Differential Diagnosis

The patient's initial presentation of erythematous plaques with pustules, followed by a skin biopsy suggesting acute generalized exanthematous pustulosis (AGEP), pustular psoriasis, and DRESS syndrome, and then evolving into erythema multiforme-like lesions with exfoliation, requires a broad differential diagnosis. Here's an organized approach:

• Single Most Likely Diagnosis
  • Generalized Exfoliative Dermatitis (GED): Given the progression to widespread exfoliation and the presence of erythema multiforme-like lesions without oral mucosa involvement, GED is a strong consideration. It can be triggered by drugs, and the initial treatment with topical mometasone cream and antihistamines might not have been sufficient to halt the progression, especially if the underlying cause was not fully addressed.
• Other Likely Diagnoses
  • DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms): Although the patient's vital signs are within normal limits, DRESS syndrome can present with a wide range of skin manifestations, including erythema multiforme-like lesions and exfoliation. The lack of oral mucosa involvement does not rule out DRESS, as mucosal involvement is not universal.
  • Pustular Psoriasis: The initial presentation could be consistent with pustular psoriasis, especially the generalized form. However, the evolution into erythema multiforme-like lesions is less typical, unless there was a superimposed drug reaction or another triggering factor.
  • Acute Generalized Exanthematous Pustulosis (AGEP): AGEP is characterized by numerous small pustules on an erythematous background, often triggered by drugs. While the initial presentation was suggestive of AGEP, the progression to erythema multiforme-like lesions and exfoliation might indicate a more complex or evolving condition.
• Do Not Miss Diagnoses
  • Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN): Although the patient does not have oral mucosa involvement and vital signs are normal, SJS/TEN can present with skin detachment and should always be considered in cases of severe skin reactions, especially if there's a suspicion of drug-induced causes. The absence of mucosal involvement does not entirely rule out SJS/TEN, as some cases may present atypically.
  • Severe Cutaneous Adverse Reaction (SCAR): This encompasses a range of severe reactions including DRESS, AGEP, SJS, and TEN. Given the patient's evolving clinical picture, considering SCAR is crucial, as it might require immediate withdrawal of potential offending drugs and supportive care.
• Rare Diagnoses
  • Autoimmune Subepidermal Blistering Diseases: Conditions like pemphigus or bullous pemphigoid could present with skin blistering and erosion but are less likely given the description of erythema multiforme-like lesions and the absence of clear blistering or mucosal involvement.
  • Paraneoplastic Pemphigus: A rare autoimmune disorder associated with underlying neoplasia, characterized by severe mucocutaneous blistering. Although mucosal involvement is typically a hallmark, its absence does not entirely rule out this diagnosis, especially in early or atypical cases.

Each of these diagnoses requires careful consideration of the patient's clinical presentation, history, and laboratory findings. Given the complexity and potential severity of these conditions, a thorough diagnostic workup, including further skin biopsies and potentially a drug challenge (if a specific drug is suspected), may be necessary to establish a definitive diagnosis.