Acquired cutis laxa associated with heavy chain deposition disease

Harrington, Cynthia R.; Beswick, Tracy C.; Susa, Joseph; Pandya, Amit G.

doi:10.1016/j.jaad.2008.05.007

Cited by 26 publications

(23 citation statements)

References 16 publications

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“…5 The predominant mesangial tropism of deposits in HCDD may account for the frequency of nodular glomerulosclerosis, observed in all of our patients and in most previously reported cases. [3][4][5][6][7][8][9][10][11][12][13][14][15][17][18][19][20][21][22] a-HCDD appears to differ from g-HCDD by the increased presence of glomerular extracapillary proliferation, reported in 2 of our 3 patients and in 6 of 6 previous cases in the literature. 3,5,19,20 Both displayed systemic monoclonal a-HC deposits, involving the lung and the skin and gastrointestinal tract, respectively.…”

Section: Discussionmentioning

confidence: 94%

“…In light and heavy chain deposition disease (LHCDD), deposits contain both Ig light and heavy chains, whereas they are restricted to a monoclonal Ig heavy chain (HC) without detectable LC in HCDD. [1][2][3] Since the first description of HCDD, 4 w50 cases have been reported, mostly characterized by g-HC, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and occasionally a-HC, 3,5,19,20 m-HC, 21 or d-HC deposits. 22 Nearly half of HCDD cases were in patients without a symptomatic B-cell disorder, a condition now referred to as monoclonal gammopathy of renal significance (MGRS).…”

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confidence: 99%

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Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management

Bridoux

Javaugue²,

Bender

et al. 2017

Kidney International

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Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by tissue deposition of a truncated monoclonal immunoglobulin heavy chain lacking the first constant domain. Pathophysiological mechanisms are unclear and management remains to be defined. Here we retrospectively studied 15 patients with biopsy-proven HCDD of whom 14 presented with stage 3 or higher chronic kidney disease, with nephrotic syndrome in 9. Renal lesions were characterized by nodular glomerulosclerosis, with linear peritubular and glomerular deposits of γ-heavy chain in 12 patients or α-heavy chain in 3 patients, without concurrent light chain staining. Only 2 patients had symptomatic myeloma. By serum protein electrophoresis/immunofixation, 13 patients had detectable monoclonal gammopathy. However, none of these techniques allowed detection of the nephrotoxic truncated heavy chain, which was achieved by immunoblot and/or bone marrow heavy chain sequencing in 14 of 15 patients. Serum-free kappa to lambda light chain ratio was abnormal in 11 of 11 patients so examined. Immunofluorescence studies of bone marrow plasma cells showed coexpression of the pathogenic heavy chain with light chain matching the abnormal serum-free light chain in all 3 tested patients. Heavy chain sequencing showed first constant domain deletion in 11 of 11 patients, with high isoelectric point values of the variable domain in 10 of 11 patients. All patients received chemotherapy, including bortezomib in 10 cases. Renal parameters improved in 11 patients who achieved a hematological response, as assessed by normalization of the free light chain ratio in 8 cases. Tissue deposition in HCDD relates to physicochemical peculiarities of both variable and constant heavy chain domains. Early diagnosis and treatment with bortezomib-based combinations appear important to preserve renal prognosis. Thus, monitoring of serum-free light chain is an indirect but useful method to evaluate the hematological response.

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management

Bridoux

Javaugue²,

Bender

et al. 2017

Kidney International

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“…3 While the heavy chain has also been detected in muscle and skin, it is unclear if such deposition typically results in disease. [4][5][6] Herein we describe the development of acquired cutis laxa in a patient with HCDD and hypocomplementemia. In addition, we report the distribution of heavy chain deposits on the surfaces of dermal elastic fibers with codeposits of complement components C1q and C3, suggesting that aggregated γ heavy chains can activate complement by the classic pathway, leading to a complement-mediated mechanism of elastic fiber degradation.…”

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confidence: 99%

Acquired Cutis Laxa Associated With Heavy Chain Deposition Disease Involving Dermal Elastic Fibers

et al. 2014

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The pathogenesis of cutis laxa in this condition is poorly understood. We hypothesize a mechanism of elastic tissue destruction by complement fixation with resultant activation of the complement cascade ultimately causing elastolysis. Based on our findings and those of other reports, we propose that skin heavy chain deposition can serve as a marker of plasma cell secretory activity in HCDD, although further studies are needed.

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“…Cutis laxa, a skin disorder related to elastic fiber degradation, has occasionally been reported in HCDD. 4 Elastic tissue damage results from HC deposition and subsequent complement activation. 5 CL belongs to the spectrum of diseases referred to as monoclonal gammopathy of cutaneous significance (MGCS).…”

Section: Discussionmentioning

confidence: 99%

Cutis laxa for diagnosis of γ1‐heavy‐chain deposition disease: Report of four cases

Battistella

Vignon

Baron

et al. 2018

The Journal of Dermatology

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Heavy-chain deposition disease (HCDD) is characterized by tissue deposits of a truncated monoclonal immunoglobulin heavy-chain (HC) on basement membranes. Diagnosis is usually made on kidney biopsy, showing nodular glomerulosclerosis with HC deposits which can be missed, resulting in delay in diagnosis. We report four γ1-HCDD patients presenting with cutis laxa, hypocomplementemia and hypoalbuminemia. In two patients, unsuspected HCDD was revealed by cutis laxa and diagnosis was made on skin biopsy. In all patients, serum albumin and complement represented surrogate markers for disease monitoring. In γ-HCDD, extrarenal manifestations such as cutis laxa may precede renal injury and are precious tools for an early diagnosis, which is crucial to avoid progression of irreversible renal and elastic tissue damage.

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Acquired cutis laxa associated with heavy chain deposition disease

Cited by 26 publications

References 16 publications

Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management

Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management

Acquired Cutis Laxa Associated With Heavy Chain Deposition Disease Involving Dermal Elastic Fibers

Cutis laxa for diagnosis of γ1‐heavy‐chain deposition disease: Report of four cases

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