Differentials
Syphilis (Treponema pallidum)
SIGNS / SYMPTOMS
Syphilis is in the differential with the presentation of a genital ulcer; however, the primary chancre caused by syphilis differs by its indurated margins, and the associated inguinal lymphadenopathy is usually bilateral and nontender.
INVESTIGATIONS
A rapid plasma reagin or Venereal Disease Research Laboratory test with a confirmatory fluorescent treponemal antibody absorbed test should always be sent as part of a diagnostic work-up for LGV. Dark field microscopy from the swab of a primary syphilitic chancre may also reveal treponemes.[35]
Gonococcal proctitis
SIGNS / SYMPTOMS
Particularly in women and men who have sex with men who report a history of receptive anal intercourse, gonococcus is frequently cotransmitted, and though frequently asymptomatic, the acute presentation is very similar to LGV in early stages of proctitis, but LGV progresses to late stages marked by granulomatous inflammation, strictures, and chronic ulcerations.[36]
INVESTIGATIONS
Diagnosis can be made with swab sent for culture, Gram stain, nucleic acid amplification test, or DNA probe for Neisseria gonorrhoeae.
Genital herpes (HSV)
SIGNS / SYMPTOMS
HSV usually presents as painful vesicles that ulcerate; whereas LGV primary ulcers are painless. Genital herpes is also usually associated with bilateral inguinal lymphadenopathy, as opposed to LGV, which tends to be unilateral.
INVESTIGATIONS
Clinical diagnosis can be confirmed by swabbing lesions for HSV culture or HSV polymerase chain reaction (PCR).[30]
Mpox
SIGNS / SYMPTOMS
Patients typically present with a characteristic vesiculopustular rash that progresses in sequential stages that may involve the palms and soles. Prodromal symptoms may include fever, lymphadenopathy, backache, and myalgia. In the 2022-2023 clade II mpox outbreak, rash lesions were atypical, often localized to the genital, perineal/perianal, or perioral areas and not spreading further.
INVESTIGATIONS
Polymerase chain reaction of skin lesion material: positive for mpox or Orthopoxvirus DNA.
Chancroid
SIGNS / SYMPTOMS
Chancroid differs from LGV by the predominance of multiple painful papules that rapidly become pustular and exudative.
INVESTIGATIONS
Gram stain (with Gram-negative rods in a pattern referred to as "school of fish") and culture for Haemophilus ducreyi are often helpful but the specificity and yield are poor. Polymerase chain reaction assays are available.[30]
Granuloma inguinale/donovanosis (Klebsiella granulomatis)
SIGNS / SYMPTOMS
Similar to LGV, ulcerative lesions are painless, but granuloma inguinale spreads subcutaneously and usually progress without true lymphadenitis. Genital lesions are highly vascular, tend to be very friable and coalesce.
INVESTIGATIONS
Definitive diagnosis requires visualization of dark-staining, Donovan bodies on tissue preparation or biopsy. Routine isolation by culture is difficult.[30]
Filariasis
SIGNS / SYMPTOMS
Lymphatic filariasis is in the differential for inguinal lymphadenopathy presenting in endemic regions; however, pruritus and cutaneous manifestations in the extremities suggest parasitic infection rather than LGV.
INVESTIGATIONS
Microfilariae that cause lymphatic filariasis can be detected in blood. Nocturnally periodic microfilariae can be provoked into the blood circulation during the daytime with a dose of diethylcarbamazine if blood testing at night is unfeasible.
Cat-scratch disease (Bartonella henselae)
SIGNS / SYMPTOMS
Though regional lymphadenopathy is the most characteristic manifestation of cat-scratch disease, most patients will report a history of recent contact with a kitten.
INVESTIGATIONS
Diagnosis may be confirmed by polymerase chain reaction from a lymph node, but in combination with clinical findings, serologic testing is the initial test of choice.[37]
Tularemia (Francisella tularensis)
SIGNS / SYMPTOMS
Tularemia is usually transmitted by tick or animal exposure. Depending on the portal of entry, tularemia may present as an ulceroglandular syndrome, but the primary skin lesion is a papule that necroses and leaves behind a painful ulcer. Regional lymphadenopathy may precede, coincide or follow this. In LGV, lymphadenopathy appears after the primary ulcer, which is painless and recedes.
INVESTIGATIONS
F tularensis can occasionally be isolated from blood, lymph nodes or wounds, but because of the danger to laboratory personnel and its potential use as an agent of bioterrorism, laboratory personnel should be cautioned if suspected. Rapid diagnostic tests are available by serologic and polymerase chain reaction assays.[38]
Bubonic plague (Yersinia pestis)
SIGNS / SYMPTOMS
Patients with an inguinal bubo due to plague will usually be acutely ill. Buboes tend to develop rapidly with exquisite tenderness.
INVESTIGATIONS
Y pestis may be isolated by culture from blood or swabs of skin lesions. Because of the danger to laboratory personnel and its potential use as an agent of bioterrorism, laboratory personnel should be cautioned if suspected. Serologic tests are available in patients suspected, but who have negative cultures.[39]
TB (Mycobacterium tuberculosis or disseminated Mycobacterium avium complex)
SIGNS / SYMPTOMS
LGV and tuberculosis (TB) share the propensity for the formation of chronic sinuses, especially in HIV-positive patients, when extrapulmonary TB may present with genitourinary, gastrointestinal involvement or as lymphadenitis (scrofula). Usually systemic mycobacterial infections are associated with hematogenous spread and constitutional symptoms.
INVESTIGATIONS
A tuberculin test, or purified protein derivative, is usually positive. Biopsy with acid-fast stains of surgical specimens and/or culture is required for definitive diagnosis.
Amebiasis (Entamoeba histolytica)
SIGNS / SYMPTOMS
In men who have sex with men presenting with proctocolitis in endemic regions, E histolytica infection may resemble LGV.[40] Prominent signs and symptoms of invasive disease include diarrhea, dysentery, and heme-positive stool.
INVESTIGATIONS
Diagnosis of amebic proctocolitis is made by recovery of parasites in the stool.
Lymphoma
SIGNS / SYMPTOMS
Lymphoma will usually be associated with constitutional symptoms and generalized lymphadenopathy.
INVESTIGATIONS
Diagnosis of lymphoma is made by histopathology from a lymph node biopsy.
Incarcerated inguinal hernia
SIGNS / SYMPTOMS
Differential for an inguinal mass. Hernia most often can be identified by physical exam and maneuvers to reduce the hernia.
INVESTIGATIONS
CT scan may be helpful to assess the pelvic anatomy.
Inflammatory bowel disease
SIGNS / SYMPTOMS
Differential for proctocolitis. LGV is generally confined to the distal sigmoid colon and rectum, whereas Crohn disease may present anywhere in the gastrointestinal tract.[24]
INVESTIGATIONS
Distinction should be made by performing polymerase chain reaction for Chlamydia trachomatis on rectal swab specimen or biopsy.
Cytomegalovirus (CMV) colitis
SIGNS / SYMPTOMS
Differential for proctocolitis in patients with HIV/AIDS. LGV is generally confined to the distal sigmoid and rectum.[41]
INVESTIGATIONS
Histopathology obtained with proctosigmoidoscopy may help distinguish CMV. Polymerase chain reaction from the serum should also detect a high level viremia.
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