antivirals for Hepatitis B therapy.
• Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis: an STD caused by Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema. The disease has 4 clinical stages: Primary syphilis Primary Syphilis Syphilis begins with a solitary, painless ulcer on the genitals ( chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis). Progression to secondary syphilis Secondary Syphilis Syphilis manifests as a generalized maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever, which includes the palms and soles. The development of tertiary syphilis Tertiary Syphilis Syphilis can cause severe neurologic ( neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis), cardiovascular, and/or gummatous disease. The dormant period between secondary and tertiary syphilis Tertiary Syphilis Syphilis is the latent stage Latent Stage Benign Bone Tumors.
• Lymphogranuloma venereum Lymphogranuloma venereum Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis. Chlamydial Infections ( LGV LGV Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis. Chlamydial Infections): an STD caused by 3 strains of Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have a small, self-limited genital ulcer followed by painful inguinal and/or femoral lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Diagnosis is clinical; although PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing can help, availability is limited. Management involves tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines or erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides.