Download Laboratory Features of Cutaneous Lupus Erythematosus

CHAPTER 23
Laboratory Features
of Cutaneous Lupus Erythematosus
Shuntaro Shinada, Daniel J. Wallace
Assuming that patients with cutaneous lupus erythematosus (CLE) do not fulfill the
American College of Rheumatology criteria for systemic LE (SLE) (Tan et al. 1982),
what laboratory features should the clinician look for? Interestingly, there are several.
This chapter attempts to elucidate the laboratory abnormalities associated with CLE,
the most common being hematologic (anemia and leukopenia), erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANAs), and antiphospholipid antibodies. These features are compared with those observed in SLE and certain cutaneous clinical subsets that have been studied.
General Approach to Laboratory Testing
When a dermatologist, family practitioner, internist, or rheumatologist first sees a
patient with CLE, their principal concern should be to rule out evidence of systemic
disease. After all, 15% of patients with CLE progress to SLE in 10–15 years of observation (Rowell 1984). In addition to a complete medical history and physical examination, clinical laboratory findings can be very helpful in this regard. Specifically, a
blood chemistry panel allows screening for renal or hepatic involvement. Creatine
phosphokinase testing assists in ruling out muscle inflammation. Evidence for
autoimmune hemolytic anemia or thrombocytopenia is looked for in the complete
blood cell count as well as in the lactic dehydrogenase, reticulocyte count, Coombs’
direct antibody testing, serum haptoglobin, and antiplatelet antibodies. A routine
urinalysis free of cellular casts or protein makes it highly unlikely that the kidney is
involved. Specific autoantibodies, almost never observed in CLE, if found, can suggest
central nervous system disease (antiribosomal P, antineuronal), mixed connective tissue disease (anti-RNP), or other disease subsets. In our practice, all patients have
annual chest radiographs and electrocardiograms, since there are no blood tests to
screen for cardiac or pulmonary involvement. Finally, additional imaging or electrical tests (electromyography, nerve conduction studies, 2-D echocardiography with
Doppler) are occasionally ordered, and the results should be normal in CLE. If
not, muscle, nerve, cardiac, or pulmonary disease representing visceral involvement
should be ruled out.
This chapter assumes that the presence of systemic disease is not under consideration. The question remains, are there any laboratory tests worth ordering to monitor or better characterize CLE?
23
312
Shuntaro Shinada, Daniel J. Wallace
Medications Used to Manage Cutaneous Lupus
Erythematosus Warrant Periodic Laboratory Monitoring
Although the different therapeutic options for CLE are discussed in later chapters, it
is valuable to note the laboratory abnormalities associated with the medications used
to treat CLE (Table 23.1).
Table 23.1. Laboratory abnormalities associated with use of drugs for cutaneous lupus erythe-
matosus
Medication
Laboratory side effects
Laboratory monitoring
Antimalarials
Chloroquine
Monitor CBC, serum creatinine,
Hemolysis secondary to
and LFT every 2 months
G-6-PD deficiency, decreased
creatinine clearance
Hydroxychloroquine Decreased creatinine clearance, decreased cholesterol
profile, agranulocytosis (rare)
Quinacrine
Aplastic anemia
Antileprosy drugs
Dapsone
Thalidomide
Sulfhemoglobinemia, methemoglobinemia, hemolysis
secondary to G-6-PD deficiency, hepatotoxicity
Highly teratogenic, neutropenia
Monitor baseline G-6-PD levels.
Monitor CBC every 2 weeks for the
first 3 months, then every 2 months
thereafter
Monitor baseline LFTs then every 2
months thereafter
Baseline pregnancy test, then
weekly for the first month, then
monthly thereafter
Monitor CBC every 2 months
Methotrexate
Blood dyscrasias, hepatotoxicity
Monitor baseline LFTs, CBC, serum
creatinine, then weekly until dose
stabilized, then every 1–2 months
thereafter
Cyclosporine
Increased serum creatinine
level
Monitor 2 baseline creatinines, then
every 2 weeks for the first 3 months,
then every month thereafter
Azathioprine
Thrombocytopenia, neutropenia, hepatotoxicity
Monitor baseline CBC, LFTs, then
every 2 weeks for the first month,
then every 1–3 months thereafter
Glucocorticosteroids
Increased serum glucose
level; increased VLDL-C,
HDL-C, and TG levels
Monitor baseline lipid panel, CBC,
serum glucose and potassium, then
monitor serum/urine glucose every
3–6 months
CBC, complete blood cell count; G-6-PD, glucose-6-phosphate dehydrogenase; HDL-C, highdensity lipoprotein cholesterol; LFTs, liver function tests; TG, triglyceride; VLDL-C, very-lowdensity lipoprotein cholesterol.
Laboratory Features of Cutaneous Lupus Erythematosus
313
Antimalarials
The three antimalarials available at this time for the treatment of CLE are chloroquine,
hydroxychloroquine, and quinacrine. Overall, these drugs are relatively safe, but there
are some laboratory abnormalities to consider. Chloroquine slightly decreases creatinine levels in half of its users, most likely by raising plasma aldosterone levels (Musabayane 1994). Forty-five percent of hydroxychloroquine is excreted in the kidneys, and
the drug is associated with up to a 10% decrease in creatinine clearance (Landewe et
al. 1995). Therefore, the dosage should be adjusted for patients with renal impariment.
Antimalarials also have a beneficial antihyperlipidemic effect. Hydroxychloroquine
induces a 15%–20% decrease in total cholesterol, triglyceride, and LDL levels (Wallace
et al. 1990). It is associated with only one case of agranulocytosis, in a patient who was
given 1,200 mg daily,which is up to six times the current recommended dosage (Polano
et al. 1965), and a handful of case reports of various blood dyscrasias, such as aplastic
anemia, leukopenia, thrombocytopenia, and hemolysis in individuals with glucose-6phosphate dehydrogenase (G-6-PD) deficiency.
Chloroquine has been implicated in rare reports of G-6-PD deficiency hemolysis
(Choudhry et al. 1978) and with agranulocytosis (Kersly and Palin 1959). Since chloroquine is known to concentrate in the liver, it should be used with caution in patients
with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs.
The prevalence of aplastic anemia among US soldiers in the Pacific during World
War II rose from 0.66 to 2.84 per 100,000 after quinacrine’s introduction (Custer
1946). This represented 58 patients, 48 of whom received quinacrine. Of these, 16 were
associated with overdoses, and two received marrow-suppressant drugs concurrently
(Wallace 1989). It is therefore recommended that patients receiving antimalarial
treatment have a complete blood cell count and a serum creatinine test every few
months during therapy. Patients taking chloroquine or hydroxychloroquine should
undergo ophthalmologic examination at 6- or 12-month intervals, respectively.
Antileprosy Drugs
Dapsone
Dapsone’s use is limited by its toxic effects, which include sulfhemoglobinemia and
methemoglobinemia, a dose-related hemolytic anemia, a “dapsone hypersensitivity
syndrome,” and aplastic anemia (Meyerson and Cohen 1994, Mok et al. 1998). All
patients treated with dapsone should have their baseline G-6-PD level checked. The
drug should not be given to patients with low levels. Complete blood cell counts
should be checked every 2 weeks for the first 3 months, then every 2 months thereafter. Toxic hepatitis and cholestatic jaundice have been reported early in therapy.
Hyperbilirubinemia may occur more often in G-6-PD-deficient patients. Baseline and
subsequent monitoring of liver function is recommended.
Thalidomide
Thalidomide is a highly teratogenic drug with antileprosy and antilupus effects via
various mechanisms.Side effects include teratogenicity,fatigue,dizziness,weight gain,
constipation, amenorrhea, dry mouth, and a non-dose-related polyneuropathy that is
associated with chronic administration (Ludolph and Matz 1982). Because thalido-
314
Shuntaro Shinada, Daniel J. Wallace
mide is so highly teratogenic, women of childbearing potential should have pregnancy
testing. The test should be performed within 24 h of beginning thalidomide therapy
and at regular intervals when appropriate.Pregnancy testing should also be performed
if a patient misses her period or if there is any abnormality in menstrual bleeding.
Decreased white blood cell counts, including neutropenia, have been infrequently
reported in association with the clinical use of thalidomide. White blood cell count
and differential should be monitored on an ongoing basis, especially in patients who
may be more prone to neutropenia. Higher doses of thalidomide may predispose
patients to coagulopathies.
Methotrexate
Although serious and sometimes fatal blood dyscrasias are a well-known consequence of high-dose methotrexate therapy, the Committee on Safety of Medicines in
the United Kingdom (Dodd et al. 1985) stated in September 1997 that it was also
aware of 83 reports of blood dyscrasias associated with low-dose methotrexate used
to treat psoriasis or rheumatoid arthritis; there were 36 fatalities. Megaloblastic
anaemia, usually with marked macrocytosis, has been reported in mainly elderly
patients receiving long-term weekly methotrexate therapy (Dahl 1984).
Methotrexate has been associated with periportal fibrosis and cirrhosis (Neuberger 1995), and its potential for hepatotoxicity has been a source of some concern
given its use in nonmalignant disorders such as psoriasis and rheumatoid arthritis. It
is recommended that liver function tests (LFTs) (as well as blood cell counts and renal
function tests) be checked before beginning therapy then repeated weekly until therapy is stabilized, and thereafter every 2–3 months (Committee on Safety of Medicines/Medicines Control Agency 1994). The American College of Rheumatology recommends checking baseline LFTs, along with complete blood cells counts, creatinine
levels, and hepatitis B and C serologies, before initiating treatment; then, at intervals
of 4–8 weeks, LFTs should be monitored (Kremer et al. 1994). Methotrexate should be
used with great care in patients with bone marrow, hepatic, or renal impairment.
Methotrexate is a potent teratogen, and its use should be avoided in pregnancy.
Cyclosporine
Before initiating treatment, a careful physical examination, including blood pressure
measurements (on at least two occasions) and two creatinine levels to estimate baseline
status should be performed. Blood pressure and serum creatinine levels should be evaluated every 2 weeks during the initial 3 months and then monthly if the patient is stable.
It is advisable to monitor serum creatinine levels and blood pressure always after an
increase of the dose of nonsteroidal anti-inflammatory drugs and after initiation of new
nonsteroidal anti-inflammatory drug therapy in those receiving cyclosporine treatment.
Azathioprine
Thrombocytopenia and leukopenia are dose dependent and may be reversed by
reducing the dose or temporarily discontinuing use of azathioprine. Other reported
hematologic adverse effects include eosinophilia, leukocytosis, neutropenia, anemia,
aplastic anemia, and fatal myelogenous leukemia.
Laboratory Features of Cutaneous Lupus Erythematosus
315
Results of one small study suggest that analysis of thiopurine methyltransferase
genotype may allow identification of patients who are at risk for azathioprine hematologic toxic effects. The authors consider testing to be cost-effective compared with
the cost of blood monitoring and supportive care for the 2%–12% of patients with
this toxic effect (Black et al. 1998).
Data from the National Cooperative Crohn’s Disease Study identified six patients
(5.3%) with pancreatitis who were treated with azathioprine alone (Sturdevant et al.
1979). Associated symptoms include abdominal pain, elevated amylase and lipase
levels, and vomiting.
Azathioprine can be hepatotoxic, and associated symptoms may include anorexia,
nausea, fatigue, weight loss, jaundice, pruritis, dark urine, and elevated LFTs. Ideally,
LFTs should be monitored every 2 weeks for the first 4 weeks and every 1–3 months
thereafter (Gaffney and Scott 1998).
Glucocorticosteroids
Glucocorticoids (GCs) induce insulin synthesis but oppose its effects on glucose
metabolism, thus predisposing to or exacerbating, if present, diabetes mellitus. These
effects take place because of decreased peripheral utilization of glucose and increased
gluconeogenesis induction in the liver. GC enhances effects on lipolysis and protein
catabolism, thus increasing the substrates for gluconeogenesis (Schimmer and Parker
1996). GCs have an impact on lipid metabolism by enhancing the lipolytic effect of
catecholamines and growth hormone, and they induce a centripetal body fat redistribution (Orth and Kovacs 1998). One study showed that the administration of prednisone for 14 days in healthy men increased the levels of very-low-density lipoprotein
cholesterol, high-density lipoprotein cholesterol, and triglycerides (Ettinger and Hazzard 1988). Another study showed that increasing the prednisone dose by 10 mg daily
was associated with a 7.5-mg/dL increase in cholesterol levels (Petri et al. 1994). GCs
induce peripheral neutrophilia and elevate white blood cell counts by reducing neutrophil migration to tissues (Boumpas et al. 1993). Because of these effects of GCs,
before starting therapy, it is recommended to check the baseline lipid panel (total
cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels), complete blood cell count, and serum glucose and
potassium levels. Thereafter, serum or urine glucose levels should be checked every
3–6 months. Since corticosteroids promote the excretion of water, some of its
mineralocorticoid effects include hypokalemia, which should also be monitored.
Specific Laboratory Tests that Can Be Abnormal
in Cutaneous Lupus Erythematosus
Please refer to Tables 23.2 and 23.3.
Hematologic Abnormalities
Hematologic abnormalities are common in SLE and may often be its presenting
manifestation. Although hematologic abnormalities are seen in CLE, they are not as
316
Shuntaro Shinada, Daniel J. Wallace
Table 23.2. Laboratory Differences Between the various subtypes of cutaneous lupus erythe-
matosus (CLE). Modified from Sontheimer and Provost 1997
Disease features
ACLE
SCLE
DLE
Antinuclear antibodies
Ro/SSA antibodies
By immunodiffusion →
By ELISA →
Antinative DNA antibodies
Hypocomplementemia
Risk for developing SLE
+++
++
+
+
++
+++
+++
+++
+++
+++
+
+
++
0
+
0
+
+
ACLE, acute CLE; DLE, discoid LE; ELISA, enzyme-linked immunosorbent assay; SCLE, subacute CLE; SLE, systemic LE.
+++, strongly associated; ++, moderately associated; +, weakly associated; 0, negative, no association.
common as in SLE. Patients with CLE had anemia ranging from 2% to 27% of the
time, whereas patients with SLE had anemia 30% of the time. Eight percent of
patients with SLE have hemolytic anemia, whereas it does not occur in patients with
CLE (Pistiner et al. 1991). Between 0% and 30% of patients with CLE have leukopenia
vs 51% of patients with SLE. Thrombocytopenia occurs in 2%–4% of patients with
CLE as opposed to in 16% of those with SLE.
Erythrocyte Sedimentation Rate
The ESR is a nonspecific marker for increased immunologic activity and is often time
elevated in various types of inflammatory processes. The ESR is elevated in 20%–56%
of patients with CLE, whereas it is elevated in most patients with SLE.
Antinuclear Antibodies
The ANA test is a helpful serologic marker in the diagnosis of LE and other rheumatologic conditions. Approximately 96% of patients with SLE are positive for ANA,
whereas 4%–63% of patients with CLE are positive for ANA. When reference laboratories switched from using animal substrates to the HEp-2 cell line in the mid-1980s
to detect ANA, many ANA-negative patients became positive. This may help explain
why in studies done earlier than the mid-1980s, patients with CLE had lower ANA
positivity rates than in those done after the mid-1980s.
Anticardiolipin Antibodies
The anticardiolipin antibody is one of the serologic markers used to diagnose the
antiphospholipid syndrome. The anticardiolipin antibody was positive in 31% of
patients with CLE, whereas in patients with SLE its prevalence is slightly higher.
Although anticardiolipin antibody is seen in 30%–40% of patients with SLE and CLE,
it has not been associated with any complications (e. g., spontaneous abortions or
arterial and/or venous occlusive disease) in CLE (Mayou et al. 1988).
6
–
–
45
1
–
–
56
20
–
13
–
92 CLE
1979
27
–
12
4
25
–
–
–
Millard and
Rowell 1979
43
–
21
–
56 CLE
1982
0
0
10
–
22
0
4
5
Callen
1982
ANAs, antinuclear antibodies; ds, double-stranded; RF, rheumatoid factor.
69 CLE
1978
10
–
14
–
49
–
0
–
80 CLE
1975
2
–
0
–
4
8
0
–
Cases (n)
Year
Anemia (%)
Hemolytic anemia (%)
Leukopenia (%)
Thrombocytopenia (%)
Positive ANAs (%)
Low C3 (%)
High anti-ds-DNA (%)
Positive anti-RNP (%)
Positive RF
(latex fixation) (%)
Positve anti-RoSSA (%)
Positive anticardiolipin
antibody (%)
High sedimentation
rate (%)
O’Loughlin
et al. 1978
Prystowski
et al. 1975
Parameter
31
31
9
4
67 CLE
1990
7
0
30
2
63
10
8
2
54
38
23
18
464 SLE
1991
30
8
51
16
96
39
40
14
0.001
0.53
0.02
0.003
1991
0.0001
0.009
0.002
0.0001
0.0001
0.0001
0.0001
0.081
Wallace et al. Pistiner et al. CLE vs SLE
1992
1991
P Value, Wallace
et al. 1992
Table 23.3. Laboratory data comparing cutaneous lupus erythematosus (CLE) and systemic LE (SLE)
56
–
–
–
245 CLE
1997
–
–
–
–
29
–
35
–
Tebbe et al.
1997
Laboratory Features of Cutaneous Lupus Erythematosus
317
318
Shuntaro Shinada, Daniel J. Wallace
Anti-Ro/SSA Antibody
Anti-Ro/SSA antibodies are present in the serum of patients with SLE and Sjögren’s
syndrome and in 1 in 1,000 healthy people. The anti-Ro/SSA antibody is directed
against ribonucleoproteins consisting of a 60-kDa peptide and an antigenically distinct 52-kDa polypeptide. Positive anti-Ro/SSA antibody has been seen in 4% of
patients with CLE, whereas in patients with SLE the prevalence is 18%–30%, depending on whether immunoblotting or double diffusion methods are used. In a 1998
report by Chelbus et al. (Chelbus et al. 1998), there was similar frequency of both antiRo/SSA and anti-La/SSB in subacute cutaneous LE (SCLE) and SLE (approximately
70%). In another study, approximately 75% of patients with SCLE had anti-Ro/SSA
precipitins (Sontheimer et al. 1982). Patients with SCLE have higher prevalence and
titers of antibodies to both native 60-kDa Ro/SSA and 52-kDa Ro/SSA than those with
chronic CLE (Lee et al. 1994).
Anti-double-stranded DNA Antibodies
Autoantibodies to DNA are classically associated with SLE. Wallace et al. (Wallace et
al. 1992) reported that 4%–8% of patients with CLE had high anti-double-stranded
(ds) DNA antibodies (Farr assay) as opposed to 40% with SLE. Chelbus et al. (Chelbus et al. 1988) noted that 1.2% of patients with SCLE had high anti-ds-DNA antibodies compared with 34% of patients with SLE.
Abnormal Testing Associated
with Cutaneous Lupus Erythematosus Subsets
Acute Cutaneous Lupus Erythematosus
ACLE refers to the acute inflammatory rashes in patients with SLE and as such, has
not been studied as a separate entity. Wysenbeek et al. (Wysenbeek et al. 1992) noted
that the nonspecific “rash” of SLE was associated with the presence of anti-ds-DNA
antibodies and low serum complement.
Chronic Cutaneous Lupus Erythematosus
Only a few patients with chronic CCLE without evidence of systemic involvement will
have autoantibodies (Prystowsky et al. 1975). Of patients with CCLE, 30%–40% may
exhibit low titers of ANA. However, fewer than 5% of patients with CCLE will have the
higher levels of ANA that are seen in patients with severe SLE. Antibodies to singlestranded DNA are fairly common in CCLE, whereas antibodies to ds-DNA are uncommon (Callen et al. 1985). Patients whose disease course is dominated by discoid LE
(DLE) lesions and who have evidence of mild SLE and overlapping connective tissue
disease occasionally have precipitating antibodies to U1RNP (Callen 1982).Sometimes
precipitating antibodies to Ro/SSA are seen in CCLE (Lee et al. 1994), and less frequently precipitating La/SSB and Sm antibodies (Provost and Ratrie 1990). Less than
10% of patients with CCLE have IgG isotype cardiolipin antibodies (Mayou et al.1988).
Laboratory Features of Cutaneous Lupus Erythematosus
319
A small percentage of patients with CCLE will have a false-positive serologic test for
syphilis (VDRL), positive rheumatoid factor, slight depression of serum complement
levels, modest elevations in gamma globulin levels, or modest leukopenia.
Subacute Cutaneous Lupus Erythematosus
SCLE occurs in 7%–27% of patients with LE (Cohen and Crosby 1994). Studies have
shown that SCLE occurs mostly in white female patients in all age groups. Of patients
with SCLE, 60%–81% have positive ANAs when human tissue substrate is used
(Callen and Klein 1988). With immunodiffusion techniques, anti-Ro/SSA antibodies
have been detected in 40%–100% of patients with SCLE (Lee et al. 1994). Anti-La/SSB
antibodies by gel double diffusion have been observed in 12%–42% of patients with
SCLE (Johansson-Stephansson et al. 1989). However, higher percentages of antiLa/SSB antibody levels have been seen in several studies outside the United States
(Shou-yi et al. 1987). It has been reported that patients with SCLE have anti-ds-DNA
at a prevalence of 1.2% (Chelbus et al. 1998).
A false-positive syphilis serologic test result is detected in 17%–33% of patients
with SCLE (Sontheimer 1989), and ca. 10%–16% of patients with SCLE have anticardiolipin antibodies (Fonesca et al. 1992). Rheumatoid factor is present in approximately one third of patients (Sontheimer 1989). Only 10% of patients with SCLE have
anti-ds-DNA, anti-SmRNP, or anti-U1RNP antibodies (Sontheimer 1989). Approximately one third of patients with SCLE have antilymphocyte antibodies, and
18%–44% of patients with SCLE are reported to possess antithyroid antibodies
(Callen et al. 1986, Konstadoulakis et al. 1993).
Other Cutaneous Lupus Erythematosus Subsets
Lupus Erythematosus Profundus/Lupus Erythematosus Panniculitis
LE profundus/LE panniculitis is another rare form of CCLE characterized by inflammatory lesions in the lower dermis and the subcutaneous tissue. Of these patients,
70%–75% have positive ANA, but anti-ds-DNA antibodies are uncommon (Sanchez
et al. 1982).
Chilbain Lupus Erythematosus/Lupus Pernio
Chilbain LE/lupus pernio is another variant of CLE consisting of red-purple patches
and plaques on patients’ faces, fingers, and toes that are precipitated by cold, damp
climates. One study in 1998 found that eight of nine patients with chilbains lupus had
anti-Ro/SSA antibodies (Franceschini et al. 1998). Most of these patients also complained of photosensitivity and Raynaud’s phenomenon.
Lupus Erythematosus Tumidus (LET), Hypertrophic Lupus Erythematosus,
Mucosal Lupus Erythematosus
LE tumidus (LET) is a subset of CLE seen when there is excessive accumulation of
dermal mucin early in the course of a CLE lesion. The result is edematous, urticarialappearing plaques of LE tumidus. Hypertrophic HLE (i.e., hyperkeratotic HLE, verrucous HLE) is a rare variant of CLE in which the hypekeratosis that is usually present in classic DLE is greatly exaggerated. Mucosal DLE is a variant of chronic
320
Shuntaro Shinada, Daniel J. Wallace
cutaneous DLE involving most frequently the oral mucosa, as well as the nasal, conjunctival, and genital mucosal surfaces. The laboratory features of these three subsets
of CLE are not well delineated.
Laboratory Testing and Progress to Dissemination
of Systemic Lupus Erythematosus
Approximately 15% of patients with CLE eventually progress to SLE (Rowell 1984).
Several studies have been undertaken to determine the clinical and laboratory features that may predict such a pattern of disease progression. Clinically, patients with
generalized DLE are at higher risk of developing SLE, oftentimes with more severe
manifestations (Callen 1982). Laboratory tests associated with the development of
SLE in patients with DLE include severe leukopenia, unexplained anemia, false-positive serologic tests for syphilis, persistently positive, high-titer ANA, anti-singlestranded DNA antibody, hypergammaglobulinemia, an elevated ESR greater than
50 mm/h, and a positive lupus band test (Callen 1982). A study in 1997 showed that
in SCLE and/or DLE, patients with evidence of nephropathy, arthralgias, or ANA titer
of 1:320 were at significantly higher risk of having systemic disease (Tebbe et al.
1997). This study did not find ESR and anti-ds-DNA antibodies to be useful in distinguishing patients with or without systemic disease. Another recent study suggests
that elevated soluble interleukin 2 receptor levels might correlate with patients with
SLE and discoid lupus lesions (Blum et al. 1993).
Summary and Recommendations
Although there are laboratory features that are more prevalent in CLE vs SLE, there are
no specific serologic tests that differentiate the two diseases. Clinical correlation is
indispensable in distinguishing them. There are also important laboratory values that
need to be monitored at the onset and during treatment of CLE with medications.
References
Black AJ, McLeod HL, Capell HA, Powrie RH, Matowe LK, Pritchard SC, Collie-Duguid ES, Reid
DM (1998) Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity
from azathioprine. Ann Intern Med 129:716–718
Blum C,Zillikens D,Tony HP,Hartmann AA,Burg A (1993) Soluble interleukin-2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus. Hautarzt 44:290–295
Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE (1993) Glucocorticoid therapy for
immune-mediated diseases: basic and clinical correlates. Ann Intern Med 119:1198–1208
Callen JP (1982) Chronic cutaneous lupus erythematosus: clinical, laboratory, therapeutic, and
prognostic examination of 62 patients. Arch Dermatol 118:412–416
Callen JP, Klein J (1988) Subacute cutaneous lupus erythematosus. Clinical, serologic, immunogenetic, and therapeutic considerations in 72 patients. Arthritis Rheum 31:1007–1013
Callen JP,Fowler JF,Kulick KB (1985) Serologic and clinical features of patients with discoid lupus
erythematosus: relationship of antibodies to single-stranded deoxyribonucleic acid and of
other antinuclear antibody subsets to clinical manifestations. J Am Acad Dermatol 13:748–755
Laboratory Features of Cutaneous Lupus Erythematosus
321
Callen JP, Kulick KB, Stelzer G, Fowler JF (1986) Subacute cutaneous lupus erythematosus. Clinical, serologic, and immunogenetic studies of 49 patients seen in a non-referral setting. J Am
Acad Dermatol 15:1227–1237
Chelbus E, Wolska H, Blaszyk M, Jablonska S (1998) Subacute cutaneous lupus erythematosus
versus systemic lupus erythematosus: diagnostic criteria and therapeutic implications. J Am
Acad Dermatol 38:405–412
Choudhry V, Madan N, Sood SK, Ghai OP (1978) Chloroquine-induced haemolysis and acute
renal failure in subjects with G-6-PD deficiency. Trop Geogr Med 30:331–335
Cohen MR, Crosby D (1994) Systemic disease in subacute cutaneous lupus erythematosus: a
controlled comparison with systemic lupus erythematosus. J Rheumatol 21:1665–1669
Committee on Safety of Medicines/Medicines Control Agency (1997) Blood dyscrasias and
other ADRs with low-dose methotrexate. Current Problems 23:12–18
Custer RP (1946) Aplastic anemia in soldiers treated with Atabrine (quinacrine). Am J Med Sci
212:211–224
Dahl MGC (1984) Folate depletion in psoriatics on methotrexate. Br J Dermatol 111(Suppl 26):18
Dodd HJ, Kirby JD, Munro DD (1985) Megaloblastic anaemia in psoriatic patients treated with
methotrexate. Br J Dermatol 112:630–631
Ettinger WH, Hazzard WR (1988) Prednisone increases very low density lipoprotein and high
density lipoprotein in healthy men. Metabolism 37:1055–1058
Fonseca E, Alvarez R, Gonzalez MR, Pascual D (1992) Prevalence of anticardiolipin antibodies in
subacute cutaneous lupus erythematosus. Lupus 1:265–268
Franceschini F, Calzavara-Pinton P, Quinzanini M, Cavazzana I, Bettoni L, Zane C, Facchetti F,
Airo P, McCauliffe DP, Cattaneo R (1998) Chilbains lupus erythematosus is associated with
antibodies to SSA/Ro. Lupus 8:215–219
Gaffney K, Scott DG (1998) Azathioprine and cyclophasphamide in the treatment of rheumatoid
arthritis. Br J Rheum 37:824–836
Johansson-Stephansson E, Koskimes S, Partanen J, Kariniemi AL (1989) Subacute cutaneous
lupus erythematosus: genetic markers and clinical and immunological findings in patients.
Arch Dermatol 125:791–796
Kersley GD, Palin AG (1959) Amodiaquine and hydroxychloroquine in rheumatoid arthritis.
Lancet ii:886–888
Konstadoulakis MM, Kroubouzos G, Tosca A, Piperingos G, Marafelia P, Konstadoulakis M,
Varelzidis A, Koutras DA (1993) Thyroid autoantibodies in the subsets of lupus erythematosus: correlation with other autoantibodies and thyroid function. Thyroidol Clin
Exp 5:1–7
Kremer JM, Alarcon GS, Lightfoot RW Jr, Willkens RF, Furst DE, Williams HJ, Dent PB, Weinblatt
ME (1994) Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver
toxicity. American College of Rheumatology. Arthritis Rheum 37:1829–1830
Landewe RB, Vergouwen MS, Goeei The SG, Van Rijthoven AW, Breedveld FC, Dijkmans BA
(1995) Antimalarial drug induced decrease in creatinine clearance. J Rheumatol 22:34–37
Lee LA, Roberts CM, Frank MB, McCubbin VR, Reichlin M (1994) The autoantibody response to
Ro/SSA in cutaneous lupus erythematosus. Arch Dermatol 130:1262–1268
Ludolph A, Matz DR (1982) Electrophysiologic changes in thalidomide neuropathy under treatment for discoid LE. EEG EMG 13:167–170
Mayou SC, Wojnorowska F, Lovell CR, Asherson RA, Leigh IM (1988) Anticardiolipin and antinuclear antibodies in discoid lupus erythematosus – their clinical significance. Clin Exp Dermatol 13:389–392
Meyerson MA, Cohen PR (1994) Dapsone-induced aplastic anemia in a woman with bullous systemic lupus erythematosus. Mayo Clin Proc 69:1159–1162
Millard LG, Rowell NR (1979) Abnormal laboratory test results and their relationship to prognosis in discoid lupus erythematosus. A long-term follow-up study of 92 patients. Arch Dermatol 115:1055–1058
Mok CC, Lau CS, Woon Sing Wong R (1998) Toxicities of dapsone in the treatment of cutaneous
manifestations of rheumatic diseases. J Rheumatol 25:1246–1247
322
Shuntaro Shinada, Daniel J. Wallace
Musabayane CT, Ndhlovu CE, Balment RJ (1994) The effects of oral chloroquine administration
on kidney function. Renal Fail 16:221–228
Neuberger J (1995) Methotrexate and liver disorders. Prescribers’ J 35:158–63
O’Loughlin S, Schroeter AL, Jordan RE (1978) A study of lupus erythematosus with particular
reference to generalized discoid lupus. Br J Dermatol 99:1–11
Orth DN,Kovacs WJ (1998) The adrenal cortex.In: Wilson JD,Foster DW,Kronenberg HM,Larsen
PR (eds) Williams textbook of endocrinology, 9th ed. WB Saunders, Philadelphia, pp 517–664
Petri M, Lakatta C, Magder L, Goldman D (1994) Effects of prednisone and hydroxychloroquine
on coronary artery disease rise factors in systemic lupus erythematosus: a longitudinal data
analysis. Am J Med 96:254–259
Pistiner M, Wallace DJ, Nessim S, Metzger AL, Klinenberg JR (1991) Lupus erythematosus in the
1980s: a survey of 570 patients. Semin Arthritis Rheum 21:55–64
Polano MK, Cats A, van Olden GAJ (1965) Agranulocytosis following treatment with hydroxychloroqine sulfate. Lancet 1:1275
Provost TT, Ratrie H (1990) Autoantibodies and autoantigens in lupus erythematosus and Sjogren’s syndrome. Curr Probl Dermatol 2:150–208
Prystowsky SD, Kerndon JH, Gilliam JN (1975) Chronic cutaneous lupus erythematosus (DLE):
a clinical and laboratory investigation of 80 patients. Medicine 55:183–191
Rowell NR (1984) The natural history of lupus erythematosus. Clin Exp Dermatol 9:217–231
Sanchez NP, Peters MS, Winkelmann RK (1981) The histopathology of lupus erythematosus
panniculitis. J Am Acad Dermatol 5:673–680
Schimmer BP, Parker KL (1996) Adrenocorticotropic hormone; adrenocortical steroids and
their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones.
In: Hardman JE, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (eds) The pharmacological basis of therapeutics, 9th ed. McGraw-Hill, New York, pp 1459–1485
Shi SY, Feng SF, Liao KH, Fang L, Kang KF (1987) Clinical study of 30 cases of subacute cutaneous
lupus erythematosus. Chin Med J 100:45–48
Sontheimer RD (1989) Subacute cutaneous lupus erythematosus: a decade’s perspective. Med
Clin North Am 73:1073–1090
Sontheimer RD, Provost TT (1997) Cutaneous manifestations of lupus erythematosus. In: Wallace DJ, Hahn BH (eds) Dubois’ lupus erythematosus, 5th ed. Williams & Wilkins, Philadelphia, pp 569–623
Sontheimer RD, Maddison PJ, Richlin M, Jordon RE, Stasny P, Gilliam JN (1982) Serologic and
HLA associations in subacute cutaneous lupus erythematosus: a clinical subset of lupus erythematosus. Ann Intern Med 97:664–671
Sturdevant RA, Singleton JW, Derern JL, Law DH, McCleery JL (1979) Azathioprine-related pancreatitis in patients with Crohn’s disease. Gastroenterology 77:883–886
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester
RJ (1982) Special article: the 1982 revised criteria for the classification of systemic lupus
erythmatosus. Arthritis Rheum 25:1271–1277
Tebbe B, Mansmann U, Wollina U, Auer-Grumbach P, Licht-Mbalyohere A, Arensmeier M,
Orfanos CE (1997) Markers in cutaneous lupus erythematosus indicating systemic involvement – a multicenter study on 296 patients. Acta Derm Venereol 77:305–308
Wallace DJ (1989) The use of quinacrine (Atabrine) in rheumatic diseases: a reexamination.
Semin Arthritis Rheum 18:282–296
Wallace DJ, Metzger AL, Stecher VJ, Turnbull BA, Kern PA (1990) Cholesterol-lowering effects of
hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of
steroids on lipids. Am J Med 89:322–326
Wallace DJ, Pistiner M, Nessim S, Metzger AL, Klinenberg JR (1992) Cutaneous lupus erythematosus without systemic lupus erythematosus: clinical and laboratory features. Semin
Arthritis Rheum 21:221–226
Winkelmann RK, Peters MS (1982) Lupus panniculitis. Dermatol Update 135
Wysenbeek AJ, Guedj D, Amit M, Weinberger A (1992) Rash in systemic lupus erythematosus:
prevalence and relation to cutaneous and non-cutaneous disease manifestations. Ann
Rheum Dis 51:717–719