What is the most likely causative agent of a rash in a patient with a recent viral-like illness and fever, who presents with a progressive centrifugal spreading macular rash, desquamation on the chest and tongue, fever, and a positive Nikolsky sign?

Mycoplasma pneumoniae is the Most Likely Causative Agent

The clinical presentation of a positive Nikolsky sign with desquamation following a viral-like prodrome strongly suggests Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and among the listed options, Mycoplasma pneumoniae is the most likely causative agent, as it is specifically recognized as a cause of maculopapular rashes in febrile patients. 1

Critical Diagnostic Features Present

The constellation of findings in this patient points away from the other listed organisms:

• Positive Nikolsky sign is pathognomonic for conditions causing epidermal separation, specifically SJS/TEN, pemphigus vulgaris, and staphylococcal scalded skin syndrome (SSSS), but NOT for rickettsial, gonococcal, or paramyxovirus infections 2, 3

• Desquamation of skin and mucous membranes (tongue involvement) is characteristic of SJS/TEN and SSSS, which distinguishes these conditions from simple infectious exanthems 2

• The prodromal viral-like illness followed by progressive rash fits the typical presentation of drug-induced SJS/TEN or infection-associated mucocutaneous syndromes 2

Why Not the Other Options

Rickettsia rickettsii (Rocky Mountain Spotted Fever)

• RMSF presents with centrifugal spread starting at ankles/wrists progressing centrally, not centrifugal spreading from trunk 4, 5
• Nikolsky sign is NOT a feature of RMSF - the rash progresses from maculopapular to petechial but does not cause epidermal separation 1
• RMSF rash typically appears 2-4 days after fever onset and involves palms/soles by days 5-6, but desquamation and Nikolsky sign are absent 4

Neisseria gonorrhoeae

• Disseminated gonococcal infection causes sparse pustular or vesiculopustular lesions, not diffuse macular rash with desquamation 1
• No Nikolsky sign occurs with gonococcal infection 2
• Typically presents with tenosynovitis and migratory polyarthritis, not isolated skin findings 1

Paramyxoviridae (Measles virus)

• Measles causes a maculopapular rash that does NOT desquamate in the acute phase and never produces a positive Nikolsky sign 6
• The rash is characteristically cephalocaudal (head to toe), not centrifugal 6
• Koplik spots on buccal mucosa would be expected, not tongue desquamation 6

Mycoplasma pneumoniae as the Answer

• Mycoplasma pneumoniae is explicitly listed in CDC guidelines as causing maculopapular rashes in febrile patients 1
• M. pneumoniae is a well-recognized trigger of SJS/TEN and erythema multiforme major, which would explain the positive Nikolsky sign 1
• The prodromal respiratory/viral-like illness is consistent with atypical pneumonia caused by M. pneumoniae 1
• M. pneumoniae-induced mucocutaneous reactions characteristically involve mucous membranes (explaining tongue desquamation) and can progress to full-thickness epidermal necrosis 2

Critical Management Implications

• This patient requires immediate transfer to a burn unit or ICU given the positive Nikolsky sign indicating SJS/TEN 2
• Discontinue any potential culprit drugs immediately 2
• Initiate aggressive supportive care including IV fluid resuscitation, wound care with gentle handling, and infection prevention 2
• The extent of epidermal detachment has prognostic value and should be documented 2

Key Clinical Pitfall

The centrifugal spread might initially suggest RMSF, but the presence of Nikolsky sign and desquamation definitively excludes rickettsial disease and points to a mucocutaneous syndrome where M. pneumoniae is a recognized infectious trigger among the options provided 1, 2, 3.