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 ......
Clinicopathologic Reports, Case Reports, and Small Case Series |

Minocycline for the Treatment of Ocular and Ocular Adnexal Sarcoidosis FREE

D. J. John Park, MD; John J. Woog, MD; Jose S. Pulido, MD; J. Douglas Cameron, MD
[+] Author Affiliations

Section Editor: W. Richard Green, MD

More Author Information
Arch Ophthalmol. 2007;125(5):705-709. doi:10.1001/archopht.125.5.705.
Text Size: A A A
Published online

Sarcoidosis is a chronic systemic inflammatory disorder characterized by noncaseating granulomas. Although almost any organ can be affected, common sites of involvement include the skin, lungs, lymph node, eye, and ocular adnexa. Corticosteroids have remained the first-line therapy since their introduction in the 1950s.1 However, because of the significant adverse effects associated with chronic corticosteroid use, treatment is typically reserved for those with severe visceral involvement or refractory ocular and ocular adnexal involvement.

A number of steroid-sparing agents have been used with varying success in the treatment of chronic sarcoidosis. Bachelez et al2 reported clinical response in 10 of 12 patients with cutaneous sarcoidosis treated with minocycline. We describe herein the first reported case of ocular, ocular adnexal, and systemic sarcoidosis treated with minocycline.

REPORT OF A CASE

A 41-year-old white woman was referred with a 3-week history of swelling involving the medial canthus, parotid gland, and lacrimal gland area bilaterally. Medical history was positive for morbid obesity, seasonal allergies, depression, spinal stenosis, and psoriasis. Medications included cetirizine, escitaplopram oxalate, furosemide, celecoxib, zaleplon, and allergy shots. Until 8 months prior to our initial examination, the patient was receiving methotrexate for psoriasis. Review of systems was positive for back and joint pain, xerostomia, daytime somnolence, and snoring.

On examination, visual acuity was 20/20 OU and visual fields were full to confrontation. Pupils were equal and reactive with no relative afferent pupillary defect and extraocular movements were full in both eyes. External examination disclosed mildly tender, indurated nodular fullness involving the subcutaneous tissues of the medial canthus and in the lacrimal gland bilaterally (Figure 1A and B). Conjunctival nodules were present (Figure 2A). Posterior segment examination was unremarkable.

Place holder to copy figure label and caption
Figure 1.

External clinical photographs demonstrate fullness of the lacrimal gland and medial canthal area preoperatively (A and B) with resolution 10 months after initiation of minocycline therapy (C and D).

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

Slitlamp biomicroscopic photographs disclose numerous conjunctival nodules (A) with resolution and secondary hyperpigmentation 10 months following initiation of minocycline therapy (B).

Graphic Jump Location

Computed tomographic scan of the orbit disclosed symmetric bilateral enlargement of the lacrimal and parotid glands (Figure 3A). Angiotensin converting enzyme level was 49 U/L (normal, <46 U/L).

Place holder to copy figure label and caption
Figure 3.

Postcontrast computed tomographic scans show enlargement of both lacrimal glands and increased density in the right medial canthal soft tissue (A), a pulmonary nodule in right middle lobe (B), and a radiolucent cyst in the hilum of the right kidney (C).

Graphic Jump Location

Incisional biopsy of the right lacrimal gland and subcutaneous medial canthal masses and fine-needle aspiration biopsy of the parotid gland revealed noncaseating granulomas consistent with sarcoidosis (Figure 4A and B). Gomori methenamine-silver stain for fungi and auramine/rhodamine stain mycobacteria were negative.

Place holder to copy figure label and caption
Figure 4.

Surgical photograph demonstrates an enlarged and inflamed lacrimal gland (A). Light photomicrographs demonstrate lacrimal gland infiltrated with noncaseating granulomas and obliteration of the glandular architecture (B) (original magnification ×400, hematoxylin-eosin), noncaseating granulomas in the kidney (C) (original magnification ×200, hematoxylin-eosin), and skin lesion (D) (original magnification ×40, hematoxylin-eosin).

Graphic Jump Location

Pulmonary evaluation, including polysomnography, revealed obstructive sleep apnea. Computed tomographic scan of the lungs showed patchy infiltrates at both lung bases but no apparent hilar adenopathy; these findings were not considered typical for pulmonary sarcoidosis. A right renal lesion was noted on an abdominal computed tomographic scan (Figure 3C), and excisional biopsy disclosed features consistent with sarcoidosis (Figure 4C). Prednisone therapy was considered at this time but was deferred in view of concern regarding adverse effects given the patient's medical comorbidities.

Two weeks following initial pulmonary evaluation, the patient visited the emergency department with acute dyspnea, new subcutaneous nodules in the chin and perioral area, and worsening papular eruptions on the upper torso (Figure 5A). Chest computed tomographic scan disclosed a new nodule in the middle lobe of the right lung (Figure 3B). Skin biopsy disclosed dermal and pannicular granulomatous inflammation, which was suggestive of sarcoidosis (Figure 4D). Minocycline 100 mg by mouth twice daily was started. Within 3 months, the cutaneous, lacrimal gland, and pulmonary lesions showed marked improvement (Figure 1C and D, Figure 2B, and Figure 4B). Dilated funduscopic examination revealed bilateral choroidal granulomas (Figure 6). Angiotensin converting enzyme level at this time was 89 U/L.

Place holder to copy figure label and caption
Figure 5.

Clinical photographs show an erythematous tender subcutaneous nodule on the anterior torso measuring approximately 1 cm (A) with resolution and secondary hyperpigmentation 6 months after minocycline therapy (B).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 6.

Fundus color photograph of the right eye shows prominent whitish choroidal granulomas (A) with diminution following treatment (B).

Graphic Jump Location

Seven months after the initiation of minocycline, the cutaneous, conjunctival, and choroidal lesions had regressed with normalization of the angiotensin converting enzyme level (25 U/L) and chest x-ray findings. The patient continued to do well while receiving minocycline 11 months after starting treatment.

COMMENT

Given the morbidity associated with long-term corticosteroid use, steroid-sparing agents have been used with increasing frequency in patients with refractory disease or those requiring long-term corticosteroid administration. In an observational study, Bachelez et al2 treated 12 patients with biopsy-proven cutaneous sarcoidosis with minocycline 200 mg daily over a median 12-month period. With a median follow-up of 26 months, the authors noted complete and partial response to treatment in 8 and 2 patients, respectively. The mean time to reach maximal response was 3.2 months. Of the 8 patients who had a complete response, minocycline was able to be withdrawn in 7, 3 of whom experienced recurrent lesions and received further treatment with doxycycline 200 mg daily. Complete remission was maintained for a mean of 15.3 months. Regression of pulmonary infiltrates and mediastinal lymphadenopathy was noted in the 2 patients with concurrent pulmonary involvement.

The anti-inflammatory properties of tetracyclines have been demonstrated by in vitro studies and corroborated by clinical trials. Tetracycline has been shown to suppress neutrophil migration and chemotaxis,3 and minocycline was shown to inhibit T-lymphocyte activation and proliferation.4 Both minocycline and doxycycline have been shown to obviate granuloma formation in vitro.5 In 2 small, double-blind prospective clinical trials of rheumatoid arthritis, minocycline was shown to affect a significant clinical improvement compared with placebo6 and hydroxychloroquine.7 Minocyline has also been demonstrated to have some clinical effectiveness in early diffuse scleroderma.8

The antimicrobial properties of tetracyclines may play a role in its efficacy in treating sarcoidosis. In a study of 15 patients with sarcoidosis, ribosomal RNA fragments of Propionibacterium acnes and Mycobacterium tuberculosis were isolated from the lymph nodes of 12 and 3 patients, respectively.9 In a collaborative multinational follow-up study, ribosomal RNA fragments of either P acnes or P granulosum was detected in 106 of 108 patients (98%).10

The patient in this report demonstrated a complete and recurrence-free response of the lacrimal gland and choroidal lesions as well as parotid granulomas and pulmonary infiltrates after 3 months of minocycline therapy. To date, the patient has tolerated minocycline with minimal adverse reactions limited to hyperpigmentation in the area of the regressed cutaneous lesions. Hyperpigmentation is a well-known adverse effect of minocycline, is thought to be dose-responsive, and resolves with discontinuation of the medicine.11 Other significant systemic adverse reactions include renal toxicity, hepatotoxicity, hemolytic anemia, Stevens-Johnson syndrome, and elevated intracranial pressure. To our knowledge, this case represents the first case of ocular and ocular adnexal sarcoid treated with minocycline.

ARTICLE INFORMATION

Correspondence: Dr Woog, Department of Ophthalmology, Mayo Clinic, Mayo 7 West, 200 First St SW, Rochester, MN 55905 (woog.john@mayo.edu).

Financial Disclosure: None reported.

REFERENCES

Siltzbach  LE Effects of cortisone in sarcoidosis: a study of thirteen patients. Am J Med 1952;12139- 160
PubMed Link to Article
Bachelez  HSenet  PCadranel  JKaoukhov  ADubertret  L The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 2001;13769- 73
PubMed Link to Article
Esterly  NBKoransky  JSFurey  NLTrevisan  M Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984;1201308- 1313
PubMed Link to Article
Kloppenburg  MVerweij  CLMiltenburg  AM  et al.  The influence of tetracyclines on T cell activation. Clin Exp Immunol 1995;102635- 641
PubMed Link to Article
Webster  GFToso  SMHegemann  L Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin: involvement of protein kinase C. Arch Dermatol 1994;130748- 752
PubMed Link to Article
Tilley  BCAlarcon  GSHeyse  SP  et al.  Minocycline in rheumatoid arthritis: a 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med 1995;12281- 89
PubMed Link to Article
O’Dell  JRBlakely  KWMallek  JA  et al.  Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 2001;442235- 2241
PubMed Link to Article
Le  CHMorales  ATrentham  DE Minocycline in early diffuse scleroderma. Lancet 1998;3521755- 1756
PubMed Link to Article
Ishige  IUsui  YTakemura  TEishi  Y Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet 1999;354120- 123
PubMed Link to Article
Eishi  YSuga  MIshige  I  et al.  Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol 2002;40198- 204
PubMed Link to Article
Tanzi  ELHecker  MS Minocycline-induced hyperpigmentation of the tongue. Arch Dermatol 2000;136427- 428
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

External clinical photographs demonstrate fullness of the lacrimal gland and medial canthal area preoperatively (A and B) with resolution 10 months after initiation of minocycline therapy (C and D).

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

Slitlamp biomicroscopic photographs disclose numerous conjunctival nodules (A) with resolution and secondary hyperpigmentation 10 months following initiation of minocycline therapy (B).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Postcontrast computed tomographic scans show enlargement of both lacrimal glands and increased density in the right medial canthal soft tissue (A), a pulmonary nodule in right middle lobe (B), and a radiolucent cyst in the hilum of the right kidney (C).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Surgical photograph demonstrates an enlarged and inflamed lacrimal gland (A). Light photomicrographs demonstrate lacrimal gland infiltrated with noncaseating granulomas and obliteration of the glandular architecture (B) (original magnification ×400, hematoxylin-eosin), noncaseating granulomas in the kidney (C) (original magnification ×200, hematoxylin-eosin), and skin lesion (D) (original magnification ×40, hematoxylin-eosin).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Clinical photographs show an erythematous tender subcutaneous nodule on the anterior torso measuring approximately 1 cm (A) with resolution and secondary hyperpigmentation 6 months after minocycline therapy (B).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 6.

Fundus color photograph of the right eye shows prominent whitish choroidal granulomas (A) with diminution following treatment (B).

Graphic Jump Location

Tables

References

Siltzbach  LE Effects of cortisone in sarcoidosis: a study of thirteen patients. Am J Med 1952;12139- 160
PubMed Link to Article
Bachelez  HSenet  PCadranel  JKaoukhov  ADubertret  L The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 2001;13769- 73
PubMed Link to Article
Esterly  NBKoransky  JSFurey  NLTrevisan  M Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984;1201308- 1313
PubMed Link to Article
Kloppenburg  MVerweij  CLMiltenburg  AM  et al.  The influence of tetracyclines on T cell activation. Clin Exp Immunol 1995;102635- 641
PubMed Link to Article
Webster  GFToso  SMHegemann  L Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin: involvement of protein kinase C. Arch Dermatol 1994;130748- 752
PubMed Link to Article
Tilley  BCAlarcon  GSHeyse  SP  et al.  Minocycline in rheumatoid arthritis: a 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med 1995;12281- 89
PubMed Link to Article
O’Dell  JRBlakely  KWMallek  JA  et al.  Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 2001;442235- 2241
PubMed Link to Article
Le  CHMorales  ATrentham  DE Minocycline in early diffuse scleroderma. Lancet 1998;3521755- 1756
PubMed Link to Article
Ishige  IUsui  YTakemura  TEishi  Y Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet 1999;354120- 123
PubMed Link to Article
Eishi  YSuga  MIshige  I  et al.  Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol 2002;40198- 204
PubMed Link to Article
Tanzi  ELHecker  MS Minocycline-induced hyperpigmentation of the tongue. Arch Dermatol 2000;136427- 428
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.

Multimedia

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

1,221 Views
8 Citations
×

Related Content

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

Articles Related By Topic
Related Collections
PubMed Articles
Jobs