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10.2 Hypersensitivity
(xerostomia) and ocular dryness (keratoconjunctivitis), due to autoimmune epithelial destruction
of the salivary and lacrimal glands, respectively. Almost half of the cases only have isolated glandular involvement (primary Sjögren), and the rest are associated with other autoimmune diseases such
as rheumatoid arthritis, lupus erythematosus, etc. (secondary Sjögren)(31). Most patients with
Sjögren syndrome have positive rheumatoid factor, as well as ANAs against SS- A (Ro) and SS- B (La)
ribonucleoproteins(32). The immune mechanism involved in this disease is both cellular and
+
humoral: initiated by CD4
T lymphocytes against a (yet unknown) self- antigen, which would be
produced after an initiating infectious lesion (Epstein– Barr virus, hepatitis C, etc.). The oral clinical
manifestations of Sjögren syndrome are secondary to hyposialia: oral ulcerations, dysphagia, dental
caries, periodontal disease, lingual atrophy and even candidiasis(33) (Figure 10.3). The diagnosis
requires a biopsy of the minor salivary glands, in which periductal focal chronic inflammatory aggregates (>50 lymphocytes and plasma cells), acinar atrophy and fibrosis are identified. Sometimes,
this infiltration becomes a proliferative lymphocytic expansion (benign lymphoepithelial lesion)
that may develop into non- Hodgkin B- cell lymphoma(34).
10.2.2.4 T Lymphocyte- Mediated Hypersensitivity (Type IV)
T lymphocyte- mediated hypersensitivity (type IV) is mediated by antigen- specific T cells and
+
includes delayed- type hypersensitivity (CD4
+
cytotoxicity (CD8
Similarly, CD4
T cells)(14).
+
T lymphocyte- mediated inflammatory reaction depends on the cytokine
environment on the one hand, IFN- γ- producing CD4
and, on the other hand, transforming growth factor (TGF)- β- producing CD4
T cells) and cytotoxic T lymphocyte- mediated
+
Th1 T cells induce macrophage responses;
+
Th17 T cells
modulate neutrophilic responses(22).
Granulomatous inflammation is a macrophage response that occurs when persistent antigens,
or those that cannot be degraded, provoke a chronic activation of macrophages. These granulomas
are organised as clusters of epithelioid cells (modified macrophages), sometimes forming multinucleated giant cells, and bordered by lymphocytes. In the oral cavity, non- infectious immune granulomas are infrequent and normally correspond to reactions to foreign bodies (cosmetic or dental
materials, aliments, etc.) or are idiopathic (granulomatous cheilitis)(35).
Erythema multiforme is a typical neutrophilic- based mucocutaneous immunological disease of
uncertain aetiopathogenesis. Up to 50% of cases have a triggering factor (previous herpes simplex
virus infection, antibiotic use, analgesics, anti- inflammatory drugs, etc.) (36). Histopathological
examination reveals the presence of sub- or intra- epithelial vesicles with keratinocyte necrosis,
and a mixed inflammatory infiltrate with lymphocytes, neutrophils and eosinophils(36).
+
T- lymphocyte- mediated cytotoxicity reactions are the predominant immune response to
CD8
viral infections or tumor cells, and even to healthy epithelial cells(14, 22). Oral lichen planus is a
chronic disorder of unknown aetiology and immunological basis, which is caused by a delayed
+
T cell- mediated inflammatory reaction against non- specific antigens present in the keratino-
CD8
cytes of the basal layer(37). This oral potentially malignant disorder is mainly idiopathic and most
141
planusis the asymptomatic white reticular papule (Wickham), generally bilateral and symmetrical, located in the buccal, lingual, gingival or labial mucosa, with or without other lesions
(patches, ulcers, erythema, etc.) (38). This clinical picture must also be differentiated from
lichenoid lesions, which are usually unilateral, asymmetric and secondary to contact with dental
materials, drugs, graft- versus- host disease, etc., or just idiopathic. The histopathological aspect
of these oral disorders is indistinctive, showing different degrees of atrophy and epithelial
hyperkeratosis, along with a chronic band- like inflammatory infiltrate in the lamina propria
t.me/Dr_Mouayyad_AlbtousH
(a)
(b)
142
(c)
(d)
(e)
Figure10.3 (a and b) Sjögren’s syndrome: severe dental and periodontal pathology, lingual atrophy and
erythematous candidiasis, secondary to hyposialia; (c) severe keratoconjunctivitis due to lacrimal leakage;
(d) immunohistochemistry with periductal T- lymphocytic inflammatory foci and acinar destruction (CD3);
(e)development of a benign parotid lymphoepithelial lesion in a patient with Sjögren’s syndrome (H&E).
(predominantly T lymphocytes), which is sometimes associated to areas of basal degeneration and
keratinocyte apoptosis (Civatte bodies). Microscopic findings rely on many factors (activity phase
of the disease, location and type of lesion, etc.), and reveal the different stages of the lichenoid
immune disorder(38, 39). The disorder is initiated by basal keratinocytes that induce an inflam-
+
matory response of cytotoxic CD8
T lymphocytes, which later activate and secrete proinflammatory molecules (TNFα, IFNγ, IL- 1, IL- 6 and IL- 8), leading to keratinocyte death via apoptosis
(Civatte bodies) (Figure 10.4) and release of more inflammatory and growth factors that further
stimulate the inflammatory process to become chronic. In some cases, immunofluorescence demonstrates a linear deposition of fibrinogen in the basement membrane zone(38).
t.me/Dr_Mouayyad_AlbtousH
(a) (b)
(c)
(d)
Dc
CD8+
IL-1
IL-6
IL-8
TNFα
IFNγ
10.3 Summary
CD4+
143
Figure10.4 (a) Patient with oral lichen planus showing linear white papular lesions on the buccal mucosa;
(b) biopsy compatible with oral lichen planus with epithelial hyperkeratosis, atrophy, basal degeneration
and chronic parabasal inflammation in the chorion (H&E); (c) detail of Figure10.4b, revealing an area of
lichenoid degeneration of the basal keratinocytes associated to chronic inflammation and apoptotic bodies
(Civatte) (H&E); (d) schema of oral lichenoid disease immunopathogenesis, from antigenic recognition by
dendritic cells (Dc) to CD8 T- lymphocyte activation, multimolecular production, keratinocyte degeneration
and subsequent inflammatory chronification with CD4
Another example of type IV hypersensitivity occurs in graft- versus- host disease, affecting
patients undergoing stem cell or bone marrow transplantation for different lymphoproliferative
processes (40). This pathology is currently considered an oral potentially malignant disorder
andshows mucocutaneous lesions similar to those of a lichenoid process. In this case, immuno-
+
competent donor CD8
triggering an inflammatory reaction and immunosuppression(38, 40).
T cells recognise host cells as foreign (HLA compatible but not identical),
10.3 Summary
The mechanisms involved in the immune response and host defence are a very important and
complex part of oral pathophysiology. This knowledge is essential for understanding the aetiopathogenesis, clinical expression and therapeutic management of many oral disorders, both infectious
and inflammatory, and even oncogenic.
+
T lymphocytes.
t.me/Dr_Mouayyad_AlbtousH
144
Abbreviations
ANA Antinuclear antibodies
APC Antigen- presenting cells
ASS Anti- Sjögren’s- syndrome- related antigen
Bim Bcl- 2interacting mediator of cell death
C Complement protein
CD Cluster of differentiation
DAMP Danger- associated molecular pattern
DNA Deoxyribonucleic acid
FasL Type- II transmembrane protein ligand
HLA Human leukocyte antigens
IFN Interferon
Ig Immunoglobulin
IL Interleukin
MHC Major histocompatibility complex
MMP Matrix metalloproteinase
NK Natural killer
NLR Nod- like receptor
PAMP Pathogen- associated molecular patterns
PRR Pattern recognition receptor
RANKL Receptor activator for nuclear factor κB ligand
TGF Transforming growth factor
TNF Tumor necrosis factor
TCR T cell receptor
Th T helper type
TLR Toll- like receptor
References
1 Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nature
Immunol. 2014;5(10):971– 4. https://doi.org/10.1038/ni1004- 971.
2 Newton K, Dixit VM. Signalling in innate immunity and inflammation. Cold Spring Harb Perspect
Biol. 2012;4(3):a006049. https://doi.org/10.1101/cshperspect.a006049.
3 Liu J, Cao X. Cellular and molecular regulation of innate inflammatory responses. Cell Mol
Immunol. 2016;13(6):711– 21. https://doi.org/10.1038/cmi.2016.58.
4 Feller L, Altini M, Khammissa RAG, Chandran R, Bouckaert M, Lemmer J. Oral mucosal immunity.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(5):576– 83. https://doi.org/10.1016/j.oooo.
2013.07.013.
5 Xi R, Zheng X, Tizzano M. Role of taste receptors in innate immunity and oral health. J Dental Res.
2022;101(7):759– 68. https://doi.org/10.1177/00220345221077989.
6 Akira S, Misawa T, Satoh T, Saitoh T. Macrophages control innate inflammation. Diabetes Obes
Metab. 2013;15(3):10– 8. https://doi.org/10.1111/dom.12151.
7 Meyle J, Dommisch H, Groeger S, Giacaman RA, Costalonga M, Herzberg M. The innate host
response in caries and periodontitis. J Clin Periodontol. 2017;44(12):1215– 25. https://doi.org/
10.1111/jcpe.12781.
t.me/Dr_Mouayyad_AlbtousH
8 Boehm T, Swann JB. Origin and evolution of adaptive immunity. Annu Rev Anim Biosci.
2014;2:259– 83. https://doi.org/10.1146/annurev- animal- 022513- 114201.
9 Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125(2):S33– 40.
https://doi.org/10.1016/j.jaci.2009.09.017.
10 Cronkite DA, Strutt TM. The regulation of inflammation by innate and adaptive lymphocytes.
JImmunol Res. 2018;11:467538. https://doi.org/10.1155/2018/1467538.
11 Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity.
ImmunolRev. 2009;227(1):221– 33. https://doi.org/10.1111/j.1600- 065X.2008.00731.x.
12 Becerra- Ruiz JS, Guerrero- Velázquez C, Martínez- Esquivias F, Martínez- Pérez LA, Guzmán- Flores
JM. Innate and adaptive immunity of periodontal disease. From etiology to alveolar bone loss.
OralDis. 2022;28(6):1441– 7. https://doi.org/10.1111/ODI.13884.
13 Blanco P, Palucka AK, Pascual V, Banchereau J. Dendritic cells and cytokines in human
inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 2008;19(1):41– 52.
https://doi.org/10.1016/j.cytogfr.2007.10.004.
14 Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part II): classifications and
current diagnostic and treatment approaches. Allergo J Int. 2020;29:139– 54. https://doi.org/
10.1007/s40629- 020- 00127- 5.
15 Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern
Med. 2015;278(4):369– 95. https://doi.org/10.1111/joim.12395.
16 Baecher- Allan C, Hafler DA. Human regulatory T cells and their role in autoimmune disease.
Immunol Rev. 2006;212(1):203– 16. https://doi.org/10.1111/j.0105- 2896.2006.00417.x.
17 Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol.
2009;155(1):1– 15. https://doi.org/10.1111/j.1365- 2249.2008.03834.x.
18 Uzzaman A, Cho SH. Classification of hypersensitivity reactions. Allergy Asthma Proc.
2012;33(1):96– 9. https://doi.org/10.2500/aap.2012.33.3561.
19 Farnam K, Chang C, Teuber S, Gershwin ME. Nonallergic drug hypersensitivity reactions.
IntArchAllergy Immunol. 2012;159(4):327– 45. https://doi.org/10.1159/000339690.
20 Axéll T. Hypersensitivity of the oral mucosa: clinics and pathology. Acta Odontol Scand.
2001;59(5):315– 9. https://doi.org/10.1080/000163501750541192.
21 Reinhart JP, Stoopler ET, Crawford GH. Oral hypersensitivity reactions. Dermatol Clin.
2020;38(4):467– 76. https://doi.org/10.1016/j.det.2020.05.007.
22 Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important
differential diagnosis in complex immune- derived adverse events. Allergo J. 2020;29(4):32– 61.
https://doi.org/10.1007/s15007- 020- 2550- 1.
23 Batistella EÂ, Sabino da Silva R, Rivero ERC, Silva CAB. Prevalence of oral mucosal lesions in
patients with pemphigus vulgaris: a systematic review and meta- analysis. J Oral Pathol Med.
2021;50(8):750– 7. https://doi.org/10.1111/jop.13167.
24 Scully C, Challacombe SJ. Pemphigus vulgaris: update on etiopathogenesis, oral manifestations,
and management. Critical Rev Oral Biol Med. 2002;13(5):397– 408. https://doi.org/10.1177/
154411130201300504.
25 Carey B, Setterfield J. Mucous membrane pemphigoid and oral blistering diseases. Clin Exp
Dermatol. 2019;44(7):732– 9. https://doi.org/10.1111/ced.13996.
26 Petruzzi M. Mucous membrane pemphigoid affecting the oral cavity: short review on
etiopathogenesis, diagnosis and treatment. Immunopharmacol Immunotoxicol. 2012;34(3):363– 7.
https://doi.org/10.3109/08923973.2011.608684.
27 Zeng Q, Liu J, Mu J, Yang J, Gao Q, Wu F, etal. Optimal biopsy site for the diagnosis of oral
pemphigus vulgaris and mucous membrane pemphigoid: a systematic review and meta- analysis.
145
t.me/Dr_Mouayyad_AlbtousH
146
Int J Oral Maxillofac Surg. 2023;S0901- 5027(23):00129– 7. https://doi.org/10.1016/j.ijom.
2023.05.005.
28 Caielli S, Wan Z, Pascual V. Systemic lupus erythematosus pathogenesis: interferon and beyond.
Annu Rev Immunol. 2023;41:533– 60. https://doi.org/10.1146/annurev- immunol- 101921- 042422.
29 Wenzel J. Cutaneous lupus erythematosus: new insights into pathogenesis and therapeutic
strategies. Nat Rev Rheumatol. 2019;15(9):519– 32. https://doi.org/10.1038/s41584- 019- 0272- 0.
30 Menzies S, O’Shea F, Galvin S, Wynne B. Oral manifestations of lupus. Ir J Med Sci.
2018;187(1):91– 3. https://doi.org/10.1007/s11845- 017- 1622- z.
31 Vivino FB, Bunya VY, Massaro- Giordano G, Johr CR, Giattino SL, etal. Sjogren’s syndrome: an
update on disease pathogenesis, clinical manifestations and treatment. Clin Immunol.
2019;203:81– 121. https://doi.org/10.1016/j.clim.2019.04.009.
32 Zhan Q, Zhang J, Lin Y, Chen W, Fan X, Zhang D. Pathogenesis and treatment of Sjogren’s
syndrome: review and update. Front Immunol. 2013;14:1127417. https://doi.org/10.3389/
fimmu.2023.1127417.
33 Ngo DYJ, Thomson WM. An update on the lived experience of dry mouth in Sjögren’s syndrome
patients. Front Oral Health. 2021;2:767568. https://doi.org/10.3389/froh.2021.767568.
34 Langerman AJ, Blair EA, Sweiss NJ, Taxy JB. Utility of lip biopsy in the diagnosis and treatment
ofSjogren’s syndrome. Laryngoscope. 2007;117(6):1004– 8. https://doi.org/10.1097/MLG.
0b013e31804654f7.
35 Lafuente- Ibáñez de Mendoza I, Vigarios E, Herbault- Barres B, Alberdi- Navarro J, Sibaud V, Maret
D, etal. Non- infectious granulomatous disorders of the upper lip: clinicopathological analysis of
11 patients. BMC Oral Health. 2022;22(1):173. https://doi.org/10.1186/s12903- 022- 02189- z.
36 Celentano A, Tovaru S, Yap T, Adamo D, Aria M, Mignogna MD. Oral erythema multiforme: trends
and clinical findings of a large retrospective European case series. Oral Surg Oral Med Oral Pathol
Oral Radiol. 2015;120(6):707– 16. https://doi.org/10.1016/j.oooo.2015.08.010.
37 El- Howati A, Thornhill MH, Colley HE, Murdoch C. Immune mechanisms in oral lichen planus.
Oral Dis. 2020;29(4):1400– 15. https://doi.org/10.1111/odi.14142.
38 Aguirre- Urizar JM, Alberdi- Navarro J, de Mendoza ILI, Marichalar- Mendia X, Martínez- Revilla B,
Parra- Pérez C, etal. Clinicopathological and prognostic characterization of oral lichenoid disease
and its main subtypes: a series of 384 cases. Med Oral Patol Oral Cir Bucal. 2020;25(4):e554– 62.
https://doi.org/10.4317/medoral.23576.
39 Alberdi- Navarro J, Marichalar- Mendia X, Lartitegui- Sebastián MJ, Gainza- Cirauqui ML,
Echebarria- Goikouria MA, Aguirre- Urizar JM. Histopathological characterization of the oral
lichenoid disease subtypes and the relation with the clinical data. Med Oral Pat Oral Cir Bucal.
2017;22(3):e307– 13. https://doi.org/10.4317/medoral.21730.
40 Margaix- Muñoz M, Bagán JV, Jiménez Y, Sarrión MG, Poveda- Roda R. Graft- versus- host disease
affecting oral cavity. A review. J Clin Exp Dent. 2015;7(1):e138– 45. https://doi.org/10.4317/jced.51975.
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11
Immune Dysfunctions Affecting theOro- Facial Complex
Yeshwant Rawal
Oral and Maxillofacial Pathology, School of Dentistry, Marquette University, Milwaukee, WI, USA
11.1 Introduction
The immune system, including the complement system, provides effective resistance against
foreign material, including infectious agents. Immune surveillance against tumours has also been
effectively employed as immunotherapy to treat neoplasms. The function of the immune system is
sometimes associated with disadvantageous consequences to the host, with rare severe and fatal
results. These reactions are hypersensitivity disorders and result from excessive or inappropriate
responses to antigenic stimuli. Immunodeficiency states leave the host immunocompromised
and susceptible to infections and unchecked aggressive malignant neoplasms. While most
immunodeficiency states are acquired, some arise due to genetic defects. The ability of the immune
system to distinguish between self and non- self- antigens is an integral part of its evolution but is
not absolute. When the immune system reacts against self- antigens, it results in autoimmunity.
Autoimmune diseases affect just about any tissue in the body. Diseases because of immune
dysfunctions such as hypersensitivity, immunodeficiency and autoimmunity often affect the
Oro- facial complex. These dysfunctions may be isolated to the Oro- facial region or part of a more
extensive, complex systemic presentation. Immune dysfunctions affect dental practice as they may
result in anaphylactic reactions to chemicals and prescribed medications, opportunistic infections,
poor wound healing and oral mucosal immune- mediated ulcers and vesiculoerosive diseases. This
chapter briefly discusses mechanisms involved in immune dysfunction and provides essential
information on orofacial diseases of hypersensitivity, immunodeficiency and autoimmunity.
147
11.2 Hypersensitivity Disorders
Hypersensitivity disorders result when the normally helpful immune response becomes inappropriate and exaggerated. The Coombs and Gell classification of hypersensitivity disorders is most
widely accepted. It separates these disorders into four types based on the underlying immune
mechanisms that result in the clinical signs and symptoms. The antigenic stimulus and the type
and extent of the immune response (severity of the disorder) can vary from one person to another
and from one episode to the next.
Pathological Basis of Oral and Maxillofacial Diseases, First Edition. Edited by S. R. Prabhu, Syed Ali Khurram,
OmarKujan and Merva Soluk Tekkesin.
© 2025 John Wiley & Sons Ltd. Published 2025 by John Wiley & Sons Ltd.
t.me/Dr_Mouayyad_AlbtousH
148
11.2.1 Type IHypersensitivity Disorders (Immediate/Anaphylactic)
These are acute and variably severe reactions to an antigenic stimulus (shocking dose) that the
body has become previously sensitised to (sensitising dose). The term anaphylaxis is derived from
the Greek words ana (again) and phylaxis (guarding). Localisation and severity of response
depends on the type of antigen, portal of entry and genetic susceptibility of the individual.
The pathophysiology that results in the clinical spectrum of findings is related to the release of
IgE that stimulates mast cell degranulation and the release of histamine and myriad vasoactive
(dilatation) and bronchial smooth muscle contracting cytokines.
Atopy is a term used to describe type I hypersensitivity disorders against common environmental
antigens such as pollen, mites, other insect bites, fungal spores, milk, eggs, peanuts, etc. Patients
often have a family history of asthma, urticaria, eczema, food allergy and hay fever. The reaction to
the antigens is immediate but highly variable (e.g. peanut allergy may range from mild reactions
to severe life- threatening anaphylaxis). Anaphylactic reactions also occur in those with no
familyhistory.
Common causes of anaphylactic reactions of concern to a dental practitioner include antibiotics
(with penicillin being the most common), non- steroidal anti- inflammatory drugs (NSAIDs), latex,
dyes used in toothpaste, parabens and sulphites in anaesthetic solutions, imaging study contrast
media, resins and other dental compounds.
Signs and symptoms of a severe anaphylactic reaction include a sudden tightness in the throat
with a hoarse voice, swelling of the tongue, lips and face, vomiting, stomach cramps, wheezing,
cough, rhinorrhoea, conjunctivitis, weak pulse, hives, pale or blue skin, dizziness, confusion, low
blood pressure.
Management of type I hypersensitivity disorders depends on the severity of the reaction. Once
recognised, atopy may be prevented by avoiding the known allergen. Desensitisation therapy benefits are temporary at best. Antihistamines and corticosteroids are the mainstay in the management of symptoms. Severe anaphylactic reactions will require administration of 0.5 ml of 1:1000
adrenaline IM up to a maximum of three such doses if needed, antihistamines, corticosteroids and
activation of the emergency protocol while simultaneously providing basic life support measures.
Bronchodilators such as metaproterenol may be required to manage delayed bronchospasms
induced by leucotrienes of slow- reacting substance of anaphylaxis (SRS- A).
11.2.2 Type II Hypersensitivity Disorders (Cytotoxic/Antibody- mediated)
These disorders are selective to cell types and some extracellular matrix antigens. The antibodies
are pathogenetic and belong mainly to the IgG type. If against a cell, the attachment of the antibody with an epitope on the cell triggers a variety of mechanisms, including activation of the
complement pathway with the formation of the membrane attack complex C5b- 9, activation of
effector cells such as macrophages, neutrophils, eosinophils and natural killer (NK) cells by recognition of the Fc receptor of the bound antibody, release of leukotrienes, prostaglandins, chemokines,
fibrin peptides and other chemotactic molecules, opsonisation and opsonin triggered lysosomal
activity and cell- damaging superoxide production.
Classic cell type examples of type II hypersensitivity disorders include erythrocytes in diseases
such as transfusion reactions, haemolytic diseases of the newborn and autoimmune haemolytic
anaemias. Examples of type II hypersensitivity disorders due to pathogenetic antibodies against
extracellular matrix antigens include Goodpasture’s syndrome, myasthenia gravis, Lambert- Eaton
syndrome, pemphigus vulgaris (PV) and pemphigoid.
t.me/Dr_Mouayyad_AlbtousH
Transfusion reactions are a broad category of adverse events related to the transfusion of whole
blood or its components. These include mild hypersensitivity to anaphylactic reactions to foreign
components in donor products, febrile reactions to cytokines released from donor leucocytes, reactions to bacterial contaminants, reactions against heat or osmosis- damaged red cells, graft- versushost disease, etc. Type II hypersensitivity transfusion disorders are related to recipient antibodies
directed against blood donor antigens of the ABO grouping. The recipient antibody is IgM and
results in agglutination of donor erythrocytes, complement activation and intravascular haemolysis. This reaction is acute immediately, and symptoms include fever, hypotension, nausea and vomiting. Other blood groups can induce IgG- linked agglutination of donor erythrocytes and their
destruction in the spleen and liver over several days by developing anaemia, jaundice and renal
tubular necrosis. The incidence of such immunologically mediated type II hypersensitivity transfusion reactions with acute haemolysis is low as blood group typing and matching errors are
mainly nursing and clerical(1).
Haemolytic disease of the newborn occurs when there is a mismatch between the maternal
and foetal red cells, resulting in maternal IgG- induced haemolysis of foetal red cells in utero.
The mismatch most commonly involves the Rhesus D antigen followed by the Kell system K
antigen of the red cells. The first incompatible fetus is unaffected. However, the Rh- mother is
+
sensitised to the first Rh
+
quent Rh
fetus suffers from maternal IgG- induced haemolysis, the effects of which may
fetus and produces IgG antibodies against this Rh+ antigen. A subse-
extend from anaemia to hydrops foetalis with hyperbilirubinemia and kernicterus in the newborn. Typing and recognising the maternal and foetal antigens and administering Rh- D IgG
immunoprophylaxis at 28 weeks of gestation, postpartum and during mismatched foetalmaternal haemorrhage events is the best deterrent against haemolytic events in the fetus and
newborn(2).
Autoimmune haemolytic anaemias are a result of autoantibodies against red cell surface antigens. Three primary types are recognised based on the nature of the autoantibodies formed.
Warm autoimmune haemolytic anaemias result when polyclonal IgG and IgM class antibodies
have the highest affinity to Rhesus system antigens at 37 °C. The opsonised erythrocytes are broken
down in the spleen. 50% of cases have no underlying disorder, while others are secondary to or may
even precede leucocytic conditions such as lymphocytic leukaemia, common variable immunodeficiency (CVID) and systemic lupus erythematosus (SLE)(3).
Cold- reactive antibodies are primarily of the IgM class, are monoclonal and fix complement at a
temperature ranging from 0 to 4 °C but can also react up to 30 °C. Patients are older and have clonal
lymphoproliferative bone marrow disorder. The antigen is a precursor molecule of the ABO system
on a red cell membrane. The red cell agglutination takes place during winter in the peripheral
circulation. Clinical features include acrocyanosis, Raynaud- like changes and tissue necrosis(3).
Drug- induced haemolytic anaemias happen when a drug or its metabolite binds to a red cell, and
antibodies are produced against this formed neoantigen. Alternatively, a drug- antibody complex
may attach to a red cell surface with resultant complement- mediated lysis. Thirdly, a drug may
induce an allergic reaction, and the consequent antibodies may be directed against the red cells.
Drugs commonly implicated in such haemolytic anaemias include penicillin, quinine, α- methyldopa,
cephalosporins, piperacillin, NSAIDs, chlorambucil, fludarabine, bendamustine, PD- 1inhibitors
and sulphonamides(3).
Other rarer forms of autoimmune haemolytic anaemias include secondary cold agglutinin
syndrome, paroxysmal cold haemoglobinuria and mixed autoimmune haemolytic anaemias.
Goodpasture’s syndrome results when IgG autoantibody is directed against the renal glomerular
basement membrane, resulting in necrosis and fibrin deposition. The lung alveolar basement
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t.me/Dr_Mouayyad_AlbtousH
150
membrane may also be affected. Tissue destruction is complement- mediated. Younger patients
present with haemoptysis, while older patients develop glomerulonephritis and renal failure.
Antibodies against acetylcholine receptors on muscle membranes prevent acetylcholinetriggered muscle contraction. This condition is known as myasthenia gravis. This results in
progressive muscle weakness. The antibodies demonstrated are of the IgG class. Post- synaptic
complement proteins have also been shown.
Antibody- mediated reactions against tissue antigens resulting in skin conditions such as
pemphigus and pemphigoid will be discussed later, with other autoimmune erosive and vesiculobullous disorders.
11.2.3 Type III Hypersensitivity Disorders (Immune Complex Diseases)
Immune complexes are formed each time an antibody reacts with an antigen. These complexes are
made soluble by complement and removed by the macrophages effectively.
A low- grade persistent infection combined with a weak antibody response, continued production of autoantibody against self- antigen and repeated exposure to inhaled low- grade antigens may
result in the persistence of immune complexes. The immune complexes are circulating in persistent infections such as leprosy and viral hepatitis and in autoimmune diseases such as rheumatoid
arthritis and SLE. Deposition of these circulating complexes in different tissues results in the multisystem manifestations of these diseases. Localised persistence of immune complexes due to
repeated exposure to inhaled low- grade antigens is seen in conditions such as farmers’ lungs.
11.2.3.1 Rheumatoid Arthritis
Rheumatoid arthritis affects the joints of the hands, elbows, shoulders, feet, spine, knee and the
temporomandibular joint with resultant pain, swelling, stiffness and loss of function. Patients may
also experience a fever with fatigue and loss of appetite. Organs and tissues like the heart, lungs,
eyes, blood and skin may also be affected. Symptoms may vary from person to person. There is no
single test to diagnose rheumatoid arthritis. Diagnosis results from findings from medical history,
physical exam, imaging studies and laboratory tests, including rheumatoid factor, anti- cyclic
citrullinated peptide antibody, ESR, C- reactive protein and complete blood count. Management
strategies include symptomatic relief, physical therapy, surgery and medications such as antiinflammatory drugs, corticosteroids, Janus kinase inhibitors and biological agents such as diseasemodifying anti- rheumatic drugs.
11.2.3.2 Systemic Lupus Erythematosus (SLE)
SLE affects multiple organs, including the skin, mucous membranes, joints, kidneys, cardiovascular
system and the central nervous system. The disease results from autoantibodies against nucleic
acids, their binding proteins, and the effects of immune system mediators like type I interferon
(IFN- I). Socioeconomic, genetic and epigenetic factors have also been implicated in the development of the disease. Early symptoms include fatigue, malaise, fever, loss of appetite and weight loss.
Joint and muscle pain and weakness are also felt. Patients develop a macular rash that extends over
the nose from one cheek to the other, producing the characteristic ‘butterfly rash’ that appears to
become pronounced on exposure to sunlight. Other skin lesions include calcinosis cutis, vasculitis
with petechiae formation, alopecia and ulcers. Lesions of the oral and nasal mucosa are ulcerative
and resemble erosive lichen planus (LP). Diffuse desquamative lesions of the gingiva as in erosive
lichen planus are, however, not seen (Figures 11.1– 11.4). Pulmonary disease includes pleuritis,
pneumonitis, pulmonary haemorrhage and emboli. Cardiac involvement results in pericarditis,
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