What are the treatment considerations for a patient with seronegative rheumatoid arthritis, uncontrolled diabetes, and a genital rash while taking Plaquenil (hydroxychloroquine)?

Management of Seronegative Rheumatoid Arthritis with Uncontrolled Diabetes and Genital Rash on Hydroxychloroquine

Hydroxychloroquine should be discontinued immediately due to the genital rash, which may represent a serious adverse drug reaction, and alternative DMARD therapy should be initiated. 1

Assessment of the Current Situation

Evaluation of the Genital Rash

• Hydroxychloroquine can cause serious skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis 1
• A genital rash while on hydroxychloroquine requires immediate medical attention as it may represent one of these serious adverse reactions 1, 2
• The first documented case of DRESS syndrome caused by hydroxychloroquine was reported in a patient with seronegative arthritis 2

Consideration of Seronegative Status

• Seronegative RA may represent a diagnostic challenge, and the possibility of misdiagnosis or coexistent mimicking disease should be considered 3
• Ultrasonography may be considered to confirm the presence of inflammatory activity when there is doubt based on clinical assessment 3
• Seronegative status may influence treatment response; patients who are seronegative for rheumatoid factor may respond better to abatacept or tocilizumab rather than rituximab 3

Impact of Uncontrolled Diabetes

• Hydroxychloroquine can cause severe and potentially life-threatening hypoglycemia, which may complicate diabetes management 1
• Paradoxically, hydroxychloroquine has been shown to reduce the risk of diabetes in RA patients and has hypoglycemic effects 4
• Uncontrolled diabetes may be exacerbated by certain RA medications, particularly glucocorticoids 3

Treatment Recommendations

Immediate Management

1. Discontinue hydroxychloroquine due to the genital rash which may indicate a serious adverse reaction 1
2. Monitor closely for progression of skin reaction as retinal changes and visual disturbances may progress even after stopping therapy 1
3. Assess for systemic symptoms such as fever, lymphadenopathy, or organ involvement that might indicate DRESS syndrome 1, 2

Alternative DMARD Options

1. Consider triple DMARD therapy with methotrexate, sulfasalazine, and another agent (excluding hydroxychloroquine) 3

2. For patients with moderate to high disease activity, consider:

   • Methotrexate (15-25 mg/week as tolerated) as the cornerstone therapy 3
   • Addition of sulfasalazine as part of combination therapy 3
   • Consider biologic agents if disease activity remains high despite conventional DMARDs 3

3. For biologic therapy options in seronegative patients with inadequate response to conventional DMARDs:

   • TNF inhibitors (≤2 trials) 3
   • Abatacept (particularly in seronegative patients) 3
   • Tocilizumab (particularly in seronegative patients) 3

Managing Comorbid Diabetes

• Monitor blood glucose closely during DMARD transitions 1, 4
• Consider the impact of any new medications on glycemic control 3, 4
• Low-dose prednisone (≤10 mg/day) may be used cautiously if needed for disease control, with careful monitoring of glucose levels 3, 5
• Implement exercise interventions which can improve both RA symptoms and glycemic control 3

Follow-up Recommendations

• Reassess disease activity after 3-6 months of new treatment 3
• Monitor for development of any new adverse reactions to alternative therapies 3
• Consider ultrasonography to assess inflammatory activity if clinical assessment is challenging 3
• Implement consistent engagement in exercise which is strongly recommended for RA management 3

Potential Pitfalls and Considerations

• Avoid reintroduction of hydroxychloroquine due to risk of more severe reaction upon re-exposure 1
• Be cautious with glucocorticoid use due to potential worsening of diabetes; if used, limit to ≤10 mg/day 3, 5
• Remember that seronegative RA may sometimes represent misdiagnosis; reassess diagnosis if response to therapy is inadequate 3
• Consider that the effectiveness of hydroxychloroquine in RA is moderate (only 12% complete remission, 14% with ≥75% response in studies) 6, so alternative therapies may provide better disease control