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Tuberculosis cutis colliquativa during long-term immunosuppressive therapy for rheumatoid arthritis.

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Vol. 40, No. 1, January 1997, pp 188-190
0 1997, American College of Rheumatology
With the widespread use of immunosuppressive
therapy in autoimmune disorders, an increased incidence of infectious disease has been observed (1). A
number of emerging opportunistic pathogens are hazardous to severely immunocompromised patients (2).
The most common infectious disease, affecting approximately one-third of the world population, is tuberculosis
(3). The clinical spectrum of infection with Mycobacterium tuberculosis involves pulmonary and cutaneous
disease (1). In contrast to developing countries, cutaneous manifestations of tuberculosis (tuberculosis cutis
colliquativa or scrofuloderma, lupus vulgaris, tuberculosis verrucosa cutis) have been rare in industrialized
nations in the last 3 decades (3,4). In a postmortem study
of 161 patients with rheumatoid arthritis (RA), evidence
of extrapulmonary miliary tuberculosis was found in
3.7%. None of these cases was detected clinically (5).
Tuberculosis cutis colliquativa typically develops per
continuum from lymph node tuberculosis (6). In rare
cases, other organ manifestations, such as tuberculosis
of the bones, joints, or even the liver, may serve as the
origin for direct spread to the subcutis (7).
Herein we report a case of tuberculosis cutis
colliquativa that probably did not develop per continuum, but as a result of miliary dissemination. An elderly
woman developed scrofuloderma after long-term
immunosuppressive therapy for RA. Clinical, histopathologic, and bacteriologic features and therapeutic
strategies are presented.
G.-C. Sutor, MD, J. Ockenga, MD, P. Kirschner, MD, C.
Schatzle, MD, M. Mendila, MD, M. Jendro, MD, M. Stoll, MD, E.
Bottger, R. E. Schmidt: Medical School of Hannover, Hannover,
Address reprint requests to G.-C. Sutor, MD, Department of
Medicine, Division of Clinical Immunology, Medical School of Hannover, D-30623 Hannover, Germany.
Submitted for publication March 12,1996; accepted in revised
form April 15, 1996.
The patient, a 75-year-old woman, had been
diagnosed with seropositive RA in 1989. She presented
with erosive and destructive symmetric arthritis mainly
localized in the distal joints. Steroid treatment led to
marked improvement, but the disease relapsed and
pericarditis developed after reduction of the dosage.
Therefore, sulfasalazine was added to the treatment
regimen and was given for 7 months, after which it was
discontinued because of lack of efficacy. Subsequent
treatment included gold therapy for 10 months, followed
by methotrexate for 14 months (both discontinued because of lack of efficacy), and then azathioprine for 20
months. However, the concomitant steroid treatment
could not be substantially reduced. Type IIb insulindependent diabetes mellitus was diagnosed, and the
patient was admitted to the hospital because of increasing and varied clinical symptoms. Included among these
was newly developed spinal pain which, on the basis of
radiographic findings,was attributed to osteochondrosis.
At this time, immunosuppressive medication consisted of
azathioprine, 150 mg/day, and prednisolone, 20 mgjday.
At admission, the patient was overweight (height
1.53 meters, weight 75 kg) and had oral thrush, hepatomegaly, postarthritic arthrosis most prominent at the
lower extremities, and diffuse pain of her muscles. On
the left side of the lower abdominal wall were 5 erythematous, indurated lesions up to 3 cm in diameter. Similar
lesions were noted on the right thigh. There was no
fever, and the patient denied having night sweats. She
did report the occurrence of an occasional dry cough
that had not changed over the previous few months. The
gamma glutamyl transferase level was 52 units/liter
(normal <18), the glumatic dehydrogenase level was 4
units/liter (normal <3), the a,-globulin level was 14%
(normal <11%), the C-reactive protein level was 74
mgjliter (normal <8), and the serum iron level was 4
pmoles/liter (normal >14). The remainder of the laboratory data were normal.
Figure 1. Cutaneous and subcutaneous abdominal lesions prior to the
initiation of tuberculostatic therapy.
Chest radiography and thoracic computed tomography (CT) scans revealed small intrapulmonary lesions disseminated in both lungs. Mediastinal lymph
nodes were demonstrated, indicating previous tuberculosis. Over the next 2 weeks, the cutaneous lesions
extended further and revealed liquefaction. Incision
revealed purulent fluid, and antibiotic treatment with
flucloxacillin and ceftriaxone was started.
Histologic studies of the lesions demonstrated
epithelioid giant cell panniculitis. The pus remained
sterile, and the lesions showed ulceration and liquefaction (Figure 1). Acid-fast bacilli were demonstrated in
smears and were found, by polymerase chain reaction, to
be M tuberculosis (for detailed methods, see ref. 8); this
was confirmed thereafter by mycobacterial cultures. In
addition, acid-fast bacilli were demonstrated in gastric
secretions; these were also identified as M tuberculosis.
Urine and stool cultures for mycobacteria yielded negative results. Abdominal CT scans revealed subcutaneous fistulae and a pancreatic tumor suspected to be of
tuberculous origin (Figure 2).
The patient was treated with a 4-fold combination of ethambutol, isoniazid, and rifampin for 3 months
plus streptomycin up to a cumulative dose of 60 gm,
followed by isoniacid/rifampin double therapy for another 6 months. Four months after the initiation of
therapy the cutaneous lesions had healed (Figure 3) and
findings of histologic examination as well as mycobacterial cultures were negative.
Figure 2. Abdominal computed tomography scan, demonstrating a tumor of the pancreatic cauda as well as 1
subcutaneous lesion.
sis, e.g., tertiary syphilis, infection by Sporothrix
schenckii, actinomycosis, and atypical mycobacteriosis,
must be excluded (11-13). Patients should be thoroughly
examined for unusual forms of tuberculous reactivation,
and the patient's immunocompromised state should be
taken into account when deciding on the therapeutic
regimen ( 1 4 3 ) . Initial treatment should consist of a
4-fold combination which includes isoniazid and streptomycin given for at least 2 months, followed by a 3-fold
combination for another 4 months or a 2-fold combination for another 7 months after initiation of therapy.
Moreover, discontinuation or reduction of immunosuppressive therapy is highly recommended (15).
Figure 3. Scrofuloderma 4 months after the initiation of therapy.
This report demonstrates the risk of immunosuppressive therapy in older patients, with respect to the
reappearance of infectious disease believed to be already resolved. In our patient, an encapsulated tuberculous disease was evidently reactivated by the application
of therapeutic doses of steroids over 6 years, partly in
combination with cytostatic agents. In addition to
immunosuppression by antirheumatic drugs, the patient
also had steroid-induced diabetes mellitus and was elderly. These factors led to a reactivation of tuberculous
disease with the development of pulmonary and miliary
tuberculosis. Notably, the patient had never had complaints of pulmonary symptoms. She developed the
tuberculosis subcutana et fistulosa type of tuberculosis
cutis colliquativa. The disease was most likely a result of
miliary distribution and did not develop per continuum,
although pancreatic tuberculosis might conceivably lead
to fistula into the subcutis (9). However, there was no
lymph node involvement, and dermal tuberculosis of the
right thigh occurred simultaneously.
Scrofuloderma caused by hematogenous dissemination has become extremely rare in the last decades
(4,lO). There are only a few reports of this disease to
date and, to our knowledge, this is the first reported case
with multiple lesions (up to 3 cm in diameter) at more
than one site, with subcutaneous fistulae between the
lesions. The emergence of such uncommon forms of
tuberculous disease and the risk of their unexpected and
uncontrolled spread must be considered when prescribing immunosuppressive therapy to high-risk patients.
Other rare diseases included in the differential diagno-
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tuberculosis, terms, colliquativa, long, immunosuppressive, arthritis, cutis, therapy, rheumatoid
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