0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Observation |

Blue-Gray Pigmentation in Trunk and Extremities in a 71-Year-Old Man FREE

Mónica Lorente, MD1; Adrián Ballano, MD1; Adriana Juanes, MD1; Maria Antonia Pastor, MD1; Jesús Cuevas, MD2
[+] Author Affiliations
1Department of Dermatology, Hospital Universitario de Guadalajara, Spain
2Department of Pathology, Hospital Universitario de Guadalajara, Spain
JAMA Dermatol. 2013;149(9):1111-1112. doi:10.1001/jamadermatol.2013.4365.
Text Size: A A A
Published online

Fluoroquinolones are a group of antibiotics widely used nowadays. Gastrointestinal and central nervous system symptoms are its most common adverse effects. Skin reactions are infrequent. We report herein a case of blue-gray pigmentation associated with levofloxacin.

REPORT OF A CASE

A 71-year-old man with a history of hypertension, diabetes mellitus, and renal failure was referred to the Dermatology Department for evaluation of long-lasting pruritus that did not respond to antihistamines. Physical examination revealed a blue-gray pigmentation on the back of his hands, the extensor aspect of his forearms, shins, and neck (Figure 1). The patient had undergone internal fixation of a hip fracture 2 earlier. After surgery, the patient complained of fever and pain for several months, but bacterial cultures were performed with negative results. Empirical treatment with rifampicin and levofloxacin was started and continued for 10 months. The patient claimed that the pigmentation began 2 months after he had started this regimen. Drug-induced pigmentation was suspected, and a skin biopsy was performed.

Place holder to copy figure label and caption
Figure 1.
Blue-Gray Pigmentation in Clinical Images

A, Blue-gray pigmentation on the back of the hands and the extensor aspect of the forearms. B, Blue-gray pigmentation affecting the shins. C, Blue-gray pigmentation on the neck.

Graphic Jump Location

Histopathologic examination showed (1) brown, birefringent, hemosiderinlike deposits in macrophages; and (2) myoepithelial cells and fibroblasts in the superficial and deep dermis, hypodermis, and periadnexal structures (Figure 2A). The pigment stained intensely with both Perls (Figure 2B) and Masson-Fontana stains (Figure 2C). Electronic microscopy shoed dense granular deposits inside lysosomes from fibroblasts (Figure 2D). Skin pigmentation associated with levofloxacin was diagnosed, and treatment with the antibiotic was stopped. One year later, the pigmentation remained at lower intensity.

Place holder to copy figure label and caption
Figure 2.
Histopathologic Findings

A, Black-brown deposits in the upper and deep dermis (hematoxylin-eosin, original magnification ×10). B, Panoramic view in which deposits are positively stained in superficial and deep layers (Perls stain, original magnification ×4). C, Interstitial and perivascular deposits positively stained with this argent technique (Masson-Fontana stain, original magnification ×40). D, Deposits corresponding to an exogenous material inside lysosomes of fibroblasts (ultrastructural study).

Graphic Jump Location

DISCUSSION

Levofloxacin is a third-generation quinolone with broad-spectrum antibiotic action against gram-positive and atypical agents. In osteomyelitis and prosthetic infections, levofloxacin in combination with rifampicin is the first-line treatment. Levofloxacin has a good safety profile; gastrointestinal and neurologic symptoms are its most common adverse effects. Skin adverse reactions are rare, and hypersensitivity reactions are the most common presentation.1 Epidermal toxic necrosis syndrome has also been reported. Pigmentation associated with levofloxacin is extremely infrequent, and to our knowledge, only 1 case has been previously reported in the literature,2 in a 68-year-old woman who showed blue-gray pigmentation in both legs after taking levofloxacin for 4 months.

Similar findings have been described in association with other antibiotics, such as pefloxacin3 and minocycline. Minocycline pigmentation is a well-known adverse effect, and 3 clinical forms can be distinguished. In type 1, the pigmentation is confined to scars or sites with previous inflammation or trauma. In type 2, blue-gray pigmentation occurs within previously normal-appearing skin, especially in the lower legs and forearms. Type 3 is characterized by the presence of diffuse brownish discoloration of sun-exposed areas. Histopathologically, types 1 and 2 demonstrate pigment granules in the dermis, concentrated around vasculature within macrophages, and, in type 2, around myoepithelial cells as well. Perls staining is positive in type 1. In type 2, both Perls and Masson-Fontana stainings are positive. In type 3, there is increased melanin in basal keratinocytes with subjacent dermal melanophages without the presence of iron. Only Masson-Fontana staining is positive in this type.4

Ultrastructural observations have confirmed that the clinical coloration is a result of a minocycline derivative chelated with iron that is stored within the lysosomes of macrophages. To our knowledge, there are no reports of cutaneous pigmentation due to rifampicin. Our patient’s symptoms and the histologic findings were similar to those described for minocycline pigmentation type 2 and previous cases associated with levofloxacin and pefloxacin.

The course of the pigmentation is unknown, but it tends to fade if levofloxacin treatment is discontinued. Months or years are necessary to achieve resolution, although in some cases the pigmentation can be permanent. Treatment with Q-switched laser has been reported with successful results.5

ARTICLE INFORMATION

Corresponding Author: Mónica Lorente, MD, Donantes de Sangre s/n, E-19002 Guadalajara, Spain (m.lorente.luna@gmail.com; mlorentel@sescam.jccm.es).

Published Online: July 3, 2013. doi:10.1001/jamadermatol.2013.4365.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Special thanks to Miguel Angel Martínez, MD, Hospital 12 de Octubre, Madrid, for ultrastructural study.

REFERENCES

Liu  HH.  Safety profile of the fluoroquinolones: focus on levofloxacin. Drug Saf. 2010;33(5):353-369.
PubMed   |  Link to Article
López-Pestaña  A, Tuneu  A, Lobo  C, Zubizarreta  J, Eguino  P.  Blue-black pigmentation of legs and arms in a 68-year-old woman. Arch Dermatol. 2007;143(11):1441-1446.
PubMed   |  Link to Article
Le Cleach  L, Chosidow  O, Peytavin  G,  et al.  Blue-black pigmentation of the legs associated with pefloxacin therapy. Arch Dermatol. 1995;131(7):856-857.
PubMed   |  Link to Article
Bowen  AR, McCalmont  TH.  The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836-839.
PubMed   |  Link to Article
Green  D, Friedman  KJ.  Treatment of minocycline-induced cutaneous pigmentation with the Q-switched Alexandrite laser and a review of the literature. J Am Acad Dermatol. 2001;44(2)(suppl):342-347.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Blue-Gray Pigmentation in Clinical Images

A, Blue-gray pigmentation on the back of the hands and the extensor aspect of the forearms. B, Blue-gray pigmentation affecting the shins. C, Blue-gray pigmentation on the neck.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Histopathologic Findings

A, Black-brown deposits in the upper and deep dermis (hematoxylin-eosin, original magnification ×10). B, Panoramic view in which deposits are positively stained in superficial and deep layers (Perls stain, original magnification ×4). C, Interstitial and perivascular deposits positively stained with this argent technique (Masson-Fontana stain, original magnification ×40). D, Deposits corresponding to an exogenous material inside lysosomes of fibroblasts (ultrastructural study).

Graphic Jump Location

Tables

References

Liu  HH.  Safety profile of the fluoroquinolones: focus on levofloxacin. Drug Saf. 2010;33(5):353-369.
PubMed   |  Link to Article
López-Pestaña  A, Tuneu  A, Lobo  C, Zubizarreta  J, Eguino  P.  Blue-black pigmentation of legs and arms in a 68-year-old woman. Arch Dermatol. 2007;143(11):1441-1446.
PubMed   |  Link to Article
Le Cleach  L, Chosidow  O, Peytavin  G,  et al.  Blue-black pigmentation of the legs associated with pefloxacin therapy. Arch Dermatol. 1995;131(7):856-857.
PubMed   |  Link to Article
Bowen  AR, McCalmont  TH.  The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836-839.
PubMed   |  Link to Article
Green  D, Friedman  KJ.  Treatment of minocycline-induced cutaneous pigmentation with the Q-switched Alexandrite laser and a review of the literature. J Am Acad Dermatol. 2001;44(2)(suppl):342-347.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections