What investigations are recommended for a patient with asymptomatic bilateral lower leg mottling suggestive of livedo reticularis, with stable heart failure with preserved ejection fraction (HFpEF), normal renal function, and normal electrolytes, while on dipagliflozin (SGLT2 inhibitor)?

Recommended Investigations for Asymptomatic Livedo Reticularis in a Stable HFpEF Patient on Dapagliflozin

In a patient with asymptomatic bilateral lower leg mottling (livedo reticularis), stable HFpEF, normal renal function, and normal electrolytes on dapagliflozin, minimal investigation is warranted since this is likely benign physiologic livedo reticularis that does not require treatment. 1, 2

Initial Clinical Assessment

The first step is to distinguish between benign livedo reticularis and pathologic livedo racemosa by examining the pattern and associated features:

• Livedo reticularis presents as a regular, symmetric, net-like pattern that blanches with warming and is typically benign 1, 2
• Livedo racemosa shows an irregular, broken, asymmetric pattern that persists with warming and suggests underlying pathology 1, 2

Specifically assess for these concerning features that would indicate pathologic livedo:

• Presence of skin nodules, ulceration, or necrosis 3
• Retiform purpura or non-blanching lesions 3
• Acute or fulminant onset rather than chronic/stable course 3
• Constitutional symptoms (fever, weight loss, malaise) 3
• New neurologic symptoms or stroke 1

Laboratory Investigations Based on Clinical Findings

If the pattern is regular, symmetric, and the patient remains asymptomatic with stable vital signs, no laboratory workup is necessary. 1, 2

However, if there are any concerning features listed above, obtain the following targeted investigations:

• Antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein I) if livedo racemosa pattern is present, as this is the most common pathologic association 1, 2
• Complete blood count with differential to assess for thrombocytopenia or polycythemia 3
• Inflammatory markers (ESR, CRP) if vasculitis is suspected 3
• Complement levels (C3, C4) and ANA if autoimmune disease is considered 3
• Cryoglobulins and hepatitis serologies if cryoglobulinemia is suspected 3

Skin Biopsy Considerations

Skin biopsy is generally not indicated for asymptomatic livedo reticularis with a benign appearance. 1, 2

Biopsy should only be performed if:

• The diagnosis remains uncertain after clinical assessment 4
• Pathologic livedo racemosa is suspected 4
• There are associated skin lesions (nodules, ulcers, purpura) requiring histologic diagnosis 4

If biopsy is performed, obtain multiple 4mm punch biopsies from both the central blanched areas and peripheral erythematous areas to increase diagnostic yield. 4

Relationship to Dapagliflozin Therapy

Dapagliflozin does not cause livedo reticularis and should not be discontinued based on this finding alone. 5, 6

The patient's stable clinical status with normal renal function and electrolytes on dapagliflozin indicates:

• The SGLT2 inhibitor is well-tolerated and providing cardiovascular benefit 5, 7
• The livedo is unrelated to the heart failure medication regimen 5
• Continue current HFpEF therapy without modification 7

Management Approach

For asymptomatic primary livedo reticularis, no treatment is required. 1, 2

Patient counseling should include:

• Reassurance that benign livedo reticularis is a common, harmless finding 1, 2
• Advice to avoid cold exposure and vasoconstricting substances (smoking, certain decongestants) 1
• Instructions to return if skin changes develop (ulceration, nodules, purpura) or systemic symptoms appear 3

Only if the patient develops symptoms (numbness, tingling, pain), consider:

• Calcium channel blockers for vasodilation 1
• However, use caution in HFpEF patients as blood pressure effects must be monitored 7

Common Pitfalls to Avoid

Do not order extensive autoimmune workup for symmetric, asymptomatic livedo reticularis in a clinically stable patient, as this leads to unnecessary testing and false-positive results. 1, 2

Do not discontinue beneficial HFpEF medications (dapagliflozin) based on unrelated benign skin findings. 5, 7

Do not perform skin biopsy routinely, as histopathology often shows non-specific findings and requires sampling both blanched and erythematous areas to be diagnostic. 4