Miliary tuberculosis in a patient with eosinophilic fasciitis.

Abstract: The fibrosing disorders represent a diverse group of uncommon chronic diseases that include systemic sclerosis, eosinophilic fasciitis, eosinophilia-myalgia syndrome, toxic oil syndrome, and localized forms of fibrosis. A rare case of eosinophilic fasciitis is reported. The patient was a 61-year-old female who presented with generalized massive edema and eosinophilia. Signs of common edema-producing diseases, such as heart failure, were absent. Corticosteroids were initiated with slow improvement in edema. Over the ensuing months, miliary tuberculosis and tenosynovitis of her left hand and left foot developed, which responded to appropriate treatment. Moreover, prominent induration, hyperpigmentation, and coarse puckering of the skin gradually took place. Other conditions, especially neoplasms and infections, have been described in association with eosinophilic fasciitis, but this is the first reported case of miliary tuberculosis associated with the disease.

Key Words: eosinophilic fasciitis, fibrosing disorders, miliary tuberculosis

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Eosinophilic fasciitis (EF) is a rare condition, characterized by generalized induration of the skin and subcutaneous tissues. (1) Several diseases, especially malignancies (2,3) and some infections, (4) are more prevalent in patients with EF than in the general population. We report a case of miliary tuberculosis in a patient with EF, an association that had not been described before.

Case Report

A 61-year-old female presented with a 4-month history of pitting edema. Initially the process was localized to the lower extremities, but afterward it extended to the whole body, with partial sparing of the face and hands. Her medical history was negative, and she was taking no medications when symptoms began. The physical examination was unremarkable except for generalized massive pitting edema.

Blood analysis showed white blood cells 12,600/[mm.sup.3] (28% eosinophils), hemoglobin 11.2 g/dL, albumin 1.7 g/dL, gamma-globulins 2.1 g/dL, and positive antimicrosomal antibodies. Urinalysis disclosed 25 white blood cells per high power field and 432 mg of proteins per day. Microbiologic studies of serum, urine, and stool were negative. Chest radiographs, an electrocardiogram, and ultrasound studies of the heart, abdomen, and lower extremities were unrevealing. Radiographs of the legs showed subcutaneous edema. A skin biopsy was normal. Prednisone (60 mg per day) was initiated with very slow improvement in edema and eosinophilia.

Six months later, while still taking steroids, she began to have intense pain and stiffness in her left hand, which slowly subsided over several days with administration of anti-inflammatory agents.

One month later, she had intense anorexia, a nonproductive cough, breathlessness, and high fever, with progressive worsening. Chest radiographs showed a tenuous diffuse bilateral infiltrate (Fig. 1), which was more apparent 3 days later (Fig. 2). Blood gas analysis on room air demonstrated partial pressure of oxygen at 67 mm Hg, with a normal pH and partial pressure of C[O.sub.2]. Eye examination was unrevealing. Auramine-rhodamine staining of gastric lavage fluid was positive. All other microbiologic studies of blood, serum, and urine were negative. Isoniazid, rifampin, pyrazinamide, and ethambutol were initiated, with dramatic improvement in symptoms and complete resolution of lung infiltrates over the next 2 weeks. Mycobacterium tuberculosis grew in the gastric fluid specimen.

One week after starting antituberculous treatment, the patient had intense pain and stiffness in her left foot, which slowly resolved with administration of anti-inflammatory agents.

Over the next few months, hyperpigmentation, induration, and irregular coarse puckering of the skin gradually developed, despite continued treatment with prednisone. The proximal lower extremities (Fig. 3) and abdomen were especially affected. A new skin biopsy, carried out 3 years after starting the disease, showed an inflammatory process with perivascular and interstitial infiltrate of lymphocytes and plasma cells, foci of sclerosis at the dermal subcutaneous junction, and thick subcutaneous septa; the epidermis showed no pathologic changes.

Discussion

The fibrosing disorders represent a diverse group of chronic diseases characterized by an excessive accumulation of extracellular matrix components of connective tissue, resulting in dysfunction of affected organs. In addition to systemic sclerosis, the prototype disorder, these conditions include EF, eosinophilia-myalgia syndrome, toxic oil syndrome, and localized forms of fibrosis. (1)

EF is an uncommon disease, with only a few hundred cases reported in the literature so far. The disease is characterized by the acute or subacute symmetric swelling of the skin and subcutaneous tissues. With time, fibrosis ensues, and induration of the same tissues becomes the predominant finding. The forearms, flanks, and upper legs are especially affected, whereas the hands and face are usually spared. Eosinophilia, increased erythrocyte sedimentation rate, and hypergammaglobulinemia are also typical findings in EF. (5)

The underlying cause of EF is unknown, although histologic findings, (6) as well as clinical similarities with toxic oil syndrome (7) and eosinophilia-myalgia syndrome, (8) suggest a possible toxic origin.

Striking pitting edema was the presenting feature in our patient. The symptom was so prominent, that other edemaproducing conditions, such as heart failure, were initially considered in the differential diagnosis. Other cases of EF have presented in a similar manner. (9)

Prognosis of EF is uncertain. Total resolution of clinical signs occurs in some cases, although more commonly some degree of induration remains even after many months of corticosteroid therapy. Our case is remarkable for the severe residual induration, despite the prolonged use of high-dose corticosteroids.

[FIGURE 1 OMITTED]

Several conditions have been described in association with EF, (2-4,10-12) although the pathogenic relation between those disorders and EF is poorly understood.

Miliary tuberculosis is due to hematogenous spread of M tuberculosis. This pattern is seen in 1 to 3% of all tuberculosis cases. The disease is characterized by the widespread seeding of 1 to 5 mm granulomas, which affect the whole organism but are more commonly evidenced in the lungs on chest radiography. Clinical manifestations are nonspecific and protean, with fever, night sweats, weakness, anorexia, and weight loss as presenting symptoms in the majority of cases. Cutaneous manifestations of tuberculosis, including fasciitis, have been described. (14-18) Therefore, a high index of suspicion is required for the diagnosis. (19) If unrecognized, the disease is almost invariably lethal; however, with proper treatment, it is amenable to cure. (13)

[FIGURE 2 OMITTED]

Conclusion

To the best of our knowledge, this is the first report of miliary tuberculosis in a patient with EF. In a search of the database Medline for the years 1966 through 2004, with the query profile ["eosinophilic fasciitis" AND (tuberculosis OR miliary)], we found no other reports of such association. Presumably, corticosteroids favored the development of the infection in our patient. (19)

[FIGURE 3 OMITTED]

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Accepted July 8, 2004.

References

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11. Jacob SE, Lodha R, Cohen JJ, et al. Paraneoplastic eosinophilic fasciitis: a case report. Rheumatol Int 2003;23:262-264.

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13. Hussain SF, Irfan M, Abbasi M, et al. Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country. Int J Tuberc Lung Dis 2004;8:493-499.

14. Del Giudice P, Bernard E, Perrin C, et al. Unusual cutaneous manifestations of miliary tuberculosis. Clin Infect Dis 2000;30:201-204.

15. Rietbroek RC, Dahlmans RP, Smedts F, et al. Tuberculosis cutis miliaris disseminated as a manifestation of miliary tuberculosis: literature review and report of a case of recurrent skin lesions. Rev Infect Dis 1991;13:265-269.

16. Stebbings AE, Ti TY, Tan WC. Necrotizing fasciitis: an unusual presentation of miliary mycobacterium tuberculosis. Singapore Med J 1997;38:383-385.

17. Kabani AM, Yao JD, Jadusingh IH, Lee BC. Tuberculous fasciitis and tenosynovitis: an unusual presentation of miliary tuberculosis. Diagn Microbiol Infect Dis 1993;16:67-71.

18. Lakhanpal S, Linscheid RL, Ferguson RH, Ginsburg WW. Tuberculous fasciitis with tenosynovitis. J Rheumatol 1987;14:621-624.

19. Agrawal PN, Gupta D, Aggarwal AN, Behera D. Incidence of tuberculosis among patients receiving treatment with oral corticosteroids. J Assoc Physicians India 2000;48:881-884.

RELATED ARTICLE: Key Points

* Eosinophilic fasciitis is one of the fibrosing disorders; other diseases of the group include systemic sclerosis, eosinophilia-myalgia syndrome, toxic oil syndrome, and localized forms of fibrosis.

* Miliary tuberculosis is an uncommon modality of tuberculosis, characterized by nonspecific and protean manifestations.

* Several conditions have been described in patients with eosinophilic fasciitis; a case of miliary tuberculosis associated with the disease is reported.

Bernardino Roca, MD, Maria Angeles Bennasar, MD, and Ana Pitarch, MD

From the Department of Medicine, Divisions of Infectious Disease and Dermatology, General Hospital of Castellon, Castellon, Spain.

Reprint requests to Dr. Bernardino Roca, Catalunya, 33-A, 4, 12004 Castellon, Spain. Email: [e-mail]