Cutaneous Markers of TB, HIV, and Syphilis

I. TUBERCULOSIS - Cutaneous Markers

A. Exogenous Inoculation

• Painless brown-red papule that develops into an indurated nodule or plaque, may ulcerate - appears 2-4 weeks after inoculation
• Prominent regional lymphadenopathy at 3-8 weeks (the "primary complex")
• Occurs mainly in children on the face or extremities
• Triggered by tattooing, medical injections, nose piercing, or trauma

• Warty, hyperkeratotic verrucous papules and plaques
• Occurs on hands in adults; buttocks, knees, ankles in children
• Represents inoculation into a previously sensitized (immune) host
• Typically on the dominant hand (pathologist's/prosector's wart)

B. Endogenous Spread

• Most common form in developing countries
• Subcutaneous nodules over cervical lymph nodes (or bone/joints) that enlarge, suppurate, and ulcerate
• Draining sinuses with reddish granulation at the base
• Heals with characteristic cord-like scars - highly diagnostic

• Painful ulcers at orifices (mouth, anus, vulva, perianal) in patients with advanced organ TB
• Lesions of poor host immunity - bacilli are numerous

C. Hematogenous Spread

• Most common form of cutaneous TB in Europe
• Reddish-brown ("apple jelly") soft nodules coalescing into plaques, typically on the face (nose/cheek)
• Slow, progressive scarring; may develop squamous cell carcinoma in chronic lesions
• Hallmark histology: classic tubercles with caseation

• Widespread macules, papules, pustules, vesicles or purpura from hematogenous dissemination
• Seen in children, debilitated patients, and HIV patients
• Most frequently reported cutaneous form in HIV-infected patients

• Cold subcutaneous abscesses that ulcerate, forming sinuses
• Associated with malnutrition and poor immunity

D. Tuberculids (Hypersensitivity Reactions - High Immunity)

• Symmetric crops of 2-8 mm firm papules that become pustular or necrotic, then heal with varioliform (pox-like) scars
• Distributed on extensor extremities (elbows, knees), dorsal hands/feet, buttocks, glans penis
• Females affected 3:1; two-thirds of cases under age 30

• Lobular panniculitis presenting as tender, recurring nodules/plaques on the posterior lower calves
• Predominantly in women
• Lesions may ulcerate and heal with scarring

• Tiny lichenoid papules, usually perifollicular, grouped on the trunk
• Mostly in children with TB lymphadenitis or bone TB
• Resolves with antituberculous therapy

II. HIV - Cutaneous Markers

A. Markers of Advanced HIV/AIDS (CD4 < 200 cells/μL)

• AIDS-defining illness; caused by HHV-8
• Red-to-violaceous, brown, or pink macules/plaques/nodules
• Starts on lower extremities, face (nose tip), hard palate, or genitalia
• Lesions are typically non-tender; can involve lymph nodes and viscera
• May be the presenting manifestation of HIV

• White, corrugated, hairy plaques on the lateral aspects of the tongue (cannot be scraped off)
• Caused by EBV; marker of significant immunosuppression
• Strongly associated with HIV - often the first clinical clue

• Red-to-violaceous dome-shaped papules and nodules resembling cherry angiomas or pyogenic granulomas
• Caused by Bartonella henselae / B. quintana
• Occurs at CD4 <200 cells/μL; may mimic KS

• Widespread macules, papules, pustules in the context of HIV/AIDS
• Most common form of cutaneous TB in HIV patients

• Multiple umbilicated papules >1 cm; widespread, involving atypical sites including the face
• In immunocompetent hosts, molluscum is small and self-limited; giant/numerous lesions signal AIDS

• Extensive hyperkeratotic gray-brown plaques involving atypical locations (scalp, palms, soles)
• Millions of mites (vs 10-15 in normal scabies); highly contagious
• Minimal or absent pruritus in AIDS patients

B. Markers of Well-Controlled/Earlier HIV

• Severe, widespread, or recalcitrant seborrheic dermatitis is one of the most common early cutaneous markers of HIV
• Erythematous plaques with greasy yellow scale on nasolabial folds, scalp, eyebrows, and chest

• Reactivation of VZV; dermatomal painful vesicular rash
• Multidermatomal or recurrent episodes in a young person suggest HIV
• Seen even with well-controlled HIV

• Chronic, large, perianal or oral HSV ulcers (>1 month duration) are AIDS-defining
• More severe presentations, atypical sites

• Intensely pruritic follicular papules and pustules on the trunk and face
• CD4 typically < 300 cells/μL; characteristic feature of HIV

• Maculopapular rash on trunk/face occurring 2-4 weeks after HIV infection
• Accompanies fever, lymphadenopathy, pharyngitis - the "mono-like" seroconversion illness

• Symmetrical pruritic papules on trunk and extremities
• One of the most common HIV-associated dermatoses in sub-Saharan Africa; marker of advanced disease

III. SYPHILIS - Cutaneous Markers (by Stage)

Primary Syphilis

• Painless, indurated, clean-based ulcer with raised rolled edges at the site of inoculation
• Appears 10-90 days (average 3 weeks) after exposure
• Single lesion in >90%; on genitalia, anal canal, lips, or fingers
• Accompanied by non-tender regional lymphadenopathy ("satellite bubo")
• Heals spontaneously in weeks even without treatment
• Darkfield microscopy of the chancre base is the gold standard

Secondary Syphilis (1-2 months after primary)

• Generalized, symmetric maculopapular rash
• Characteristically involves palms and soles (pathognomonic clue)
• Non-pruritic; salmon-pink to reddish-brown in color

• Flat, moist, broad-based, warty papules in the genital/perianal area and intertriginous regions
• Highly infectious (spirochetes on darkfield); must be distinguished from HPV condylomata acuminata
• Condyloma lata = flat and moist; condylomata acuminata = cauliflower-like and dry

• Painless, grayish-white, shallow erosions on oral/genital mucosa ("snail track ulcers")
• Highly infectious

• Patchy, non-scarring hair loss - classically described as moth-eaten pattern
• Involves scalp, eyebrows, eyelashes, beard

• Papules at the angles of the mouth

• Malaise, low-grade fever, sore throat accompany the skin lesions

Tertiary Syphilis (15-30 years later)

• Soft, granulomatous nodules that can develop anywhere on skin, mucosa, or internal organs
• Central necrosis with "gummatous" material; can destroy tissue (bones, palate, nasal septum)
• Skin gummas ulcerate with a "punched-out" appearance

Congenital Syphilis (Cutaneous Features)

• Rhinitis ("snuffles") - first sign
• Vesiculobullous eruption (pemphigus syphiliticus), especially on palms and soles
• Maculopapular rash involving palms and soles
• Saddle nose, rhagades (perioral fissures), Hutchinson's teeth - late stigmata

Summary Table