What infectious diseases are known as great masqueraders due to their ability to mimic many other diseases and affect multiple systems?

Infectious Diseases Known as "Great Masqueraders"

Syphilis is the classic "great masquerader" among infectious diseases, followed by tuberculosis, Lyme disease, and myasthenia gravis (though autoimmune rather than infectious), all capable of mimicking diverse conditions across multiple organ systems. 1, 2, 3

Primary Great Masqueraders

Syphilis - The Original Great Imitator

• Syphilis holds the distinction as the oldest and most notorious "great masquerader," presenting with multitudinous mucocutaneous manifestations and affecting virtually any organ system. 3, 4
• The infection demonstrates tropism for various organ systems including neurological, cardiovascular, dermatological, and oral manifestations. 3, 4
• Clinical presentations are highly variable and non-specific across primary, secondary, and tertiary stages, making diagnosis particularly challenging. 4
• Oral cavity involvement is common in early stages, with presentations ranging from single chancres to diverse secondary lesions that can mimic benign oral pathology. 4
• Ocular manifestations include optic disc edema that can be mistaken for papilledema, along with visual disturbances. 3
• Systemic symptoms may include non-scarring alopecia (particularly frontal marginal hairline), arthralgias, weight loss, and headaches. 3

Tuberculosis - The Second Great Imitator

• Tuberculosis is described as "the second great imitator" due to its ability to mimic various disease processes, particularly in extrapulmonary presentations. 2, 5
• Extrapulmonary tuberculosis (EPTB) constitutes 15-20% of cases in immunocompetent patients and exceeds 50% in HIV-positive individuals. 2
• TB can present at unusual anatomical sites without evidence of systemic or pulmonary involvement, requiring high clinical suspicion. 2
• Pott disease (vertebral tuberculosis) represents a classic yet diagnostically challenging manifestation, particularly in low-burden regions. 5
• Clinical presentations range from altered mental status with pleural effusions to extensive vertebral destruction with psoas abscesses. 5

Myasthenia Gravis - The Neuromuscular Masquerader

• Myasthenia gravis is specifically termed "the great masquerader" in ophthalmology because it can mimic many types of incomitant strabismus with or without ptosis. 1, 6
• This B-cell mediated autoimmune disorder affects the neuromuscular junction, causing variable weakness exacerbated by fatigue. 1, 6
• Ocular presentations include fluctuating diplopia, variable strabismus, and ptosis that worsen throughout the day. 1, 6
• Extraocular muscles are particularly susceptible due to their twitch fiber composition and fewer acetylcholine receptors. 1, 6
• Acetylcholine receptor antibodies are present in nearly all generalized cases but only 40-77% of purely ocular cases. 1, 6

Additional Masquerading Infections

Fungal Infections

• Multiple fungal infections commonly mimic tuberculosis, creating diagnostic confusion and treatment delays. 7
• Aspergillosis (particularly chronic and allergic bronchopulmonary forms) represents the most frequently misdiagnosed fungal infection, with over 100 cases in India and Pakistan receiving anti-TB therapy before correct diagnosis. 7
• Histoplasmosis, blastomycosis, cryptococcosis, talaromycosis, coccidioidomycosis, mucormycosis, sporotrichosis, phaeohyphomycosis, and chromoblastomycosis all present with TB-like symptoms. 7
• Among 80 documented misdiagnosed cases, mortality reached 33.8%, emphasizing the critical importance of accurate diagnosis. 7

Lyme Disease

• Lyme disease is recognized as another classic "great imitator" with multisystem manifestations. 2

Nocardiosis

• Nocardiosis joins the list of infectious diseases capable of mimicking diverse clinical presentations. 2

Critical Diagnostic Pitfalls

Common Misdiagnosis Patterns

• Fungal infections and tuberculosis are frequently confused, with patients receiving prolonged anti-TB therapy before correct fungal diagnosis, resulting in preventable mortality. 7
• Syphilis can present with isolated symptoms (alopecia, ocular findings) without classic manifestations, delaying recognition. 3
• Myasthenia gravis may be missed when patients present with variable diplopia patterns that don't fit typical cranial nerve palsies. 1, 6

Key Diagnostic Approaches

• For suspected syphilis: obtain rapid plasma reagin (RPR) with confirmatory treponemal testing; cerebrospinal fluid analysis if neurological symptoms present. 3
• For tuberculosis at unusual sites: utilize histopathology (57.5% diagnostic yield), culture (52.5%), and ancillary techniques including Ziehl-Neelsen staining. 2
• For fungal infections: employ histopathology, culture, serology, and molecular methods (gene sequencing) rather than empiric anti-TB treatment. 7
• For myasthenia gravis: assess for fluctuating weakness worsening with fatigue, improvement with rest, and consider ice pack test; refer to neurology for acetylcholine receptor antibody testing. 1, 6

High-Risk Populations Requiring Increased Vigilance

• HIV-positive patients show dramatically increased rates of extrapulmonary tuberculosis (>50% vs 15-20%). 2
• Patients with autoimmune thyroid disease or thymoma have elevated myasthenia gravis risk. 1, 6
• Immunocompromised patients demonstrate higher rates of atypical fungal presentations. 7