No Established Association Between Melkersson-Rosenthal Syndrome and Interstitial Nephritis
There is no documented association between Melkersson-Rosenthal Syndrome (MRS) and interstitial nephritis in the medical literature. The available evidence on MRS does not identify renal involvement, including interstitial nephritis, as a feature or complication of this rare neuromucocutaneous disorder.
Understanding Melkersson-Rosenthal Syndrome
MRS is characterized by a classic triad of clinical features:
- Recurrent orofacial edema (most common initial finding, particularly affecting the lips) 1, 2
- Relapsing facial nerve palsy (indistinguishable from Bell's palsy) 2, 3
- Fissured tongue (lingua plicata) (present in approximately 34-47% of cases) 2, 4
The complete triad is rarely observed simultaneously, occurring in only 13% of biopsy-confirmed cases 4. Monosymptomatic and oligosymptomatic variants are far more common, making diagnosis challenging 2, 4.
Pathophysiology and Systemic Involvement
The histopathologic hallmark of MRS is noncaseating granulomatous inflammation, similar to sarcoidosis, though these granulomas are not invariably present 2, 4. The etiology remains unclear, with proposed mechanisms including:
- Genetic predisposition (family history noted in some cases) 3
- Immunologic dysregulation (elevated IgG levels reported in isolated cases) 3
- Infectious triggers (possible viral associations) 1, 3
Documented Systemic Associations
When reviewing large case series of MRS patients, the documented comorbidities include 4:
- Periodontal disease (14%)
- Allergic diseases (14%)
- Crohn's disease (8%)
- Migraine headaches (7%)
- Systemic lupus erythematosus (3%)
Notably absent from all published case series and reviews is any mention of renal disease, interstitial nephritis, or kidney involvement as a feature of MRS 1, 2, 3, 4, 5.
Complement Abnormalities: A Potential Confounding Factor
One case report documented low C3 and C4 levels in an MRS patient, but these were attributed to concurrent antiphospholipid antibodies rather than the MRS itself 1. Importantly, C1q and C1-inhibitor levels were normal in this patient, ruling out complement-mediated angioedema 1. A larger retrospective study found no patients with low C1q or C4 levels among those tested 4.
These complement findings do not suggest renal involvement, as interstitial nephritis typically does not present with isolated C3/C4 depression without other renal manifestations.
Clinical Pitfalls and Diagnostic Considerations
Common diagnostic challenges include:
- Misdiagnosis as angioedema: MRS can mimic hereditary or acquired angioedema, requiring careful differentiation 1
- Overlap with granulomatous diseases: The differential diagnosis includes sarcoidosis, Crohn's disease, and infectious granulomatous conditions 2
- Delayed diagnosis: Median time from symptom onset to diagnosis ranges from 1-35 years, with a median of 4 years 4
If a patient presents with both MRS and renal disease, these should be considered separate, unrelated conditions requiring independent evaluation and management. The renal disease would warrant standard nephrology workup including kidney biopsy to establish the specific diagnosis 6.
Treatment Implications
MRS treatment focuses on the granulomatous inflammation and includes 3, 4, 5:
- Systemic corticosteroids (first-line therapy with consistent response)
- Intralesional corticosteroids (triamcinolone acetonide)
- Antibiotics (doxycycline, metronidazole)
- Immunosuppressants in refractory cases (methotrexate, thalidomide)
None of these treatments are selected based on renal considerations, as kidney involvement is not a recognized feature of MRS 3, 4, 5.