Donovanosis =الحبيبوم المغبني=الداء الدونوفاني |
Donovanosis Granuloma inguinale is a chronic bacterial infection that frequently is associated with other sexually transmitted diseases. Granuloma inguinale is characterized by intracellular inclusions in macrophages referred to as Donovan bodies. Granuloma inguinale usually affects the skin and mucous membranes in the genital region, where it results in nodular lesions that evolve into ulcers. The ulcers progressively expand and are locally destructive
The intracellular organism responsible for granuloma inguinale was initially described by Donovan over a century ago, and subsequently, the bacterium was classified in 1913 as Calymmatobacterium granulomatis. Although Anderson suggested that the organism be eponymously named Donovania granulomatosis, Carter et al discovered that the molecular structure of the causative organism was similar to Klebsiella species and reclassified the gram-negative pleomorphic bacillus as Klebsiella granulomatis.1,2 The mode of transmission of granuloma inguinale primarily occurs through sexual contact; however, it is hypothesized to have low infectious capabilities because repeated exposure is necessary for clinical infection to occur. Additionally, granuloma inguinale may also be obtained through the fecal route or by passage through an infected birth canal.
HistoryAlthough the exact incubation period for granuloma inguinale is unknown, it ranges from a day to a year, with the median time being 50 days.3 PhysicalMorphology
CausesGranuloma inguinale is caused by Klebsiella granulomatis, a gram-negative pleomorphic bacillus formerly known as Calymmatobacterium granulomatis. Laboratory Studies
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Histologic FindingsThe 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 contain intracellular bacilli (ie, Donovan bodies), which are best visualized using special stains such as a Warthin-Starry, Wright-Giemsa, or Leishman stain. Klebsiella granulomatis does not stain well with hematoxylin and eosin. Laboratory Studies
Imaging Studies
Other Tests
Histologic FindingsThe 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 contain intracellular bacilli (ie, Donovan bodies), which are best visualized using special stains such as a Warthin-Starry, Wright-Giemsa, or Leishman stain. Klebsiella granulomatis does not stain well with hematoxylin and eosin.
Medical CareThe recommended antibiotic for granuloma inguinale is either trimethoprim/sulfamethoxazole7 or doxycycline. Alternatives include ciprofloxacin, erythromycin, or azithromycin.8 The antibiotic should be given for at least a 3-week course and continued until reepithelialization of the ulcer occurs and any signs of the disease have resolved. If the granuloma inguinale ulcers do not respond within the first days of therapy, add an aminoglycoside (eg, gentamicin at 1 mg/kg IV q8h). Relapse of granuloma inguinale may occur up to 18 months after treatment. In some countries, tetracycline is no longer recommended, owing to bacterial resistance.9 Surgical CareOnce granuloma inguinale is healed, disfiguring genital swellings may need to be surgically corrected.
MedicationThe goal of pharmacotherapy for granuloma inguinale is to reduce morbidity and to prevent complications. AntibioticsEmpiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Trimethoprim/sulfamethoxazole (Bactrim IV, Bactrim SS, Bactrim DS, Septra)Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid. Trimethoprim reversibly inhibits dihydrofolate reductase and blocks the production of tetrahydrofolic acid from dihydrofolic acid. May 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 Documented hypersensitivity; megaloblastic anemia due to folate deficiency; pregnant patients; nursing mothers; age <2 mo 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 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 Doxycycline (Adoxa, Doryx, Vibramycin, Periostat)Bacteriostatic tetracycline antibiotic that inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Adult100 mg PO bid for at least 3 wk Pediatric<8 years: Not recommended Bioavailability 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 Documented hypersensitivity 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) Ciprofloxacin (Cipro)Bactericidal 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. Adult750 mg PO bid for at least 3 wk Pediatric<18 years: Not recommended Multivalent 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 Documented hypersensitivity; use with tizanidine 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 Erythromycin (E-Mycin, Ery-Tab, Eryc)Macrolide 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. Adult500 mg PO qid for at least 3 wk Pediatric30-50 mg/kg/d PO divided q6-8h for at least 3 wk Coadministration 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 Documented hypersensitivity; coadministration of terfenadine, astemizole, pimozide, or cisapride 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; 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 Azithromycin (Zithromax)Azalide 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. |