Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
87 (
6
); 816-818
doi:
10.4103/ijdvl.IJDVL_543_19
pmid:
32056979

Granulomatous reaction following bacillus Calmette–Guérin vaccination: Successful response to clarithromycin

As’ad Al-Hamad Dermatology Center, Kuwait

Corresponding author: Dr. Arti Nanda, P.O. Box: 6759, Salmiya 22078, Kuwait. artinanda@hotmail.com

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Nanda A, Al-Sabah H, Al-Sumait A, AlNaqi N, Al-Otaibi M, AlLafi A. Granulomatous reaction following bacillus Calmette–Guérin vaccination: Successful response to clarithromycin. Indian J Dermatol Venereol Leprol 2021;87:816-8.

Abstract

We report a 3-year-old girl with a delayed nontuberculous granulomatous reaction on a bacillus Calmette–Guérin injection site with dissemination to distant sites who showed a favorable response to clarithromycin used for 12 weeks with no recurrence on a follow-up of more than 2 years.

Keywords

Bacillus Calmette–Guérin vaccination
clarithromycin
granuloma

Introduction

Bacillus Calmette–Guérin vaccine is an attenuated strain of Mycobacterium bovis (M. bovis) widely used as a preventive strategy against tuberculosis. Local adverse reactions at the site of bacillus Calmette–Guérin vaccination have been estimated to occur in 0.1 to 0.5 per 1000 vaccines.1 Disseminated bacillus Calmette–Guérin infection is rare and usually reported in patients with underlying immunodeficiency state.2 Among dermatological complications, both specific and nonspecific complications have been reported.3 The nonspecific complications include erythema, swelling, erosions or ulceration, abscess formation, hypertrophic scarring and keloids. Specific complications include lupus vulgaris, tuberculides, Koch phenomenon-like reaction, local subcutaneous abscess and scrofuloderma.3,4 Rarely, there have been reports of nontuberculous granulomatous reactions.5-8

Whereas the patients with tuberculous granulomatous reactions including lupus vulgaris and scrofuloderma are treated with antitubercular therapy, there is no consensus about the treatment of nontuberculous granulomatous reactions. We report a patient with delayed nontuberculous granulomatous reaction following bacillus Calmette–Guérin vaccination who was treated successfully with clarithromycin.

Case Report

A 3-year-old girl was referred to us with a 3 week history of a rapidly progressive asymptomatic scaly rash on the left arm at the site of bacillus Calmette–Guérin vaccination and three distant lesions on both the legs. She had received a bacillus Calmette–Guérin vaccination at the age of 3 months and was noticed to have a scaly papule at the vaccination site that never healed completely and subsequently extended slowly. The lesions had failed to respond to various topical modalities including antibiotics, mid-potency steroids and moisturizers. There were no associated medical complaints. Her birth history and developmental milestones were reported normal. A family history of tuberculosis was denied. On examination, she was afebrile. Her height and weight were below fifth percentile. She was observed to have large annular erythematous scaly plaque (9 × 10 cm) showing central clearing with mild atrophy and peripheral activity [Figure 1a] on the left arm, one small erythematous scaly plaque about 2 cm in diameter on the left leg [Figure 1b] and two small papules on the right leg. There was no associated lymphadenopathy or hepatosplenomegaly.

Erythematous large plaque showing central clearing with mild atrophy, erosions in the periphery (lower border) and few satellite nodules near the upper border
Figure 1 a:
Erythematous large plaque showing central clearing with mild atrophy, erosions in the periphery (lower border) and few satellite nodules near the upper border
Erythematous plaque on the left leg
Figure 1 b:
Erythematous plaque on the left leg

Skin biopsies for histopathology from the lesion on the left arm and right leg showed similar histological features including marked acanthosis of the epidermis with multiple epithelioid cell granulomas with multiple foreign body multinucleated giant cells surrounded by dense lymphocytic infiltrate in both superficial and deep dermis [Figure 2a and b]. There was no evidence of caseation necrosis. Special stains including periodic acid-Schiff, periodic acid-Schiff-D and Ziehl-Neelsen were negative. Mycobacterial culture and polymerase chain reaction for Mycobacterium tuberculosis on skin biopsy yielded negative results. The Mycobacterium tuberculosis interferon gamma release assay (IGRA) and T-spot tuberculosis test were negative. Her erythrocyte sedimentation rate was 81 mm/h. Various other investigations including complete blood counts, serum biochemistry, liver and renal profile, serum immunoglobulins, T- and B-cell counts and immunophenotyping, chest X ray and ultrasound abdomen and pelvis were reported normal. An evaluation by a pediatric immunologist ruled out any possibility of underlying immunocompromised state including primary immunodeficiency. She was treated with clarithromycin 15 mg/kg/day in two divided doses for 12 weeks with complete clearance [Figure 3]. There was no recurrence on a follow up of two years.

Histopathology of skin biopsy from left-arm showing nodular granulomatous infiltrate of epithelioid cells and multinucleated giant cells surrounded by dense lymphocytic infiltrate (H and E, ×100)
Figure 2 a:
Histopathology of skin biopsy from left-arm showing nodular granulomatous infiltrate of epithelioid cells and multinucleated giant cells surrounded by dense lymphocytic infiltrate (H and E, ×100)
Histopathology of skin biopsy from left-arm showing well-formed epithelioid cell granuloma in the deep dermis (H and E, ×400)
Figure 2 b:
Histopathology of skin biopsy from left-arm showing well-formed epithelioid cell granuloma in the deep dermis (H and E, ×400)
Lesion showing complete healing with some atrophy and dyspigmentation after 3 months of clarithromycin therapy
Figure 3:
Lesion showing complete healing with some atrophy and dyspigmentation after 3 months of clarithromycin therapy

Discussion

Nontuberculous granulomas at bacillus Calmette–Guérin site refer to granulomas that fail to show acid-fast bacilli by special stains, tissue culture or polymerase chain reaction and demonstrate negative relevant blood tests for tuberculosis including interferon-gamma release assay and T-spot tests. The exact pathogenesis of such granulomatous reactions following bacillus Calmette–Guérin vaccination is not certain. It has been proposed that granuloma formation in such patients can be related to a hypersensitivity reaction to the protein content in the vaccination.5,7,8 Chiu et al.6 demonstrated the presence of monosodium glutamate crystals (used as a stabilizer in the bacillus Calmette–Guérin vaccine) in the biopsy specimen from the granuloma and proposed them to be responsible for initiating a foreign body granulomatous reaction in their patient. However, a possibility of the presence of M. bovis strain of low virulence in undetectable amounts in the tissues to be responsible for granulomatous reaction cannot be fully ruled out. Whether there are some other factors that participate in granuloma formation in such cases need to be determined. Because all measures to identify acid-fast bacilli were negative in our patient, he was diagnosed to be having a nontuberculous granulomatous reaction. There is no consensus on treatment of such reactions. Various treatments including topical steroids, curettage and cautery, and antitubercular treatment have been used.5-8 We decided to use systemic therapy due to rapidly progressive large granulomatous lesion on bacillus Calmette– Guérin site, dissemination to distant sites and a prior history of failure to respond to topical steroids used by a primary physician. Clarithromycin monotherapy has previously been reported to be effective in a patient with bacillus Calmette– Guérin-induced regional complications.9 Before considering multidrug therapy with antitubercular treatment for a period of 6 months, we preferred to give a trial with clarithromycin monotherapy and our patient showed a remarkable response. Exact mechanism of action how clarithromycin helps in improving the granulomatous reaction is not clear. In addition to its antimycobacterial susceptibility against M. bovis,10 clarithromycin has also been documented to have antiinflammatory and immunomodulatory effect in patients with cystic fibrosis lung disease.11 Our patient was noticed to have an improvement within 2 weeks of clarithromycin treatment with a complete clearance by the end of 12 weeks.

To conclude, we report a patient with a delayed granulomatous reaction on bacillus Calmette–Guérin vaccination site with dissemination to distant sites who showed a favorable response to clarithromycin. We propose a trial of clarithromycin monotherapy in such patients prior to treatment with conventional multidrug antitubercular treatment is considered.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. , , , , , . BCG complications. Estimates of the risks among vaccinated subjects and statistical analysis of their main characteristics. Adv Tuberc Res. 1984;21:107-93.
    [Google Scholar]
  2. , . Dermatological complications of BCG vaccination. Br J Dermatol. 1963;75:181-92.
    [CrossRef] [Google Scholar]
  3. , , , , , , et al. Disseminated Bacillus Calmette-Guérin infection and immunodeficiency. Emerg Infect Dis. 2007;13:799-801.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , . Disseminated cutaneous eruption after BCG vaccination. Pediatr Dermatol. 1996;13:451-4.
    [CrossRef] [PubMed] [Google Scholar]
  5. . Delayed granulomatous lesion at the Bacillus Calmette-Guérin vaccination site. Acta Derm Venereol. 2001;81:302-4.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , . Foreign body granuloma caused by monosodium glutamate after BCG vaccination. J Am Acad Dermatol. 2006;55:S1-5.
    [CrossRef] [PubMed] [Google Scholar]
  7. , . A lesion at BCG vaccination site. Clin Exp Dermatol. 2009;34:117-8.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , . Granuloma annulare-like reaction to the Bacillus Calmette-Guerin vaccination. Australas J Dermatol. 2013;54:e4-7.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , . Short course of clarithromycin in an immunocompetent patient with BCG-induced regional complications. Dermatol Online J. 2002;8:6.
    [Google Scholar]
  10. , , , , , . Susceptibility pattern of Bacilli Calmette-Guerin strains against pyrazinamide and other major anti-mycobacterial drugs. Arch Pediatr Infect Dis. 2015;3:e17814.
    [CrossRef] [Google Scholar]
  11. , , , , , . Anti-inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease. Mediators Inflamm. 2004;13:111-7.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
3,732

PDF downloads
1,647
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections