Unusual Cutaneous Manifestations of Miliary Tuberculosis

Abstract

Cutaneous manifestations of miliary tuberculosis are extremely rare. We describe a 62-year-old woman with leukopenia who developed infiltrated dermal-hypodermal and ulcerative cutaneous lesions during the course of miliary tuberculosis. Miliary tuberculosis was diagnosed when Mycobacterium tuberculosis bacilli were isolated by cultures of the bronchoalveolar lavage fluid and blood and when acid-fast bacilli were detected on histopathologic examination of hepatic, pulmonary, and cutaneous biopsy specimens. With the increasing incidence of immunocompromised patients, unusual presentations of tuberculosis may be observed more often. Acute miliary tuberculosis of the skin is an exceptional manifestation that is due to acute hematogenous dissemination of M. tuberculosis to the skin. We describe a patient who had unusual cutaneous manifestations of miliary tuberculosis.

Tuberculosis is endemic in developing countries and is re-emerging in the industrialized world [1]. In some instances, Mycobacterium tuberculosis may be highly transmissible and virulent [2, 3]. With the increasing incidence of immunocompromised patients, unusual presentations of tuberculosis may be observed more often. One of these unusual manifestations, acute miliary tuberculosis of the skin, is caused by acute hematogenous dissemination of M. tuberculosis to the skin. In their review in 1968, Schermer et al. [4] described 15 cases reported in adults and provided a thorough description of this entity. Here we describe a 62-year-old woman who had miliary tuberculosis with unusual cutaneous manifestations.

Case Report

A 62-year-old woman presented with a fever of 2 weeks' duration and multiple skin lesions. Seven years earlier, she had been treated for a breast adenocarcinoma with surgery, radio-therapy, and chemotherapy. She had no known contact with tuberculosis and no past history of the disease. She was in good health until 1993, when she began new cycles of chemotherapy with anthracycline for suspected metastases. In June 1995, the chemotherapy was discontinued because of leukopenia.

On 30 August, that same year, she was admitted to our department because of persistent fever, despite several courses of antibiotic therapy. On admission, she was dyspneic and her vital signs were as follows: temperature, 39°C; blood pressure, 150/70 mm Hg; pulse, 85/min; and respirations, 20/min. On physical examination, the patient had 10 large, painful skin lesions located on her abdomen, chest, and upper and lower extremities. These lesions were erythematous, violaceous, infiltrated, dermal-hypodermal plaques (diameter, 20–60 mm; figure 1); 1 lesion located on a finger was ulcerated (figure 2). Laboratory studies revealed the following values: WBCs, 1200/mm³ (50% segmented neutrophils); hemoglobin, 8.8 g/L; hematocrit, 27%; platelets, 60,000/mm³. Arterial blood gas parameters determined in room air were as follows: Pco₂, 29.9 mm Hg; Po₂, 44.3 mm Hg; and pH, 7.5. The following were the results of liver function tests: aspartate aminotransferase level, 130 U/L (normal range, 7–45 U/L); alanine aminotransferase level, 55 U/L (normal range, 7–56 U/L); alkaline phosphatase level, 206 U/L (normal range, 36–120 U/L), and conjugated bilirubin level, 32.2 µM/L (normal range, 0–2 µM/L). Her HIV serology was negative.

Therapy for presumed gram-negative bacilli septicemia was started with ceftazidime and tobramycine associated with granulocyte colony-stimulating factor. However, both radiographic examination and CT scan of the chest showed diffuse reticulonodular infiltrates of both lungs, typical of miliary tuberculosis. Because the patient remained febrile, antituberculous therapy with isoniazid, rifampin, pyrazinamide, and ethambutol were added to the treatment regimen.

Evaluation of the skin biopsy specimen revealed multiple necrotic lesions at the border between the dermis and the subcutaneous tissue, confirming the diagnosis of tuberculosis. These were not true granulomas, since they were composed of hydropic and dead macrophages. Ziehl-Neelsen staining showed many extracellular acid-fast bacilli within the areas of necrotic tissue. Some intracellular bacilli were seen in histiocytic cells. Serial sections did not reveal vascular thrombi or intravascular mass or bacilli. Evaluation of hepatic and pulmonary biopsy specimens showed the same features. Bone marrow biopsy showed metastasis of mammary adenocarcinoma and myeloid hypoplasia, but no granuloma or acid-fast bacilli.

The patient was transferred to the intensive care unit. Her condition deteriorated rapidly, and she died 8 days later. Cultures of the bronchoalveolar lavage fluid and blood yielded a strain of M. tuberculosis that was susceptible to all antituberculous agents.

Discussion

This patient had miliary tuberculosis with cutaneous dissemination. Miliary tuberculosis usually develops after hemato-genous dissemination in immunocompromised patients. Disseminated tuberculosis has been reported in association with cancers, in some cases after chemotherapy or therapy with glucocorticoids [5]. Our patient had not received glucocorticoids, but she was leukopenic. Severe hematologic abnormalities, such as leukopenia and pancytopenia, have been reported as complications of disseminated tuberculosis after bone marrow invasion by mycobacteria [6–8]. However, the leukopenia seen in our patient was probably a result of the medullar infiltration by metastatic adenocarcinoma.

Our patient had unusual cutaneous manifestations. Cutaneous lesions associated with miliary tuberculosis have been described as acute miliary tuberculosis of the skin (tuberculosis cutis miliaris disseminata, tuberculosis cutis acuta generalisata, and disseminated tuberculosis of the skin) [4]. Cutaneous tuberculosis may take various forms; lupus vulgaris is the most common type in Europe [9]. However, acute miliary tuberculosis of the skin, a rare manifestation of infection with M. tuberculosis, is due to the hematogenous spread of the bacilli during the course of miliary tuberculosis [4]. This entity, described in children before antituberculous agents were available, is reemerging in immunocompromised adult patients. In their review published in 1968, Schermer et al. [4] described a total of 15 such cases in adult patients. Since then, 22 documented cases have been reported, mainly in the last 8 years [10–24]. Most of them were patients with AIDS [14–24]. Daikos et al. [24] reported that acute miliary tuberculosis of the skin occurred in severely immunocompromised HIV-infected patients with CD4 T cell counts <100/mm³, in some cases with multidrug-resistant tubercle bacilli.

The lesions of acute miliary tuberculosis of the skin have been described as vesiculopapules that become necrotic. Schermer et al. [4] reported bluish-red to brown papules, initially discrete, the size of a pinhead (2–3 mm in diameter), and few in number; the lesions may become capped by tiny vesicles or contain purulent material, and after rupturing, leave papules with a central crust. Macular, pustular, or purpuric lesions, follicular papules, ulcerations, and subcutaneous nodules have occasionally been reported in association with the typical papules [4, 18, 24]. However, in this case both clinical and histological features were uncommon. The patient had unusual, large, inflammatory infiltrated dermal-hypodermal plaques, 1 of which was ulcerated. Such features, which simulate gram-negative bacilli septic emboli in a septic patient with leukopenia, differ from classical and recent descriptions of cutaneous miliary tuberculosis [4, 20, 24]. The classical histological features of acute miliary tuberculosis of the skin consist of areas of an inflammatory infiltrate composed of lymphocytes, plasma cells, and neutrophils with focal superficial dermal areas of necrosis and abscess formation without true caseating granuloma. The presence of acid-fast bacilli with vascular thrombi is characteristic of these lesions [4, 25]. An atypical histological feature was evident in our case, with extensive areas of necrosis without true histiocytic rim or fibrinoid vasculitis.

To our knowledge, there have been no cases of cutaneous miliary tuberculosis with such clinical features reported since those described in the review by Schermer et al. in 1968 [4]. Skin involvement is unusual in miliary tuberculosis [26–32]. The main series on miliary tuberculosis generally do not mention cutaneous lesions, and when mentioned they are not precisely described. Acute miliary tuberculosis of the skin must be differentiated from cutaneous lesions preceding miliary tuberculosis, from those related to an underlying focus, or from those occurring after therapy [33]. Acute miliary tuberculosis of the skin has been classified as an acute hematogenous form of cutaneous tuberculosis by McGregor [34] and Beyt [35]. This acute form is characterized by cutaneous lesions occurring during the course of miliary tuberculosis, due to the hematogenous spread of M. tuberculosis bacilli in the skin. Acute miliary tuberculosis of the skin has been associated with a poor prognosis [4]. In the case of our patient, we can suppose that the unusual cutaneous presentation led to a delay in providing effective treatment. This unusual clinical form again illustrates the great diversity within the spectrum of clinical manifestations of tuberculosis and the need to be aware of unusual manifestations of the disease at a time of increasing immunosuppressive conditions.

Acknowledgments

We thank Dr. Jean Philippe Lacour for his helpful criticism; Drs. Jean François Michiels and Marie Christine Saint-Paul for the pathology study; Drs. Véronique Mondain, Francine De Salvador, and Pierre Marie Roger for helping us with the patient's care; and Dr. Boublil for referring to us the patient.

Figures and Tables

Figure 1

Painful erythematous violaceous infiltrated plaques over the lower limbs of a 62-year-old woman with miliary tuberculosis

Figure 2

Acute ulcer of the finger of a 62-year-old woman with miliary tuberculosis