Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease
in patients due to calcification of cutaneous blood vessels. It is commonly
associated with renal failure and dialysis patients. It is a devastating disease
with a high rate of mortality and morbidity.
| DISEASE ASSOCIATIONS |
CHARACTERIZATION |
| AIDS |
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Widespread cutaneous and systemic calcification (calciphylaxis)
in patients with the acquired immunodeficiency syndrome and renal disease.
Cockerell CJ, Dolan ET.
University of Texas Southwestern Medical Center, Dallas.
|
J Am Acad Dermatol 1992 Apr;26(4):559-62 Abstract quote
ACKGROUND: Calciphylaxis is a form of widespread calcification that
may occur in patients with renal disease and hyperparathyroidism. The
skin is often affected secondary to vascular compromise and ischemia.
Patients infected with the human immunodeficiency virus (HIV) are predisposed
to renal failure and thus may develop this serious complication.
OBJECTIVE: The purpose of this article is to describe two cases of
fatal calciphylaxis in patients with the acquired immunodeficiency syndrome
and renal disease.
METHODS: Two patients were examined clinically and through the performance
of serologic studies and skin biopsies.
RESULTS: Both patients had a widespread livedo reticularis-like eruption,
which rapidly progressed to cutaneous gangrene. Patient 1 had elevated
serum calcium and phosphorus levels whereas patient 2 had normal values
but had markedly elevated serum parathyroid hormone levels. Biopsy specimens
in both cases showed vascular thrombosis and soft tissue calcification.
CONCLUSION: Widespread calcification may develop in patients with HIV
infection and renal failure and, in some cases, calcium and phosphorus
levels may be normal.
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| CHRONIC RENAL FAILURE |
|
|
Wet gangrene in hemodialysis patients with calciphylaxisis is associated
with a poor prognosis.
Davis CA, James Valentine R.
Division of Vascular Surgery, Department of Surgery, The University
of Texas Southwestern Medical Center, 75235-9031, Dallas, TX, USA
|
Cardiovasc Surg 2001 Dec;9(6):565-70 Abstract quote
Calciphylaxis is a rare syndrome characterized by progressive vascular
calcification and ischemic tissue loss in patients with chronic renal
failure. We report our five-year experience with five patients who developed
foot gangrene due to calciphylaxis. All five patients had characteristic
clinical, laboratory, and radiologic findings of the disorder, but no
diagnostic variable was uniformly present. All five had progressed to
advanced gangrene at the time of surgical consultation. Despite aggressive
local attempts to control infection, all five patients died of septic
complications. Parathyroidectomy was performed in three patients but
did not alter the course in any case. This small experience suggests
that the outcome of foot gangrene associated with calciphylaxis is predicated
on the degree of tissue loss. Aggressive local wound care does not appear
to be adequate to control infection in patients who have already developed
gangrene.
Although parathyroidectomy may have important long-term advantages
in patients with calciphylaxis, it does not appear to affect outcome
in these advanced cases.
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Calciphylaxis associated with cholangiocarcinoma treated with low-molecular-weight
heparin and vitamin K.
Riegert-Johnson DL, Kaur JS, Pfeifer EA.
Department of Internal Medicine, Mayo Clinic, Rochester, Minn 55905,
USA.
|
Mayo Clin Proc 2001 Jul;76(7):749-52 Abstract quote
Calciphylaxis is a rare disorder of small-vessel calcification and
cutaneous infarction associated with chronic renal failure. Rare cases
of calciphylaxis not associated with chronic renal failure have been
reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis.
To our knowledge, we report the first case of calciphylaxis without
chronic renal failure associated with cholangiocarcinoma and the first
attempt to treat calciphylaxis with vitamin K.
A 56-year-old woman presented with necrotic leg ulceration. She was
treated initially with low-molecular-weight heparin, with no effect.
A coagulation work-up showed vitamin K deficiency. During vitamin K
therapy, the patient had fulminant progression of the calciphylaxis.
She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis
and protein C deficiency have been implicated in the pathophysiology
of calciphylaxis.
Functional protein C deficiency may be one of several factors contributing
to the development of calciphylaxis. Vitamin K therapy was ineffective
in our patient and may have been detrimental.
|
|
Fulminant and relentless cutaneous necrosis with excruciating pain
caused by calciphylaxis developing in a patient undergoing peritoneal
dialysis.
Sato N, Teramura T, Ishiyama T, Tagami H.
Department of Dermatology, Akita Kumiai General Hospital, Japan.
|
J Dermatol 2001 Jan;28(1):27-31 Abstract quote
A 50-year-old Japanese female with chronic renal failure who had been
on continuous ambulatory peritoneal dialysis developed fulminant systemic
cutaneous necrosis that began as painful livedo reticularis-like skin
lesions on her thighs. Because of disseminated vascular calcification
within the muscular layer of her lower limbs, we eventually diagnosed
her with calciphylaxis. The skin necrosis progressed rapidly, and she
died of sepsis and pneumonia on the 53rd hospital day. In addition to
her long-lasting severe hyperparathyroidism and extremely elevated serum
phosphorus and calcium levels, mechanical, frictional stimulation inflicted
on the local skin and administration of corticosteroids were suspected
to have precipitated the calciphylaxis.
Our lack of awareness of this disease in its early stages resulted
in our missing the chance to do a parathyroidectomy that might have
changed the course. It is important to know the clinical features of
this rare disease in order to make a diagnosis as early as possible.
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| HYPERPARATHYROIDISM |
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|
An unusual presentation of calciphylaxis due to primary hyperparathyroidism.
Mirza I, Chaubay D, Gunderia H, Shih W, El-Fanek H.
Departments of Pathology (Drs Mirza, Gunderia, and El-Fanek) and Internal Medicine (Drs Chaubay and Shih), Danbury Hospital, Danbury, Conn. |
Arch Pathol Lab Med 2001 Oct;125(10):1351-3 Abstract quote
We present the case of a 69-year-old woman with calciphylaxis due to primary hyperparathyroidism. A 0.5-g parathyroid adenoma was surgically removed, which resulted in complete recovery of the patient.
Review of the literature revealed 7 other cases of calciphylaxis due to primary hyperparathyroidism and showed that prompt surgical removal of the autonomous parathyroid gland lesion results in clinical recovery of calciphylactic skin lesions. |
| NEPHROGENIC FIBROSING DERMOPATHY |
|
Calciphylaxis and metastatic calcification associated with nephrogenic fibrosing dermopathy
Lisa C. Edsall, Joseph C. English III and James W. Patterson
|
Journal of Cutaneous Pathology
Volume 31 Issue 3 Page 247 - March 2004 Abstract quote
Background: Calciphylaxis and metastatic calcification are known complications of chronic renal failure. Recently, a sclerosing condition of the skin termed nephrogenic fibrosing dermopathy (NFD) has been described in patients with renal disease, many of whom have undergone hemodialysis and/or renal transplantation. To our knowledge, the simultaneous occurrence of both conditions in the same patient, in the same lesion, has not been previously reported.
Case report: We report the clinical, microscopic, and immunohistochemical features of two patients with chronic renal failure whose lesional skin biopsies showed both subcutaneous calcification and NFD. We consider the possible mechanisms that might explain the coexistence of these two disorders.
Results: Both patients presented with erythematous, indurated skin over the lower extremities. Purpuric, reticulated patches, necrosis, or ulceration were not observed. Microscopic examination showed the characteristic changes of NFD involving dermis and subcutaneous septa. In addition, biopsies of both individuals showed subcutaneous calcification, one in a diffuse distribution and the other involving the walls of subcutaneous vessels, as seen in calciphylaxis. Calcification was not suspected clinically in either case.
Conclusions: Metastatic calcification or calciphylaxis and NFD can occur simultaneously in patients with chronic renal failure and may be found together in the same lesion. Because subcutaneous calcification may not be suspected clinically in these cases, and in view of the adverse outcomes frequently associated with calciphylaxis, we recommend deep incisional biopsy of patients presenting with the clinical features of NFD. Both the fibrosis and the calcification of chronic renal failure may be related to the activity of transforming growth factor-/Smad signaling cascades
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| PATHOGENESIS |
CHARACTERIZATION |
| GENERAL |
|
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Three-dimensional analysis of a calciphylaxis plaque: clues to pathogenesis.
Au S, Crawford RI.
Division of Dermatology, Department of Pathology, University of
British Columbia, Vancouver, BC, Canada V6Z 1Y6
|
J Am Acad Dermatol 2002 Jul;47(1):53-7 Abstract quote
BACKGROUND: Calciphylaxis is a rare, life-threatening disorder associated
with chronic renal failure, presenting with ulcerating plaques leading
to death by sepsis in 60% of patients. Calcification of subcutaneous
arterioles, thromboses, and extravascular calcification have been demonstrated
in incisional biopsy specimens. However, the sequence of these pathologic
events is unknown.
OBJECTIVE: We examined a calciphylaxis plaque to document the wave
of pathologic change from its center to its periphery.
METHODS: A calciphylaxis plaque was excised postmortem from a female
patient. It was examined histologically along 12 radii from the center
of the lesion to its periphery.
RESULTS: Calcification of small subcutaneous vessels was present in
all histologically abnormal sections and extended further peripherally
than extravascular calcification by up to 3.0 cm and further than subcutaneous
thrombosis by up to 1.5 cm.
CONCLUSION: Vascular mural calcification is an early and essential
process in the development of a calciphylaxis plaque.
|
| CALCIUM-PHOSPHOROUS PRODUCT |
|
|
Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus
product in dialysis patients.
Levin NW, Hoenich NA.
Renal Research Institute, New York, New York, USA.
|
Curr Opin Nephrol Hypertens 2001 Sep;10(5):563-8 Abstract quote
Control of serum phosphorus levels is a central goal in the management
of patients with chronic renal failure. Inadequate control of serum
phosphorus leads to elevated levels of the calcium-phosphorus product.
This plays a pivotal role in vascular calcification, cardiovascular
disease, calciphylaxis, and death.
Elevated phosphorus and elevated levels of the calcium-phosphorus product
are both significant predictors of cardiovascular mortality, at phosphorus
and calcium-phosphorus product levels that were considered safe until
recently.
A lowering of levels such that phosphorus is maintained between 2.2
and 5.5 mg/dl, calcium-phosphorus product is below 55 mg2/dl2, and serum
calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of
therapeutic management strategies.
|
|
Calciphylaxis is associated with hyperphosphatemia and increased
osteopontin expression by vascular smooth muscle cells.
Ahmed S, O'Neill KD, Hood AF, Evan AP, Moe SM.
Departments of Medicine, Pathology, and Anatomy, Indiana University
School of Medicine, Indianapolis 46202, USA.
|
Am J Kidney Dis 2001 Jun;37(6):1267-76 Abstract quote
Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease
in dialysis patients due to calcification of cutaneous blood vessels.
The pathogenesis has been attributed to elevated parathyroid hormone
(PTH). However, recent studies evaluating vascular calcification in
nondialysis patients have found that the smooth muscle cells play an
active role, including production of the bone matrix protein osteopontin.
To examine the involvement of various clinical parameters and smooth
muscle cells of CUA, we performed a case-control analysis comparing
10 CUA patients with our current dialysis patients.
Available histologic sections were immunostained for osteopontin, markers
of smooth muscle cells, endothelial cells, and macrophages. Compared
with our current dialysis population, patients with CUA were more likely
to be obese, white, and female (P < 0.02). Comparison of laboratory
values found CUA patients with lower serum albumin, greater serum phosphorus,
and greater calcium X phosphorus product (P < 0.01). In contrast, there
was no difference in the concentration of PTH or calcium between the
2 groups. Immunostaining of calcified blood vessels showed that all
calcified vessels stained positive for osteopontin, whereas all the
noncalcifed vessels showed no osteopontin localization. Staining for
smooth muscle alpha-actin decreased in the medial layer with calcification,
with cells appearing to be sloughed off, leading to near occlusion of
the vessel lumen.
Our case-control study demonstrates that hyperphosphatemia and an elevated
calcium X phosphorus product is associated with CUA. Histologic examination
suggests that the calcification is associated with increased expression
of osteopontin by smooth muscle cells.
|
|
The development of the pathophysiological concept of calciphylaxis
in experiment and clinic.
Vasků V V, Vasků J.
VACORD Bioengineering Research Company, 614 00 BRNO-Husovice, 53,
Cacovicka, Czech Republic
|
Pathophysiology 2001 Mar;7(4):231-244 Abstract quote
An attempt to clarify some pathophysiological aspects of calciphylaxis
from both experimental and clinical points of view is presented. Until
now, we cannot explain precisely various forms of calcification, affecting
either soft tissues or biomaterial as well, only on the basis of metastatic
or dystrophic calcification including the pure topical, local aspects.
Therefore, the biological phenomenon of calciphylaxis can be useful
in searching the ways for the inhibition of soft tissues and biomaterial
calcification.
The experiments with experimental progeria have also made it possible
to study the so-called reversed calciphylaxis. The systemic reversed
calciphylaxis, or 'anacalciphylaxis' was shown in the authors experiments
with the total artificial heart as a very effective factor in the inhibition
of mineralization of the TAH driving diaphragms. The discovery of the
ubiquitous organ regulator of calcification, osteopontin, can greatly
contribute to further elucidation of the calciphylactic mechanisms in
general, and also to the prevention of calcifying lesions. It is pointed
to some clinical states, predominantly the end-stage renal disease with
hemodialysation where many authors pay attention to calciphylaxis as
a clinical entity in a series of such cases.
Calciphylaxis has been described in dermatology, nephrology and other
clinical disciplines. In the area of attempts to prevent the ectopic
organ calcification and also mineralization of biomaterials, a vast
field of stimulation of endogenic inhibitors of calcification remains
open.
|
GROSS APPEARANCE/
CLINICAL VARIANTS |
CHARACTERIZATION |
| GENERAL |
|
| VARIANTS |
|
| PROXIMAL |
|
|
A case control study of proximal calciphylaxis.
Bleyer AJ, Choi M, Igwemezie B, de la Torre E, White WL.
Department of Pathology, Bowman Gray School of Medicine, Winston-Salem,
NC 27157, USA.
|
Am J Kidney Dis 1998 Sep;32(3):376-83 Abstract quote
The purpose of this investigation was to describe the clinical presentation
of nine patients with calciphylaxis involving the proximal lower extremities
or trunk and to compare the clinical characteristics of these patients
with those of 347 hemodialysis patients from the same geographic area.
Patients were identified primarily through a computer search of pathology
records, identifying patients with the term "calciphylaxis" in the biopsy
report. All patients had pathologic specimens consistent with calciphylaxis.
All the calciphylaxis patients were white and were markedly obese. While
two patients had markedly elevated parathyroid hormone levels, most
patients did not show severe derangements of calcium phosphate metabolism
compared with other dialysis patients. A logistic regression model identified
body mass index and low serum albumin 3 months before diagnosis as being
highly associated with a diagnosis of calciphylaxis.
Diabetes mellitus and parameters of calcium-phosphate metabolism were
not significantly associated with proximal calciphylaxis. These findings
suggest that white race, morbid obesity, and poor nutritional status
are associated with proximal calciphylaxis in dialysis patients.
|
| PENIS |
|
|
Penile calciphylaxis: rare necrotic lesions in chronic renal failure
patients.
Jhaveri FM, Woosley JT, Fried FA.
Department of Pathology, University of North Carolina School of
Medicine, Chapel Hill 27599-7235, USA.
|
J Urol 1998 Sep;160(3 Pt 1):764-7 Abstract quote
PURPOSE: Calciphylaxis is a rare devastating condition of cutaneous
necrosis resulting from calcification of small blood vessels in patients
with end stage renal failure and secondary hyperparathyroidism. We describe
5 patients with penile calciphylaxis at a single institution.
MATERIALS AND METHODS: From 1992 to 1996, 5 patients had penile calciphylaxis.
The charts of these patients were reviewed to determine the nature of
the lesions, association with hyperparathyroidism and treatment outcomes.
RESULTS: All 5 patients had chronic renal failure, secondary hyperparathyroidism
and painful necrotic lesions at multiple sites. Radiographs showed stippled
calcification of small vessels, which was confirmed histologically.
Three patients had undergone parathyroidectomy with a significant decrease
in mean calcium x phosphorus ion products from 86.01 to 45.37 mg.2/dl.2
(p < 0.001), and in 1 calciphylaxis resolved postoperatively. The penile
lesions were treated with debridement and aggressive wound care.
CONCLUSIONS: The increase in the number of patients with chronic renal
failure on dialysis may make penile calciphylaxis more prevalent in
the future. Lowering of serum calcium and phosphorus levels, and debridement
of these necrotic lesions help to diminish this aggressively destructive
process.
|
|
Calciphylaxis, a poorly understood clinical syndrome: three case
reports and a review of the literature.
Howe SC, Murray JD, Reeves RT, Hemp JR, Carlisle JH.
Division of Vascular Surgery, Naval Medical Center San Diego, 92134-5000,
USA.
|
Ann Vasc Surg 2001 Jul;15(4):470-3 Abstract quote
Systemic calcification syndromes are a recognized complication occurring
in some patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism.
These patients develop severe livedo reticularis and subcutaneous tissue
lesions progressing to frank necrosis and ultimately large areas of
eschar. Clinically this syndrome is known as calciphylaxis; these lesions
are usually resistant to aggressive debridement, systemic antibiotics,
and revascularization procedures.
We report three patients with somewhat different clinical presentations
but all sharing a common link of exquisitely painful leg ulcers initially
being treated as ischemic lesions or venous stasis-type ulcerations.
These three patients were diagnosed with calciphylaxis on the basis
of clinical, biochemical, and histopathological criteria. Two patients
underwent parathyroidectomy late in the progression of their disease,
with some resolution of their ulcerative lesions.
|
| PULMONARY FAILURE |
|
|
Acute respiratory failure due to "pulmonary calciphylaxis" in a
maintenance haemodialysis patient.
Matsuo T, Tsukamoto Y, Tamura M, Hanaoka M, Nagaoka T, Kobayashi
Y, Higashihara M, Yokoyama H, Saegusa N.
Fourth Department of Internal Medicine, Kitasato University, Kanagawa,
Japan.
|
Nephron 2001 Jan;87(1):75-9 Abstract quote
Calciphylaxis is a rapidly developing, fatal process of vascular calcium
deposition with prominent cutaneous manifestation. We treated a long-term
haemodialysis patient who developed an analogous disorder limited to
the lungs.
A 57-year-old man was admitted for initiation of peritoneal dialysis
because limited cardiac reserve precluded further haemodialysis. He
was treated successfully for pneumonia until hypoxia and progressive
hypercalcaemia developed. (99m)Tc-methylene disphosphonate scintigraphy
showed diffusely increased pulmonary uptake. Death supervened despite
aggressive and successful treatment of hypercalcaemia.
Autopsy studies included immunohistochemistry and morphometric studies
of bone. Alveolar capillary walls showed diffuse calcium deposition.
Both gross and microscopical findings differed from those of typical
metastatic calcification in dialysis patients. Immunoreactivity for
parathyroid hormone-related protein was present in the lesions. Bone
histomorphometry indicated mild osteitis fibrosa. Pneumonia is believed
to have caused local synthesis of parathyroid hormone-related protein
that, along with high calcium x phosphorus product, contributed to calcium
deposition.
By analogy with the cutaneous process we termed the deposition "pulmonary
calciphylaxis".
|
| RENAL FAILURE ABSENCE |
|
|
Calciphylaxis in a patient with Crohn's disease in the absence of end-stage renal disease.
Barri YM, Graves GS, Knochel JP.
Department of Medicine, Presbyterian Hospital of Dallas, TX 75231, USA. |
Am J Kidney Dis 1997 May;29(5):773-6 Abstract quote
Calciphylaxis is a rare and life-threatening condition of progressive cutaneous necrosis secondary to small and medium-sized vessel calcification previously described in patients with end-stage renal disease and hyperparathyroidism. Early diagnosis may be important in improving the poor outcome in these patients since early intervention may forestall the development of life-threatening complications.
We describe a patient with Crohn's disease complicated by short-bowel syndrome and modest renal insufficiency (not requiring renal replacement therapy) who developed calciphylaxis. It appears that longstanding Crohn's disease and the short-bowel syndrome accelerated the development of calciphylaxis as the chronic renal disease was not end stage. Considering the possibility of calciphylaxis in this setting may avoid delaying the diagnosis and its consequences. |
|
Calciphylaxis in the absence of renal failure.
Pollock B, Cunliffe WJ, Merchant WJ.
Departments of Dermatology and Histopathology, Leeds General Infirmary, UK. |
Clin Exp Dermatol 2000 Jul;25(5):389-92 Abstract quote
We report a patient with severe bilateral leg ulceration that was resistant to treatment. A biopsy confirmed the cause as calciphylaxis. Calciphylaxis refers to a syndrome of calcium deposition in the small and intermediate dermal vasculature which can lead to epidermal ischaemia, ulceration and necrosis. Most cases occur in those with chronic renal failure and secondary hyperparathyroidism. We describe the rare presentation of calciphylaxis in a patient with normal renal function and primary hyperparathyroidism who had many classical features. Unfortunately she developed gangrene, sepsis and died. |
| HISTOLOGICAL TYPES |
CHARACTERIZATION |
|
Pathogenesis of calciphylaxis: study of three cases with literature
review.
Fischer AH, Morris DJ.
Department of Pathology, Carney Hospital, Boston, MA, USA.
|
Hum Pathol 1995 Oct;26(10):1055-64 Abstract quote
Calciphylaxis is characterized by ischemic necrosis, primarily of skin.
The early phase of the ischemia has not been studied, and the pathogenesis
is uncertain.
In this study of early calciphylaxis, the vessels responsible for the
ischemia seem to be within the material available for microscopic review,
and the various stenosing vascular lesions are quantified.
A distinctive and previously described small vessel calcification with
superimposed endovascular fibrosis is most common, and is much more
frequent than two other lesions proposed to cause the ischemia (thrombosis
and global calcific obliteration). The calcified stenotic vessels average
100 microns in diameter. Calcification precedes the endovascular fibrosis.
Vessels with early endovascular fibroblastic activation are found statistically
to be strongly associated with the presence of a giant cell reaction.
This endovascular giant cell reaction has not been previously described
in calciphylaxis. Two additional cases show similar findings.
The histology resembles the reaction to calcium in a variety of other
extraosseous calcification syndromes, for example, pseudogout, as if
calciphylaxis were an endovascular form of calcium crystal-induced inflammatory
disease. The literature is reviewed, and the clinicopathologic, radiographic,
and therapeutic implications are discussed.
|
|
Calciphylaxis with histologic changes of pseudoxanthoma elasticum.
Nikko AP, Dunningan M, Cockerell CJ
Division of Dermatopathology, University of Texas Southwestern Medical
Center, Dallas, USA.
|
Am J Dermatopathol 1996 Aug;18(4):396-9 Abstract quote
Calciphylaxis is a rare condition of widespread calcification of tissues
and blood vessels with accompanying vascular thrombosis and ischemic
necrosis. Most cases develop in association with hyperparathyroidism
in patients with chronic renal failure.
Pseudoxanthoma elasticum (PXE) is a hereditary condition of abnormal
elastic tissue structure that leads to widespread abnormalities of the
skin, retina, and visceral organs. Histologic changes of PXE have been
observed as coincidental findings in several conditions such as following
trauma to the skin manifest as isolated plaques often in scars.
We observed histologic findings of PXE in a patient with chronic renal
failure who developed fatal calciphylaxis. Complete evaluation failed
to reveal evidence of systemic findings of PXE. Histologic changes of
PXE may be seen in patients with calciphylaxis as a coincidental finding.
Rapidly developing soft tissue calcification may lead to the expression
of the characteristic histopathologic findings of PXE without evidence
of classic clinical manifestations of PXE.
Calciphylaxis should be added to the list of disorders that may lead
to microscopic PXE-like changes.
|
|
Cutaneous calciphylaxis. An underrecognized clinicopathologic entity.
Essary LR, Wick MR.
Department of Pathology, University of Alabama at Birmingham Medical
Center, USA.
|
Am J Clin Pathol 2000 Feb;113(2):280-7 Abstract quote
Calciphylaxis (CPX), an uncommon syndrome characterized, in part, by
progressive cutaneous vascular calcification, is seen principally in
the setting of renal failure-associated hyperparathyroidism and is difficult
to distinguish histologically from other microvasculopathies.
We assessed histologic specimens from 13 cases of clinicopathologically
classic CPX of the skin and reviewed documented histologic findings
in the literature.
Our series included 7 "early" and 6 "late" lesions (absence or presence
of tissue necrosis, respectively). Histologically, early lesions were
subtle and almost inapparent microscopically. Late lesions were easier
to recognize because of obvious epidermal ulceration, dermal necrosis,
and easily seen mural vascular calcification.
The most common finding in both groups was acute and chronic calcifying
septal panniculitis. Endovascular fibroblastic proliferation was more
common in advanced lesions. Necrosis of dermal collagen was identified
in only a few early lesions. Frank luminal vascular thrombosis was infrequent
in both groups. The cited histologic findings largely were mirrored
by those in the literature.
Although they are relatively nonspecific when considered in isolation,
the cited histopathologic features of cutaneous CPX allow for the diagnosis
of this potentially lethal disorder when they are seen in combination
with one another, particularly if detailed clinical data also are available.
|
| VARIANTS |
|
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSTIC FACTORS |
|
| GENERAL |
|
|
Risk factors and mortality associated with calciphylaxis in end-stage
renal disease.
Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL,
Stehman-Breen CO.
University of Washington, Division of Nephrology, Seattle, Washington,
USA. |
Kidney Int 2001 Jul;60(1):324-32 Abstract quote
BACKGROUND: We conducted a case control study to determine risk factors
and mortality associated with calciphylaxis in end-stage renal disease.
METHODS: Cases of calciphylaxis diagnosed between December 1989 and
January 2000 were identified. Three controls were identified for each
hemodialysis patient, with calciphylaxis matched to the date of initiation
of hemodialysis. Laboratory data and medication doses were recorded
during the 12 months prior to the date of diagnosis and at the time
of diagnosis of calciphylaxis. Conditional logistic regression was used
to identify risk factors for calciphylaxis. Cox proportional hazards
models were used to estimate the risk of death associated with calciphylaxis.
RESULTS: Nineteen cases and 54 controls were identified. Eighteen
patients were hemodialysis patients, and one had a functioning renal
allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women
were at a sixfold higher risk of developing calciphylaxis (OR = 6.04,
95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis
associated with each 0.1 g/dL increase in the mean serum albumin during
the year prior to diagnosis and at the time of diagnosis of calciphylaxis
(OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI,
0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase
in the risk of calciphylaxis associated with each mg/dL increase in
the mean serum phosphate during the year prior to diagnosis (95% CI,
0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis,
for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis
increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body
mass index, diabetes, blood pressure, aluminum, and higher dosage of
erythropoietin and iron dextran were not independent predictors of calciphylaxis.
Calciphylaxis independently increased the risk of death by eightfold
(OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001).
CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase,
and low serum albumin are risk factors for calciphylaxis. Calciphylaxis
is associated with a very high mortality. |
| GANGRENE |
|
|
Wet gangrene in hemodialysis patients with calciphylaxisis is associated
with a poor prognosis.
Davis CA, Valentine RJ.
Division of Vascular Surgery, Department of Surgery, The University
of Texas Southwestern Medical Center, Dallas, TX 75235-9031, USA. |
Cardiovasc Surg 2001 Dec;9(6):565-70 Abstract quote
Calciphylaxis is a rare syndrome characterized by progressive vascular
calcification and ischemic tissue loss in patients with chronic renal
failure.
We report our five-year experience with five patients who developed
foot gangrene due to calciphylaxis. All five patients had characteristic
clinical, laboratory, and radiologic findings of the disorder, but no
diagnostic variable was uniformly present. All five had progressed to
advanced gangrene at the time of surgical consultation. Despite aggressive
local attempts to control infection, all five patients died of septic
complications. Parathyroidectomy was performed in three patients but
did not alter the course in any case. This small experience suggests
that the outcome of foot gangrene associated with calciphylaxis is predicated
on the degree of tissue loss. Aggressive local wound care does not appear
to be adequate to control infection in patients who have already developed
gangrene.
Although parathyroidectomy may have important long-term advantages
in patients with calciphylaxis, it does not appear to affect outcome
in these advanced cases. |
| SURVIVAL |
|
|
Calciphylaxis: a poor prognostic indicator for limb salvage.
Mureebe L, Moy M, Balfour E, Blume P, Gahtan V.
Section of Vascular Surgery, the Department of Orthopedics, Yale
University School of Medicine, New Haven, Conn, USA. |
J Vasc Surg 2001 Jun;33(6):1275-9 Abstract quote
INTRODUCTION: Calciphylaxis (calcific uremic arteriolopathy) is a rare
complication of end-stage renal disease in patients with secondary hyperparathyroidism.
Subcutaneous skin nodules and extensive tissue necrosis with vascular
calcification characterize this process.Design and Setting: The design
of the study included case series and literature review. The study was
set in a tertiary care hospital.
PATIENTS: Four patients presented over an 8-month period with extensive
tissue loss and the subsequent diagnosis of calciphylaxis. Two of these
patients were revascularized. One underwent primary amputation, and
the final patient died before revascularization. The mortality rate
for this group was 75%. All patients had significant vascular complications
outside the area of initial presentation.
CONCLUSIONS: These individuals represent a subset of patients who may
not benefit from revascularization or may require extensive regulation
of divalent metabolism before consideration for revascularization. |
| TREATMENT |
|
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Intensive tandem cryofiltration apheresis and hemodialysis to treat
a patient with severe calciphylaxis, cryoglobulinemia, and end-stage
renal disease.
Siami GA, Siami FS.
Vanderbilt University Medical Center, Department of Medicine, Nashville,
Tennessee, USA. |
ASAIO J 1999 May-Jun;45(3):229-33 Abstract quote
This is the first report on tandem cryofiltration apheresis (CFA) and
hemodialysis (HD).
A 44 year old white man with Type II mixed cryoglobulinemia, hepatitis
C virus (HCV), severe skin lesions, and end-stage renal disease (ESRD)
on maintenance hemodialysis was air-transferred for CFA, which is only
available at our medical center. The patient failed to respond to high
dose steroids, immunosuppression, intravenous immunoglobulin (IVIG),
and plasma exchange for the treatment of his cryoglobulinemia, and he
failed alpha-interferon therapy for his HCV. On arrival, he was also
found to have severe calciphylaxis secondary to ESRD with generalized,
painful skin ulceration, necrosis, and penile gangrene. To treat both
conditions, intensive, tandem CFA/HD was initiated. He received extensive
wound care and surgical debridement. To prevent pressure ulcers and
worsening of skin lesions, he was placed on the FluidAir (Kinetic Concepts
Inc., San Antonio, TX) controlled air bed. The patient received 18 tandem
CFA/HD treatments, and four extra HD treatments in one month. Sodium
citrate was used as an anticoagulant for the CFA procedure. His plasma
cryoglobulin (CG) level dropped from 6,157 to 420 microg/ml, and his
calciphylaxis also improved. The CFA effectively removed 93% of CG,
without significant removal of IgG, IgM, IgA, albumin, and fibrinogen.
No albumin or fresh frozen plasma (FFP) was required as replacement
fluid for CFA. No citrate toxicity or evidence of complement activation
with the cryofilter was observed.
The entire CFA procedure time (3(1/2) hours) was considered. Intensive,
tandem CFA/HD was performed in a critically ill patient with no apparent
adverse consequences. |
|
Calciphylaxis treated with neurolytic lumbar sympathetic block:
case report and review of the literature.
Green JA, Green CR, Minott SD.
Multidisciplinary Pain Center, the Department of Anesthesiology,
University of Michigan Health Systems, Ann Arbor 48109, USA. |
Reg Anesth Pain Med 2000 May-Jun;25(3):310-2 Abstract quote
BACKGROUND AND OBJECTIVE: Calciphylaxis is a painful complication of
end-stage renal disease and secondary hyperparathyroidism. Calcification
most commonly affects skin and soft tissue of the lower extremities
resulting in excruciatingly painful skin ulcers. Treatment involves
correction of hypercalcemia and hyperphosphatemia, parathyroidectomy,
and supportive measures.
METHODS: The literature and the merits of neurolytic lumbar sympathetic
blockade (LSB) for the treatment of pain associated with calciphylaxis
are reviewed.
CONCLUSIONS: The neurolytic LSB provided pain relief and is a treatment
modality to be considered in managing the pain associated with calciphylaxis. |
|
Is calciphylaxis best treated surgically or medically?
Kang AS, McCarthy JT, Rowland C, Farley DR, van Heerden JA.
Division of Gastroenterologic and General Surgery, Mayo Clinic and
Mayo Foundation, Rochester, MN 55905, USA. |
Surgery 2000 Dec;128(6):967-71;discussion 971-2 Abstract quote
BACKGROUND: Calciphylaxis is a rare, painful, life-threatening problem
of cutaneous necrosis and refractory healing in patients with uremia
and secondary hyperparathyroidism. The pathogenesis involves abnormalities
in calcium and phosphorus metabolism and acute deposition of calcium
in tissues.
METHOD: The clinical course of 16 patients who were diagnosed with
calciphylaxis at our institution from 1994 through 1998 was reviewed.
RESULTS: Fourteen female patients and 2 male patients had chronic renal
disease, secondary hyperparathyroidism, and characteristic skin necrosis
(mean age, 56 years; range, 39-70 years). All patients underwent intensive
medical therapy, including ongoing hemodialysis (n = 16 patients), parathyroidectomy
(n = 7 patients), and debridement of cutaneous lesions (n = 8 patients).
Mean serum values in surgical and nonsurgical patients were significantly
different for phosphorus, calcium-phosphorus product, and parathormone
levels. Median survival was 9.4 months; 15 patients (93%) have died.
The median survival time for parathyroidectomy versus nonparathyroidectomy
was 14.8 and 6.3 months (P =.22), for skin debridement versus nondebridement
was 14.1 and 6.1 months (P =.08), and for diabetic versus nondiabetic
patients was 6.5 and 13.9 months (P =.11).
CONCLUSIONS: Calciphylaxis has a female preponderance, with a dismal
prognosis. A multidisciplinary approach that uses frequent hemodialysis
to normalize calcium and phosphorus levels and local debridement of
skin lesions seems prudent. Parathyroidectomy cannot be recommended
routinely in all patients, unless severe hyperparathyroidism mandates
intervention. |
|
Parathyroidectomy promotes wound healing and prolongs survival in
patients with calciphylaxis from secondary hyperparathyroidism.
Girotto JA, Harmon JW, Ratner LE, Nicol TL, Wong L, Chen H.
Departments of Surgery and Pathology, The Johns Hopkins Medical
Institutions, Baltimore, Md. |
Surgery 2001 Oct;130(4):645-51 Abstract quote
Background. Calciphylaxis is a rare but life-threatening condition
occasionally affecting patients with secondary hyperparathyroidism.
Parathyroidectomy has been advocated as the only potentially curative
intervention.
Methods. Between January 1989 and May 2000, 13 patients with pathologic/clinical
criteria of calciphylaxis were treated at our institution. Of these
13 patients, 7 were managed with medical therapy alone, and 6 were referred
for parathyroidectomy. The medical records were reviewed, and patients/relatives
were interviewed.
Results. All patients had cutaneous wounds requiring local debridement
predominantly located on the lower extremities or abdominal wall. Six
patients underwent subtotal (3.5 gland) parathyroidectomy without morbidity.
All 6 had significant reductions in parathyroid hormone levels after
surgery (mean decrease, 94% +/- 0%), and all reported resolution of
pain and healing of cutaneous wounds. Of the remaining 7 patients who
had medical management alone, 5 eventually died of complications related
to calciphylaxis. In comparing the 2 groups, patients who underwent
parathyroidectomy had a significantly longer median survival than those
who did not have surgery (36 vs 3 months, P =.021).
Conclusions. Calciphylaxis frequently causes gangrene, sepsis, and
eventual death. Parathyroidectomy can be performed with minimal morbidity
and is associated with resolution of pain, wound healing, and a significantly
longer median survival. Therefore, patients with secondary hyperparathyroidism
and signs/symptoms of calciphylaxis should be referred promptly for
consideration of parathyroidectomy. |
| SODIUM THIOSULFATE |
|
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Sodium thiosulphate as a promising therapeutic option to treat calciphylaxis.
-
Department of Dermatology, Johann Wolfgang Goethe University, Frankfurt, Germany.
|
-
Dermatology. 2006;212(4):373-6. Abstract quote
A 35-year-old haemodialysis-dependent woman with chronic renal failure developed large, very painful necrotic ulcers and necrosis on the thighs, buttocks and the abdomen with signs of fast progression. The skin biopsy specimens showed a broad necrosis of the epidermis and thrombosed dermal vessels with focal calcium deposits within the wall. In addition, laboratory findings presented an increased product of serum calcium and phosphate concentrations. Thus, we diagnosed calciphylaxis on the basis of clinical, biochemical and histopathological criteria.
We initiated a therapy in which our patient was treated with intravenous sodium thiosulphate 3 times weekly. Already after 2 weeks of treatment, no new lesions were detectable and there was a dramatic pain relief. In the following 4 weeks, a successive decline of the ulcers and the healing of individual tissue defects could be seen. Four months after the start of the therapy, the patient underwent successful renal transplantation.
Thus, the intravenous therapy of calciphylaxis with sodium thiosulphate might be a new effective alternative in the treatment of this life-threatening disease.
|
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Intraperitoneal sodium thiosulfate for the treatment of calciphylaxis.
-
Division of Nephrology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63110, USA.
|
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Ren Fail. 2006;28(4):361-3. Abstract quote
Calcific uremic arteriolopathy (or calciphylaxis) is a severe complication of renal failure characterized by subcutaneous calcification of the small arteries and tissue necrosis.
We describe the case of a woman receiving continuous cycling peritoneal dialysis with calciphylaxis involving upper and lower extremities. After intolerance of intravenous sodium thiosulfate and limited intravenous access options, we administered sodium thiosulfate intraperitoneally and quantitated the amount of extra calcium removed.
Intraperitoneal administration of sodium thiosulfate was well tolerated and led to removal of extra calcium with peritoneal dialysis.
|
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Long-term intravenous sodium thiosulfate in the treatment of a patient with calciphylaxis.
-
Division of Nephrology and Hypertension, New York Presbyterian Hospital, New York, New York 10021, USA.
|
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Semin Dial. 2005 Sep-Oct;18(5):431-4. Abstract quote
Calciphylaxis is a disabling and life-threatening complication that primarily affects patients who are dialysis dependent. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels, which results in necrotizing, nonhealing ulcers. The development of these lesions portends a grim prognosis, as they are often accompanied by severe and sometimes fatal infectious complications. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor.
We describe an anuric hemodialysis patient who developed severe calciphylaxis that proved refractory to conventional treatment. Following extensive debridement of several wounds, intravenous sodium thiosulfate was utilized as an adjunctive therapy four times a week. Within 6 months, excellent wound healing ensued as well as a dramatic improvement in the lesions that were not previously resected. Aside from occasional nausea, these treatments were well tolerated, despite the development of an anion gap metabolic acidosis. After 34 months of continued treatment the patient remains free from disease recurrence and has demonstrated no untoward effect of prolonged therapy. In an effort to delineate the pharmacokinetics of this drug in a hemodialysis patient, serum thiosulfate levels were obtained 15 minutes after infusion as well as before and after subsequent dialysis treatments.
Consistent with prior studies in anuric canines, we found measurable quantities of the drug more than 50 hours after treatment, in addition to a markedly elevated half life of 478 minutes. However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients.
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