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AUTHOR AND EDITOR INFORMATION

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Author: Clara-Dina Cokonis, MD, Staff Physician, Department of Medicine, Division of Dermatology, Cooper Hospital University Medical Center

Clara-Dina Cokonis is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Medical Association

Coauthor(s): Steven M Manders, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania; Associate Professor, Department of Internal Medicine, Division of Dermatology, University of Medicine and Dentistry of New Jersey; Kari Williamson Boucher, MD, Staff Physician, Department of Internal Medicine, Division of Dermatology, University of Medicine and Dentistry of New Jersey

Editors: James J Nordlund, MD, Professor Emeritus, Department of Dermatology, University of Cincinnati College of Medicine; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

Author and Editor Disclosure

Synonyms and related keywords: GI, sexually transmitted disease, STD, venereal disease, VD, Donovan bodies, donovanosis, genital lesions, Calymmatobacterium granulomatis, C granulomatis, Klebsiella granulomatis, Donovania granulomatis, K granulomatis, D granulomatis

INTRODUCTION

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Background

Granuloma inguinale (GI) is primarily a sexually transmitted disease in which characteristic intracellular inclusions called Donovan bodies may be seen. It usually manifests as genital lesions, which are indolent, progressive, ulcerative, and granulomatous.

Pathophysiology

GI is caused by the gram-negative pleomorphic bacillus Klebsiella granulomatis, which is formerly known as Calymmatobacterium granulomatis or Donovania granulomatis. The mode of transmission is primarily through sexual contact, although GI may be obtained through a fecal route or by passage through an infected birth canal. It is considered to be only mildly contagious, and repeated exposure may be necessary for clinical infection to occur.

Frequency

United States

Fewer than 100 cases are reported annually, many of which are thought to be due to foreign travel.

International

GI is endemic in Western New Guinea, the Caribbean, Southern India, South Africa, Southeast Asia, Australia, and Brazil.

Mortality/Morbidity

Untreated, the disease will most likely not remit, and the lesions may continue to expand for years (see Complications).

Race

The racial predilection is most likely due to socioeconomic status and living conditions rather than a racial susceptibility.

  • The incidence is higher in blacks than in whites in the United States.
  • The incidence is higher in natives than in Europeans in Western New Guinea.
  • The incidence is higher in Hindus than in Moslems in India.

Sex

No sexual predominance exists.

Age

The highest incidence occurs in persons aged 20-40 years.


CLINICAL

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History

The incubation period may range from 1 week to 3 months.

Physical

  • Morphology
    • Four varieties of skin lesions occur.
      • Ulcerovegetative type (most common): These lesions develop from the nodular type and consist of large, usually painless, spreading, exuberant ulcers. The ulcers have clean, friable bases with distinct, raised, rolled margins. The ulcers are typically beefy red in appearance and bleed easily (see Media File 1). Autoinoculation is a common feature, resulting in lesions on adjacent skin.
      • Nodular type: Soft, often pruritic, red nodules arise at the site of inoculation and eventually ulcerate and present a bright red granulating surface. (A nodule may be mistaken for a lymph node [a pseudobubo].)
      • Cicatricial type: Dry ulcers evolve into cicatricial plaques and may be associated with lymphedema.
      • Hypertrophic or verrucous type (relatively rare): This proliferative reaction with formation of large vegetating masses may resemble genital warts.
    • Elephantiasislike swelling of the external genitalia is frequent in later-stage lesions.
  • Distribution
    • In men, lesions may occur on the penis, the scrotum, and/or the glans.
    • In women, lesions may occur on the labia minora, the mons veneris, the fourchette, and/or the cervix. Cervical involvement occurs in 10% of cases.
  • Extragenital involvement
    • Lymphadenopathy does not occur due to GI, but lymph node enlargement due to secondary bacterial infection or pseudobuboes may occur. Extragenital involvement occurs in 6% of cases.
    • Autoinoculation or direct extension may lead to involvement of the oral cavity and the gastrointestinal tract.
    • Hematogenous dissemination to the spleen, the lungs, the liver, the bones, and the orbits may occur and occasionally results in death.

Causes

GI is caused by K granulomatis, a gram-negative pleomorphic bacillus formerly known as C granulomatis.


DIFFERENTIALS

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Lymphogranuloma Venereum
Syphilis

Other Problems to be Considered

Mycobacterial infection


WORKUP

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Lab Studies

  • Although isolation of K granulomatis has been reported, the organism is extremely fastidious and culture is beyond the capability of most laboratories. The most effective method of establishing a diagnosis is direct visualization of the organisms within the macrophages as bipolar staining, safety pin–shaped intracytoplasmic inclusions, known as Donovan bodies. Tissue crush preparations are the most reliable method of establishing a diagnosis, although the organism can occasionally be visualized in biopsy specimens.
    • Tissue should be obtained from the ulcer edge or base via punch biopsy, curettage, or a thin wedge. Next, the tissue is crushed between 2 glass slides, separated, and then air dried. A Wright-Giemsa, Warthin-Starry, or Leishman stain may be used to demonstrate the Donovan bodies.
    • The organisms may be difficult to find in early or secondarily infected lesions or in sections stained with hematoxylin and eosin (H&E). Thin, plastic-embedded sections stained with Giemsa or silver may allow identification of the rod-shaped encapsulated organisms within the macrophages.
    • If quick staining is necessary, a smear can be performed. First, a cotton swab is gently rolled over the ulcer as not to cause bleeding. The swab is then rolled over a glass slide. The slide is allowed to air dry and then stained with Giemsa or pinacyanol to demonstrate Donovan bodies.
  • Polymerase chain reaction techniques demonstrate K granulomatis; however, it is currently only used for scientific research.
  • An indirect immunofluorescent technique is available to test serum; however, it is not accurate enough for confirmatory diagnosis.
  • Culture of K granulomatis from feces has been reported using a monocyte co-culture system and a modified Chlamydia culture.
  • Papanicolaou smears may identify Donovan bodies in patients undergoing routine cervical cytological screening.

Imaging Studies

  • If bony involvement is suspected, radiography or other imaging studies are indicated.

Other Tests

  • Testing for other sexually transmitted diseases is warranted because multiple coexisting infections are not uncommon.

Histologic Findings

The epidermis displays acanthosis at the ulcer edge, with pseudoepitheliomatous hyperplasia variably present. A dense dermal infiltrate of histiocytes and plasma cells is present, with a scattering of small neutrophilic abscesses. The macrophages are large and vacuolated, and they may demonstrate intracellular bacilli (ie, Donovan bodies) when prepared with a Warthin-Starry, Wright-Giemsa, or Leishman stain. K granulomatis does not stain with hematoxin and eosin.


TREATMENT

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Medical Care

The recommended antibiotic is either trimethoprim/sulfamethoxazole1 or doxycycline. Alternatives include ciprofloxacin, erythromycin, or azithromycin.2 The antibiotic should be given for at least a 3-week course and continued until reepithelialization of the ulcer and resolution of any signs of the disease. If the ulcers do not respond within the first days of therapy, add an aminoglycoside (eg, gentamicin 1 mg/kg IV q8h). Relapse may occur up to 18 months after treatment. Tetracycline is no longer recommended owing to bacterial resistance.

Special considerations

Pregnancy is a relative contraindication for the use of sulfonamides. In pregnant and lactating women, the Centers for Disease Control and Prevention3 recommends erythromycin with or without a parenteral aminoglycoside; however, recent data suggest erythromycin may increase the risk of congenital malformation.4 Doxycycline and ciprofloxacin are contraindicated in pregnancy.

HIV-associated GI may take longer to heal, and the addition of a parenteral aminoglycoside to the regimen is highly recommended.5

Sexual contacts within 60 days prior to the onset of the patient's symptoms of GI should be examined and offered therapy.

Surgical Care

Once healed, disfiguring genital swellings may need to be surgically corrected.


MEDICATION

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The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug NameTrimethoprim/sulfamethoxazole (Bactrim IV, Bactrim SS, Bactrim DS, Septra)
DescriptionSulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid. Trimethoprim reversibly inhibits dihydrofolate reductase and blocks the production of tetrahydrofolic acid from dihydrofolic acid.
Adult DoseOne DS tab (800 mg/160 mg) PO bid for at least 3 wk
Pediatric Dose<2 months: Contraindicated
>2 months: 15-20 mg/kg/d (based on TMP) PO divided q6-8h for at least 3 wk
ContraindicationsDocumented hypersensitivity; megaloblastic anemia due to folate deficiency; pregnant patients; nursing mothers; age <2 mo
InteractionsMay increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration of diuretics, primarily thiazides, increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; sulfonamides may increase free methotrexate concentrations; TMP-SMZ may interfere with Jaffe alkaline picrate reaction for creatinine, causing overestimation of creatinine value
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDiscontinue at first appearance of skin rash or sign of adverse reaction; Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have rarely occurred; pseudomembranous colitis caused by Clostridium difficile has been reported; sulfonamide hypersensitivity reactions may cause cough, shortness of breath, and pulmonary infiltrates
Give with caution to patients with impaired renal or hepatic function, possible folate deficiency (elderly, alcoholic, anticonvulsant therapy, malabsorption, malnutrition) and those with severe allergies or bronchial asthma; dose-related hemolysis may occur in patients with G-6-PD deficiency
Obtain CBC count frequently and discontinue therapy if significant hematologic changes occur; may cause bone marrow suppression (if signs occur, give 5-15 mg/d leucovorin); patients with AIDS may not tolerate or respond to TMP-SMZ in same manner as non-AIDS patients; give fluids to prevent crystalluria and stone formation

Drug NameDoxycycline (Adoxa, Doryx, Vibramycin, Periostat)
DescriptionBacteriostatic tetracycline antibiotic that inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose100 mg PO bid for at least 3 wk
Pediatric Dose<8 years: Not recommended
>8 years and <45 kg: 2.2 mg/kg PO/IV bid for at least 3 wk; not to exceed 200 mg/d
>8 years and >45 kg: 100 mg PO bid for at least 3 wk
ContraindicationsDocumented hypersensitivity
InteractionsBioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; depresses plasma prothrombin activity (anticoagulant dosage may need to be decreased); decreases effect of penicillin; barbiturates, carbamazepine, and phenytoin decrease half-life; concurrent use with methoxyflurane has resulted in fatal renal toxicity; concurrent use with oral contraceptives may render them less effective
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsPhotosensitivity may occur with prolonged exposure to sunlight or tanning equipment; caution in patients with hepatic or renal insufficiency; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; as with all antibiotics, risk of superinfection exists; bulging fontanels in infants and benign intracranial hypertension in adults may occur (these resolve upon discontinuation)

Drug NameCiprofloxacin (Cipro)
DescriptionBactericidal fluoroquinolone antibiotic that inhibits the bacterial enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Adult Dose750 mg PO bid for at least 3 wk
Pediatric Dose<18 years: Not recommended
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity; use with tizanidine
InteractionsMultivalent cation-containing products such as magnesium/aluminum antacids, sucralfate, didanosine, other highly buffered drugs or products containing calcium, iron, or zinc may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; phenytoin serum levels may be altered (increased or decreased); probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, tizanidine, glyburide, methotrexate, cyclosporine, and digoxin (monitor theophylline and digoxin levels); may increase effects of warfarin (monitor PT); metoclopramide accelerates absorption of oral ciprofloxacin; NSAIDs (but not acetyl salicylic acid) with very high doses of fluoroquinolones may provoke convulsions
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIn prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections with drug-resistant bacteria may occur with prolonged or repeated antibiotic therapy; avoid excessive sunlight due to risk of phototoxicity; crystalluria may occur if urine is alkaline or concentrated; CNS may be affected, resulting in nervousness, agitation, insomnia, anxiety, nightmares, or paranoia

Drug NameErythromycin (E-Mycin, Ery-Tab, Eryc)
DescriptionMacrolide antibiotic that inhibits bacterial protein synthesis by binding to 50S ribosomal subunits of susceptible organisms; may be bacteriocidal or bacteriostatic depending on concentration and type of microorganism.
Adult Dose500 mg PO qid for at least 3 wk
Pediatric Dose30-50 mg/kg/d PO divided q6-8h for at least 3 wk
ContraindicationsDocumented hypersensitivity; coadministration of terfenadine, astemizole, pimozide, or cisapride
InteractionsCoadministration may increase toxicity of theophylline and digoxin; may potentiate anticoagulant effects of oral anticoagulants; because erythromycin is an inhibitor of cytochrome P450 3A (CYP3A), the following drug levels may rise, causing increased risk of toxicity: ergotamine, dihydroergotamine, benzodiazepines (eg, triazolam, alprazolam, midazolam), HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin), sildenafil, cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine; additional drug interactions exist with hexobarbital, phenytoin, valproate, terfenadine, and astemizole
When erythromycin was coadministered with cisapride, terfenadine, or astemizole, rare cases of serious cardiovascular adverse events, including ECG QT/QTc interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed and fatalities have been reported
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCaution with impaired hepatic function; estolate formulation may cause cholestatic jaundice; adverse gastrointestinal effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur; risk of superinfection; may aggravate weakness in patients with myasthenia gravis; possible increased risk of infantile hypertrophic pyloric stenosis in infants that have consumed erythromycin

Drug NameAzithromycin (Zithromax)
DescriptionAzalide antibiotic (subclass of macrolide antibiotics) that inhibits bacterial protein synthesis by binding 50S ribosomal subunits of susceptible organisms; may be bacteriocidal or bacteriostatic depending on concentration and type of microorganism.
Adult Dose1 g PO qwk for at least 3 wk
Pediatric Dose<16 years: Not established
>16 years: Administer as in adults
ContraindicationsKnown hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic
InteractionsEffects are reduced with coadministration of aluminum- and/or magnesium-containing antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine; coadministration with nelfinavir may effect a levels of both drugs (no dosage adjustment required but monitoring for azithromycin toxicity is warranted, ie, liver enzyme abnormalities and hearing impairment); efavirenz may increase peak plasma concentrations
Monitor theophylline level and PT when coadministered with theophylline and warfarin, respectively, because pharmacokinetics have not been determined; azithromycin studies with the following drugs have not been performed; however, interactions with other macrolides have been established: digoxin, ergotamine, dihydroergotamine, triazolam, carbamazepine, cyclosporine, hexobarbital, and phenytoin
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsSite reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function; caution advised in patients with renal impairment (azithromycin not tested in this population); because other macrolides may prolonged cardiac repolarization and QT interval, causing cardiac arrhythmia and torsades de pointes (possible that azithromycin may have similar effect)


FOLLOW-UP

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Complications

  • The most serious complication is carcinoma, which is reported to occur in 0.25% of patients. This includes squamous and basal cell carcinomas. Of note, squamous cell carcinoma is sometimes difficult to distinguish from donovanosis histologically.
  • Once the lesions have healed, extensive fibrosis, stricture formation, and phimosis, leading to significant deformity and functional disability, may occur.
  • Elephantiasis of the genitals may occur secondary to lymphatic destruction.
  • GI may also progress to involve extragenital sites with potentially fatal systemic spread to the viscera.

Prognosis

  • Relapse may occur up to 18 months after treatment.
  • If untreated, the lesions may continue to expand for years.

Patient Education


MISCELLANEOUS

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Special Concerns

  • Pregnancy and HIV-associated GI are special concerns in the treatment of this condition. The addition of a parenteral aminoglycoside (eg, gentamicin) to the treatment regimen should be considered for pregnant women and for persons with HIV-associated GI (see Medical Care).


MULTIMEDIA

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Media file 1:  Beefy-red penile ulcers.
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Media type:  Photo

Media file 2:  Courtesy of Hon Pak, MD.
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Media type:  Photo

Media file 3:  Courtesy of Hon Pak, MD.
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Media type:  Photo

Media file 4:  Courtesy of Hon Pak, MD.
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Media type:  Photo


REFERENCES

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  1. Sulfamethoxazole and trimethoprim [package insert]. Irvine, Calif: Sicor Pharmaceuticals; 2003.
  2. Bowden FJ, Savage J. Azithromycin for the treatment of donovanosis. Sex Transm Infect. Feb 1998;74(1):78-9. [Medline].
  3. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. May 10 2002;51(RR-6):1-78. [Medline].
  4. Källén BA, Otterblad Olausson P, Danielsson BR. Is erythromycin therapy teratogenic in humans?. Reprod Toxicol. Jul-Aug 2005;20(2):209-14. [Medline].
  5. Manders SM, Baxter JD. Granuloma inguinale and HIV: a unique presentation and novel treatment regimen. J Am Acad Dermatol. Sep 1997;37(3 Pt 1):494-6. [Medline].
  6. Buntin DM, Rosen T, Lesher JL Jr, Plotnick H, Brademas ME, Berger TG. Sexually transmitted diseases: bacterial infections. Committee on Sexually Transmitted Diseases of the American Academy of Dermatology. J Am Acad Dermatol. Aug 1991;25(2 Pt 1):287-99. [Medline].
  7. Fiumara NJ, Demis DJ, eds. Donovanosis. In: Clinical Dermatology. Vol 3. Philadelphia, Pa: JB Lippincott; 1999:Section 16, Unit 21.
  8. Hart G. Donovanosis. Clin Infect Dis. Jul 1997;25(1):24-30; quiz 31-2. [Medline].
  9. James WD. Granuloma inguinale. In: Textbook of Military Medicine. Walter Reed AMC: Washington, DC; 1994:519-21.
  10. Lucas S. Bacterial diseases. In: Elder DE, ed. Lever's Histopathology of the Skin. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:580-1.
  11. O'Farrell N. Donovanosis. Sex Transm Infect. Dec 2002;78(6):452-7. [Medline].
  12. Richens J. Donovanosis (granuloma inguinale). Sex Transm Infect. Dec 2006;82 Suppl 4:iv21-2. [Medline].
  13. Rothenberg RB. Granuloma inguinale. In: Fitzpatrick's Dermatology in General Medicine. Vol 2. 6th ed. New York, NY: McGraw-Hill; 2003:2201-5.
  14. ThomasHealthcare. Physicians' Desk Reference. PDR.net. Available at http://www.pdr.net/Home/Home.aspx. Accessed 2005.

Granuloma Inguinale (Donovanosis) excerpt

Article Last Updated: Nov 1, 2007