Triads in Dermatology

Abstract

It is imperative for any dermatology resident to have a good knowledge of the various triads in dermatology. For an easy grasp over this topic, we have grouped the various triads on the basis of their etiologies.

Introduction

What was known?

A “triad” is a group of three associated entities or objects.

Residents are often quizzed about syndromes and triads during grand rounds which they find difficult to recollect.

Here, we have made an attempt to enlist triads related to clinical dermatology which we hope would be useful for postgraduate students. We have classified them based on the etiologies responsible for them [Table 1].

Table 1.

Triads in dermatology

Infectious

Hutchinson's triad

It represents the stigmata of congenital syphilis characterized by interstitial keratitis, Hutchinson's teeth (peg-shaped, notched permanent incisors), and eighth-nerve deafness.[1,2]

Reiter's syndrome

The classical triad consists of urethritis, acute non-purulent seronegative arthritis, and conjunctivitis. In addition, there may be other distinct mucocutaneous manifestations including circinate balanitis, erosions affecting the buccal and rectal mucosa, and keratoderma blennorrhagica [Figure 1].[3,4]

Figure 1.

(a) Limpet-like scales (b) keratoderma blennorrhagica (c) circinate balanitis in Reiter's syndrome

Mycetoma

Mycetoma may be diagnosed by keeping in mind a triad of signs, namely: tumefaction, sinuses, and granules [Figure 2].[5]

Figure 2.

Multiple nodules with discharge and sinuses in mycetoma

Ramsay–Hunt syndrome

It is due to reactivation of varicella zoster virus infection of the geniculate ganglion and is characterized by triad of facial palsy with vesicles of the ear canal, tongue and/or hard palate, and earache. Other manifestations include taste loss of the anterior two-thirds of the tongue, and a dry mouth and eyes.[6]

Tabes dorsalis

It is the most common form of neurosyphilis characterized by a triad of symptoms (lightning pains, dysuria, and ataxia) and a triad of signs (Argyll Robertson pupils, areflexia, and loss of proprioceptive sense).[7]

Autoimmune

Atopic triad

The term ‘atopy’ was coined by Perry, as quoted by Coca and Cooke, to describe this triad of atopic eczema, allergic rhinitis, and asthma.[8]

Behçet's syndrome

Behçet's syndrome is a chronic, multisystem disorder characterized by the association of recurrent aphthous stomatitis with recurrent genital ulceration [Figure 3] and eye disease (especially iridocyclitis and retinal vasculitis). Other manifestations include optic atrophy, meningoencephalitis, pustules, erythema nodosum, positive pathergy, proteinuria and haematuria, thrombophlebitis, aneurysms, and arthralgias.[9,10,11]

Figure 3.

(a) Aphthous stomatitis (b) genital ulceration in Behçet's disease

Graves’ disease (Diamond's triad)

Graves’ disease is an autoimmune disorder in which there is a high incidence of antithyroid antibodies leading to hyperthyroidism. Pretibial myxedema (localized edematous and thickened pretibial plaque formation), thyroid acropachy (clubbing of the fingers and toes associated with soft-tissue swelling of hands and feet and with periosteal new bone formation), and exophthalmos are features of Graves’ disease (collectively known as Diamond's triad).[12,13]

Sjögren's syndrome (Mikulicz disease, Sicca syndrome)

Sjögren's syndrome is an autoimmune disorder that affects primarily secretory glands, in particular the lacrimal and salivary glands. The classic triad consists of keratoconjunctivitis sicca, xerostomia, and arthritis. Cutaneous manifestations include xerosis, petechiae, purpura (palpable and non-palpable), urticarial vasculitis, and annular erythema.[14,15]

Graham Little–Piccardi–Lassueur syndrome

It is a variant of lichen planopilaris characterized by the triad of multifocal scalp cicatricial alopecia, non-cicatricial loss of pubic and axillary hairs, and keratotic lichenoid follicular papules.[16,17]

Wegener's granulomatosis

It is classically described as a triad consisting of systemic small vessel vasculitis, necrotizing granulomatous inflammation of both the upper and lower respiratory tracts, and pauci-immune glomerulonephritis.[18]

Hyper-IgE syndrome

It is characterized by classic triad of recurrent cutaneous and sinopulmonary infections, chronic eczematoid dermatitis, and elevated serum IgE (usually in the range: 2,000-40,000 U/l).[19]

Churg–Strauss syndrome

It is characterized by triad of asthma, peripheral blood eosinophilia, and necrotizing granulomatous vasculitis that involves small- to medium-sized vessels.[20]

Still's disease

Systemic-onset juvenile idiopathic arthritis, also known as Still's disease, is characterized by triad of high spiking fevers, arthritis, and an urticarial eruption (transient cutaneous eruptions of erythematous macules and papules).[21]

Metabolic

Pellagra

It represents the classic form of vitamin B3 (niacin) deficiency characterized by classical triad of clinical features: Dermatitis, diarrhea, and dementia. The dermatitis begins as symmetric erythema in sun-exposed areas that later become scarlet or hyperpigmented with desquamation and crusting [Figure 4]. In addition to diarrhea, abdominal pain and achlorhydria may be present. Dementia develops in the setting of prolonged niacin deficiency; patients are depressed, apathetic, irritable, anxious and in severe instances, have frank disorientation.[22,23]

Figure 4.

(a) Erythema in sun-exposed areas (b and c) hyperpigmentation with desquamation in pellagra

HAIR-AN syndrome

It is the triad of hyperandrogenism, insulin resistance, and acanthosis nigricans in women.[24]

Primary systemic amyloidosis

It is a condition characterized by abnormal extracellular deposition of amyloid in tissues associated with plasma cell dyscrasia or multiple myeloma. The diagnosis should always be considered when a patient presents with the triad of carpal tunnel syndrome, macroglossia, and mucocutaneous skin lesions (waxy nodules and plaques, ecchymoses, and pinch purpura) [Figure 5].[25,26]

Figure 5.

(a) Ecchymoses (b) macroglossia in primary systemic amyloidosis

Scleromyxedema

It is a chronic idiopathic disorder characterized by numerous firm waxy papules and areas of induration that are due to microscopic triad of increased dermal mucin, an increase in dermal collagen deposition, and marked fibroblast proliferation.[27,28]

Pancreatic panniculitis (Schmid's triad)

In pancreatic panniculitis, erythematous, edematous subcutaneous nodules develop, most often on the legs but also on the abdomen, chest, arms, and scalp. Its association with polyarthritis and eosinophilia is known as Schmid's triad, and is associated with a poor prognosis.[29,30]

Genodermatoses

Tuberous sclerosis (epiloia)

It is an autosomal dominant disorder of multisystem hamartomatosis characterized by classic triad of seizures (epilepsy), mental retardation (low intelligence), and adenoma sebaceum (angiofibroma). Other cutaneous manifestations include ash leaf macule, shagreen patch, and periungual fibroma Figure 6.[31]

Figure 6.

(a) Ash leaf macule (b) adenoma sebaceum (c) periungual fibroma, and (d) shagreen patch in tuberous sclerosis

Netherton's syndrome

It is a rare autosomal recessive genodermatosis characterized by triad of congenital ichthyosiform erythroderma (later ichthyosis linearis circumflexa may develop), trichorrhexis invaginata (bamboo hair), and atopic diathesis with failure to thrive.[32]

Dyskeratosis congenita (Zinsser–Cole–Engman syndrome)

This is a multisystem ectodermal dysplasia, in which a triad of cutaneous abnormalities are the most consistent and diagnostic feature, comprising reticulate hyperpigmentation of the skin, nail dystrophy (longitudinal ridging, splitting and early pterygium formation), and leukokeratosis of mucous membranes [Figure 7]. Aplastic anemia occurs in 50% of patients. Dental, skeletal, ocular, and gastrointestinal abnormalities; mental retardation, short stature, and premature ageing also occur. Most cases have X-linked recessive inheritance.[33]

Figure 7.

(a and b) Reticulate hyperpigmentation (c) nail dystrophy in dyskeratosis congenita

Wiskott-Aldrich syndrome

It is a X-linked recessive immunodeficiency disorder characterized by the classic triad of atopic-like dermatitis, a bleeding tendency due to microthrombocytopenia, and recurrent sinopulmonary infections.[34]

DiGeorge syndrome

It is classically recognized by the triad of congenital heart defects, immunodeficiency secondary to thymic hypoplasia, and hypocalcaemia secondary to parathyroid gland hypoplasia.[35]

Hermansky–Pudlak syndrome

It is an autosomal recessive disorder of melanosome biogenesis presenting with a triad of oculocutaneous albinism, hemorrhagic diathesis due to the absence of dense bodies in platelets, and deposition of ceroid-like material within lysosomes in affected internal organs, including the lungs and gastrointestinal tract.[36]

Scleroatrophic syndrome of Huriez

This autosomal dominant congenital syndrome comprises a triad of diffuse scleroatrophy of the hands, mild palmoplantar keratoderma, and hypoplastic nail changes such as prominent lunulae, elongated cuticles, longitudinal and transverse ridging, increased longitudinal curvature, and V-shaped notches.[37]

Birt–Hogg–Dubé syndrome

This syndrome is an autosomal dominant genodermatosis characterized by classic triad of multiple trichodiscomas, trichofolliculomas, and acrochordon-like lesions. It is also associated with lung cysts, spontaneous pneumothorax, and renal neoplasms (chromophobe renal carcinoma and oncocytoma).[38,39,40]

Neoplasm

Sézary syndrome

It is defined as the presence of a clinical triad consisting of generalized exfoliative erythroderma, peripheral lymphadenopathy, and atypical mononuclear cells (Sézary cells) comprising 5% or more of peripheral blood lymphocytes on a buffy coat smear, or more than 20% of total lymphocyte count, or a total Sézary count of more than 1000 × 10⁹/L.[41,42]

Hand–Schüller–Christian disease

It is a type of Langerhans cell histiocytosis characterized by triad of diabetes insipidus, bone lesions, and exophthalmos.[43]

Miscellaneous

Follicular occlusion triad

This term was coined by Pillsbury, Shelley, and Kligman in 1956 for the common association of acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp. They proposed that the pathological event unique to each disease was follicular hyperkeratinization.[44,45]

Methotrexate osteopathy

It is a little-recognized complication of long-term low-dose methotrexate treatment. The affected patients present with the triad of severe pain localized to the distal tibia, osteoporosis, and compression fractures of the distal tibia. The condition is readily confused with psoriatic arthropathy and, as the only treatment is said to be withdrawal of methotrexate, it is important that it should be recognized.[46]

Melkersson-Rosenthal syndrome

Lingua plicata (fissured or furrowed tongue), facial paralysis/ptosis, and granulomatous cheilitis define the clinical triad of Melkersson-Rosenthal syndrome. However, granulomatous cheilitis presents as the sole manifestation in approximately one-third to one-half of patients.[47]

Meltzer's triad

The classic presentation of mixed (types II and III) cryoglobulinaemia is characterized by triad of recurrent showers of dependent palpable purpura, asthenia, and arthritis or arthralgia.[48,49]

Yellow nail syndrome

Yellow nail syndrome is the triad of yellow nails, primary lymphedema, and pleural effusion. The characteristics of the nails also include thickening, transverse ridging, diminished growth, increased curvature, and onycholysis. The nail changes are secondary to congenitally hypoplastic lymphatics, leading to slowly progressive and somewhat asymmetric lymphedema, with induration and hyperkeratosis extending to the thighs.[50]

Klippel–Trenaunay syndrome

It consists of triad of capillary malformations (port-wine stain/nevus flammeus), venous malformations (abnormal varicosities, persistent embryonal veins, and sometimes agenesis of deep veins or avalvulosis), with disproportionate limb growth of soft tissue and/or bone [Figure 8].[51,52]

Figure 8.

Disproportionate limb growth with venous malformations in Klippel-Trenaunay syndrome

Adiposis dolorosa (Dercum's disease)

It is characterized by classic triad of painful deposits of adipose tissue occurring over multiple areas of the body, ecchymoses and obesity, appearing usually in post-menopausal women with amenorrhea and neurotic symptoms.[53]

What is new?

An attempt has been made to group the various triads on the basis of their etiologies.