Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome.

BACKGROUND: Crystal-storing histiocytosis (CSH) is a poorly described complication of monoclonal gammopathy featuring histiocyte lysosomal storage of kappa light chain (kappa LC) crystals. Although CSH is usually associated with systemic manifestations, renal involvement is uncommon. METHODS: To investigate the molecular mechanisms implicated in kappa LC crystallization, we performed immunopathological and molecular studies in three patients with CSH and renal Fanconi syndrome (CSH/FS). The V kappa sequences were determined, and resulting molecular models were compared with previously reported myeloma-associated FS kappa LC sequences. RESULTS: All patients presented with chronic tubulo-interstitial nephritis and renal FS with accumulation of monoclonal kappa LC crystals within proximal tubular cells. They showed peri-renal and interstitial infiltration by histiocytes containing eosinophilic crystalline inclusions (pseudo-pseudo-Gaucher cells). LC sequences were determined and assigned to their germline counterparts, in strong homology with previously reported myeloma-associated FS sequences. Comparison of CSH/FS V kappa domain 3D structures with the germline-encoded structures and those from patients with myeloma-associated FS underlined distinct hydrophobic residues exposed to the solvent in two patients, likely favouring the formation of a variant form of crystals that may further resist degradation after phagocytosis. CONCLUSION: Although CSH/FS and myeloma-associated FS are closely related disorders, peculiar mutations in the V domains of CSH/FS monoclonal kappa LCs, different from those in myeloma-associated FS, may account for crystal morphology, predominant accumulation within histiocytes and multiple organ involvement in CSH.

[Wissler-Fanconi syndrome and Still's disease in adults. Nosological and etiological problems and borderline forms. Apropos of 7 cases]. / Syndrome de Wissler-Fanconi et maladie de Still chez l'adulte. Problèmes nosologiques, étiologiques et formes frontières. A propos de sept observations.

In both Still disease and Wissler-Fanconi syndrome, onset may occur in adulthood and the clinical picture includes acute, often migratory, polyarthritis, polymorphic exanthema and a major inflammatory syndrome with fever (often intermittent) and high polymorphonuclear leukocyte counts. The grounds for this double designation are not clearly stated in the medical literature: does it refer to two separate entities or not? Some authors plainly stand for a unitary opinion. We report on seven cases in adults, five of which recovered without sequellae, while two developed respectively into rheumatoid arthritis and seronegative polyarthritis. We therefore propound a dualistic concept although, in the present state of our knowledge, there is no means of predicting at onset whether the disease will resolve or progress towards polyarthritis. We suggest that the term Still disease be used only when chronic and/or destructive arthritis develops. Among the forms which are neither chronic nor destructive, there seems to be a number of cases in allergic patients with poor tolerance of chrysotherapy. Some of these patients could recover after the cure of an often latent focal infection, usually of the upper respiratory tract, ear or oral cavity, resistant to antibiotics. In the other cases, corticosteroid therapy is usually very effective in arresting an exacerbation of the disease.

The clinical spectrum of Fanconi's syndrome.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California Medical Center, San Francisco. Taken from transcriptions, they are prepared by Drs. Martin J. Cline and Hibbard E. Williams, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine.