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Primary cutaneous nocardiosis in immunocompetent children

European Journal of Dermatology. Volume 16, Number 4, 406-8, July-August 2006, Clinical report

Summary

Author(s) : Paola Cecilia Stefano, Amada Libertad Noriega, Andrea Laura Kobrin, María Fernanda Conde, Bettina Andrea Cervini, María Teresa Gonzalez, Jorge Alejandro Laffargue, Patricia Santos, Adrián Martín Pierini , Medical Residents and Scholarship Fellows, Dermatology Department, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina, Staff Doctors, Dermatology Service, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina, Microbiology Service. Mycology, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina, Head of the Dermatology Service, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina.

Summary : Primary cutaneous nocardiosis is an infrequent opportunistic infection that mainly affects immunodepressed hosts. We describe two immunocompetent patients who exhibited two clinical forms of cutaneous nocardiosis, a mycetoma from walking barefoot in contaminated water and in the case of the other patient a lymphocutaneous form on the basis of a stabbing-cutting injury. In both cases the tests performed ruled out any immunodeficiency, particularly chronic granulomatose disease, since nocardiosis is regarded as an infection that acts as a marker for that illness. Treatment with cotrimoxazole led to the total healing of the lesions in both patients.

Keywords : children, immune system, immunodepressed hosts, lymphocutaneous nocardiosis, mycetoma, primary cutaneous nocardiosis

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ARTICLE

Auteur(s) : Paola Cecilia Stefano Paola Cecilia Stefano¹, Amada Libertad Noriega¹, Andrea Laura Kobrin¹, María Fernanda Conde¹, Bettina Andrea Cervini², María Teresa Gonzalez², Jorge Alejandro Laffargue², Patricia Santos³, Adrián Martín Pierini⁴

¹Medical Residents and Scholarship Fellows, Dermatology Department, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina
²Staff Doctors, Dermatology Service, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina
³Microbiology Service. Mycology, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina
⁴Head of the Dermatology Service, Juan P. Garrahan Pediatric Hospital Buenos Aires, Argentina

accepté le 1 Mars 2006

Primary cutaneous nocardiosis is an infrequent opportunistic infection that generally affects immunodepressed hosts. It is produced by Gram positive bacteria, partially acid and alcohol resistant, of the Nocardia genus, which are saprophytes of the soil, water and organic matter.The disease was described for the first time by Edmond Nocard in 1888 [1]. The species that are most frequently responsible are Nocardia brasilensis and Nocardia asteroides.In most cases, the causal agent enters through inhalation, and hematogenic dissemination may occur toward the liver, brain, kidneys, skin and other organs. Direct cutaneous inoculation, as a result of minor trauma caused by thorns of contaminated plants, is less frequent [2].In the patients we describe, the onset of primary cutaneous nocardiosis took place in the absence of provable immunodeficiency.

Clinical cases

Case 1

Male patient, 7 years of age, with a record of slight bronchospasms and under treatment for a hyperactivity syndrome, who was brought in because of the presence of nodules in the left latero-cervical region.

Background to the current illness

The illness had begun approximately 7 months prior to the consultation with one sole nodular, painful lesion, with signs of phlogosis, in the left lateral region of the neck, accompanied by fever, after having been injured by the thorn of a plant at his home. Treatment with oral cephalexin over 10 days did not lead to an improvement. New nodules appeared later, one of which ulcerated leaving an atrophic scar in the supraclavicular cavity.

Physical examination

At the time of the physical examination he presented 8 erythemato-violet firm-elastic nodular lesions, distributed along a line following the lymphatic trajectory toward the supraclavicular cavity ( (figure 1) ). These new nodules were not painful. The rest of the skin and general examination were normal.

Complementary tests

Hemoglobin 12,4 g/%, White blood cells 9,500/mm³, Neutrophils 43%, Lymphocytes 46%. Erythrosedimentation 63 mm in 1^st hour.

PPD : negative

HIV serology: not reactive

Reduction of Dihydrorodamine: normal (ruling out chronic granulamotose disease).

Echography of soft parts: hypoechoic superficial nodular image and rounded lesions in the subcutaneous cell tissue compatible with adenopathies.

Histopathological study (Protocol # 04-2621): Acanthoid epidermis. Dermis: mononuclear inflammatory infiltrate constituted by lymphocytes, histiocytes and multinucleated giant cells with amorphous basophilous material within them, which was also found in the interstices. This was interpreted as a reaction to a foreign body. The PAS and Ziehl-Nielssen tinctures showed neither fungi nor bacteria ( (figure 1B) ).

In culture (Sabouraud agar), the material obtained by puncture aspiration with a fine needle developed a chalky white colony of brain-like form (with short aerial hyphae on the surface) at 46 °C compatible with Nocardia spp.. Ziehl Nielsen stain was partially acid- acohol resistent, exacerbated in Lowenstein Jensen media; Kinyoun with H₂SO₄ 1% stain was acid-alcohol resistant. The hydrolysis of casein, tyrosine and xanthine were negative, the production of ureasa was positive, and was resistent to lysozime; confirming the diagnosis of Nocardia asteroides.

Rx of thorax: Normal.

Treatment and evolution

Treatment was carried out with trimethroprim-sulfamethoxazole (10 mg/kg/day in two doses) for only 30 days. The patient suspended treatment and 5 months later returned to the hospital, the total resolution of the lesions being observed.

Case 2

Male patient, 9 years of age, who was brought in for non-painful edema and erythema and ulcerations in the right foot and ankle.

Background to the current illness

The clinical picture had begun approximately 2 years before the examination with fever and a reddish, painful nodule on the inside face of the right foot, which afterwards ulcerated, drained purulent material and healed leaving a scar. A second lesion with similar features appeared later on the back of the same foot, undergoing the same evolution. Treatments with cephalexin did not lead to an improvement. Family background: mother and siblings diabetic.

Physical examination

At the time of the examination several ulcerations were noted in the malleolar region with numerous exit orifices having scabs on their surface ( (figure 1C) ).

Complementary examinations

Histopathological study (Protocol # 95802): the epidermis and the surface and medium dermis did not exhibit alterations. Polymorphous infiltrate was observed in the deep dermis and hypodermis with histiocytes, lymphocytes, plasmocytes, eosinophils and some polymorphonuclear neutrophils immersed in lax and edematous tissue. PAS and Ziehl-Nielssen tinctures revealed no fungi or bacteria.

Culture in a Sabouraud agar medium at 46 °C developed a partially acid and alcohol resistant bacillus compatible with Nocardia spp. The hydrolysis of casein, tyrosine and xanthine were negative, the production of ureasa was positive, and was resistent to lysozime; therefore, confirming the diagnosis of Nocardia asteroides). Ziehl Nielsen and Kinyoun with H₂SO₄ 1% stain were similar to the first case.

The Nitro Blue Tetrazolium test, which was normal, ruled out any chronic granulamotose disease.

Treatment and evolution

Treatment was carried out with trimethroprim sulfamethoxazole (10 mg/kg/day taken by mouth) for 6 months with total resolution of the lesions and without recurrence in later controls.

Discussion

Skin infection with Nocardia is rare, both among children and among adults.

The most frequent cutaneous occurrence is the one secondary to the hematogenic dissemination of a pulmonary infection; it is followed in frequency by chronic cutaneous nocardiosis or actinomycetoma, and lastly, by primary cutaneous nocardiosis [3] . This latter may be found as an abscess, cellulite or a lymphocutaneous form called sporothricoid because of its clinical similarity to infection with Sporothrix schenckii.

Lymphocutaneous or sporothricoid nocardiosis has a primary lesion at the point of injury, followed by a lymphangitis and subcutaneous nodular lesions along the course of the lymphatic trajectory [4]. Among published cases, 80% have the background of an infection caused by a piercing wound [5].

The mycetoma are nodules or plaques with multiple fistulas that drain purulent material that contains granules of Nocardia, and are generally located on the limbs or trunk. Clinically they are indistinguishable from the mycetoma produced by other agents [6].

In both clinical forms the onset of the illness is acute with fever and inflammatory lesions and thereafter evolves in a chronic form.

As an opportunistic infection, it is most frequently seen in immunodepressed patients, and is regarded as a marker of chronic granulomatose disease [7].

A case has been published of nocardiosis which affected the central nervous system of an immunocompetent child who years later developed an acquired hypogammaglobulinemia [7].

The culture of the material obtained from pustular or nodular lesions, in a Sabouraud agar medium at 37 °C, over 7 to 10 days, allows the diagnosis of Nocardia through the development of characteristic colonies of chalky white color and brain-like aspect [1, 6, 8].

The treatment of choice is trimethroprim sulfamethoxazole, in doses of 10 mg/kg/day taken by mouth. Other antibiotics employed are minocycline, amikacin, cephalosporines, erythromycin and imipenem [9]. The length of treatment is variable. The minimum time necessary in the sporothricoid forms is of approximately 3 months, although healing has been described at the end of one month of treatment, as with our patient No. 1. Mycetoma require a lengthier treatment, of at least 6 months, and in some cases it is necessary to add a surgical drainage [1, 10].

Conclusion

Primary cutaneous nocardiosis is an infrequent infection that is seen preferentially in patients with congenital or acquired immunological alterations.

As an opportunistic infection, its appearance compels us to carry out a detailed study of the bearer’s immunological condition, although cases like ours have been described in which alterations have not been found.

This infection must be suspected in patients with nodular or ulcerous lesions with torpid evolution, secondary to piercing-cutting trauma, a fact which does not always emerge from the anamnesis because of the chronic character of the evolution, and which do not respond to the customary antibiotic treatments.

References

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