A Case of Mycobacterial Skin Disease Caused by Mycobacterium peregrinum, and a Review of Cutaneous Infection

An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment

Histopathological features of hind footpads.

A-B) Untreated control mouse at day 33 post-infection. A) Erosion, edema, and fibrinous exudates are observed (H&E x290). B) Aggregated acid-fast bacilli are observed primarily in the stroma, with some present in monocytes (arrowhead) (Fite-Faraco Staining x1750). C) Rifalazil (5mg/kg)-treated mouse at one-week of treatment. Some bacterial cells are fragmented (arrowheads) (Fite-Faraco staining x1750). D-E) Rifalazil (5mg/kg)-treated mouse at 15-weeks of treatment. D) Epithelioid cell granuloma with mild infiltration of lymphocytes is noted. Epidermal erosion, edema, fibrin, and neutrophil aggregation are not observed (H&E x120). E) Granularly degenerated acid-fast bacilli are observed in monocytes (arrowheads) (Fite-Faraco staining x1750). F-G) Rifalazil (5mg/kg)-treated mouse 15 weeks following termination of treatment. F) Epithelioid cell granuloma with mild infiltration of lymphocytes is noted. Epidermal erosion, edema, fibrin, and neutrophil aggregation are not observed (H&E x290). G) Completely degenerated acid-fast bacilli are observed in an epithelioid cell granuloma (Fite-Faraco staining x1750).</p

Workflow of Harmony software image analysis for intracellular <i>M</i>. <i>ulcerans</i>.

THP-1 cell cytoplasm, nuclei, and bacterial immunostaining input image were shown in Fig 4A. Cytoplasm with nucleus were detected by HCS Cell Mask Deep Red and Hoechst 33258 channel respectively (Fig 4B). Bacterial cells were identified as Alexa 488-staining objects within cytoplasm were specifically detected, and calculated the intensity of them (Fig 4C).</p

Gross skin reddening of hind footpads in untreated and rifalazil-treated <i>M</i>. <i>ulcerans</i> infected mice.

Gross skin reddening of hind footpads in untreated and rifalazil-treated M. ulcerans infected mice.</p

Successive measurement of hind footpad thickness.

Measurements were started 33 days post-infection. † All of the mice in the untreated group reached to the endpoint at 4 weeks after the measurement was started.</p

Thickness of hind footpads in <i>M</i>. <i>ulcerans</i> infected mice treated with or without RLZ.

Average of thickness of hind footpads (mean±SD, x10-2 mm). Parentheses indicate the number of mice tested. (XLSX)</p

Log CFU numbers in the hind footpads.

† All of the mice in the untreated group reached to the endpoint at 4 weeks after the measurement was started. N.D Colony was not detected.</p

Gross skin erosion of hind footpads in untreated and rifalazil-treated <i>M</i>. <i>ulcerans</i> infected mice.

Gross skin erosion of hind footpads in untreated and rifalazil-treated M. ulcerans infected mice.</p

Comparative rifamycin efficacy against intracellular <i>M</i>. <i>ulcerans</i> with THP-1 human macrophage infection model.

The sum of fluorescence intensity (Alexa Flour 488) of intracellular bacterium after 72 hours incubation with RFP10μg/mL, RFP10μg/mL+SM10μg/mL, RLZ 10μg/mL and RLZ 10μg/mL+SM10μg/mL. Data are shown as mean ±SD. *p< 0.05 by unpaired t-test.</p