Tetracycline group


The tetracycline antibiotics are a group of broad spectrum protein synthesis inhibiting compounds used in the treatment of Gram+ and Gram - infections. In dermatological practice, they are commonly used in the treatment of acne and rosacea.
 
Natural tetracyclines: basic tetracycline, chlortetracycline, oxytetracycline
 
Semi-synthetic tetracyclines: doxycycline, minocycline
 
Incidence
Uncommon.
 
Deaths reported.
 
Clinical manifestations
General: anaphylactic shock, serum sickness, fever, arthralgia, arthritis.
 
Respiratory: pneumonitis, bronchospasm.
 
Cutaneous: pruritus, urticaria, erythema multiforme, Lyell’s syndrome, Stevens-Johnson’s syndrome, fixed drug eruption, angioedema, contact dermatitis, photosensitivity.
 
Hepatic: hepatitis.
 
Renal: acute interstitial nephritis.
 
Haematological: autoimmune hemolytic anemia, thrombo-cytopenia, leukopenia.
 
3 distinct syndromes have been reported:
  • hypersensitivity syndrome reaction (HSR): fever, rash, internal organ involvement, occurring 2 to 4 weeks after the start of therapy
     
  • serum sickness like reaction (SSLR): fever, rash, arthralgia and/or lymphadenopathy, urticaria, exanthema
     
  • drug induced lupus (DIL) .
Diagnostic methods
Cutaneous testing.
 
Intradermal skin-tests: positive in one patient with anaphylaxis.
 
Patch-tests (chlortetracycline hydrochloride 0.5% in pet).
 
Hemagglutinating antibodies positive in patients with Lyell’s syndrome .
 
Migration inhibitoryfactor (MIF) + mast cell degranulation test positive in 4/15 patients.
 
Re-challenge with minocycline or tetracycline is not recommended in patients with severe reactions.
 
Mechanisms
The potential reactive metabolites generated by minocycline may bind to tissue macromolecules, thereby causing direct cell damage, or they may act as haptens.
 
Management
Cross-sensitivity between tetracycline/doxycycline and minocycline concerning fixed drug eruptions is not constant.
 
Patients who experienced a serious adverse event while receiving one of the tetracycline antibiotics must avoid all tetracyclines until more information is available.
 
Patients receiving long-term minocycline therapy should have an antinuclear antibody test and assessment of hepatic transaminase levels only if symptoms develop during their course of treatment.

References

  1. Shapiro L.E, Knowles S.R, Shear N.H, "Comparative safety of tetracycline, minocycline and doxycycline", Arch. Dermatol., 1997 ; 133 (10): 1224-30
  2. Knowles S.R, Shapiro L.E, Shear N.H, "Serious adverse reactions induced by minocycline and review of the literature", Arch. Dermatol., 1996 ; 132 (8): 934-9
  3. Harel L, Amir J, Livni E, Straussberg R, Varsano I, "Serum-sickness-like reaction associated with minocycline therapy in adolescents", Ann. Pharmacother., 1996 ; 30: 481-3
  4. Bargman H, "Lack of cross-sensitivity between tetracycline, doxycycline and minocycline with regard to fixed drug sensitivity to tetracycline", J. Am. Acad. Dermatol., 1984 ; 11 (5.1): 900-2
  5. Menon M.P.S, Das A.K, "Tetracycline asthma: a case report", Clin. Allergy., 1977 ; 7: 285-90

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.