Dermal Diseases




(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA

 



6.1 Inflammatory

6.1.1 Lymphocytic

6.1.2 Granulomatous/Histiocytic

6.1.3 Neutrophilic

6.1.4 Eosinophilic

6.1.5 Mastocytic

6.1.6 Plasmacytic

6.1.7 Mixed Cell Infiltrate

6.2 Neoplastic (See Chap. )

6.3 Depositional

6.3.1 Amyloid

6.3.2 Calcium

6.3.3 Urate

6.3.4 Mucin

6.3.5 Lipid

6.3.6 Pigment Deposition

6.3.7 Hyaline-Like Material Deposition

6.3.8 Implantable Depositions

6.3.9 Porphyrias

6.3.10 Storage Disorders

6.4 Subcutaneous/Panniculitis

6.4.1 Mostly Septal Panniculitis

6.4.2 Mostly Lobular Panniculitis

6.4.3 Other


Abstract

Dermal diseases are centered in the dermis, whether the condition is related to inflammation, neoplasia, deposition, or other processes. When epidermal change is noted, it is not a dominant feature. Given that the depth tends to obscure specific features, the various dermal processes often cannot be differentiated on clinical grounds without a biopsy.


Keywords
Dermal inflammatory diseasesDepositionalPanniculitis



6.1 Inflammatory


Dermal inflammatory diseases are best categorized by their predominant cell type. Clinically, these infiltrative processes display morphologic clues that distinguish them. For instance, it may be possible to confidently diagnose a dermal granulomatous eruption, but it may be difficult to distinguish granuloma annulare from cutaneous sarcoidosis without a biopsy. When examining dermal inflammatory eruptions, use all historical and physical diagnostic clues before asking yourself: what cell line might this represent?


6.1.1 Lymphocytic






  • Mnemonic: dermal lymphocytic processes can be remembered as the “Ls”: Lupus, Leukemia/Lymphoma, polymorphous Light eruption, benign Lymphocytic infiltrate, pseudoLymphoma, Lyme, Lues (syphilis)


  • Lymphocytic dermatoses tend to be erythematous dermal plaques


(a)

Lupus



  • See also Connective Tissue Diseases: Lupus

 

(b)

Leukemia/lymphoma



  • See also Neoplastic: Lymphomas

 

(c)

Polymorphous light eruption (PMLE)



  • Papules/plaques > vesicles > EM-like (each patient only has one morphology) within hours of sun exposure (UVA or UVB), lasts a few days


  • Ddx LE (but no positive serology), EPP (but not painful), EM (but no interface), solar urticaria (but not ephemeral)


  • Path: papillary dermal pallor, superficial and deep perivascular lymphocytes


  • One form = “juvenile spring eruption” – Usually most severe in spring or early summer


  • A delayed-type hypersensitivity to unclear antigen


  • ANA, Ro, La positive in 10–40 % (Ro correlates best of all Ab with photosensitivity)


I.

Hydroa vacciniforme



  • Rare, childhood onset, sunlight-provoked disorder


  • Intermittent, scarring


  • May be a scarring form of PMLE

 

II.

Actinic prurigo



  • May be a variant of PMLE, but distinct


  • Most commonly seen in Native Americans; also cheilitis, conjunctivitis

 

III.

Acne aestivalis (Mallorca acne)



  • Monomophous eruption of red papules on the face from UVA light, no comedones


  • Path with neutrophilic follicular destruction rather than lymphocytes of typical PMLE

 

 

(d)

Benign lymphocytic infiltrate of Jessner’s



  • On head, neck, upper back; papules/plaques, often annular with no secondary changes


  • Overlaps tumid lupus


  • Sometimes grouped with pseudolymphomas

 

(e)

Pseudolymphoma (lymphocytoma cutis, benign cutaneous lymphoid hyperplasia)



  • Benign mimicker clinically/histologically of lymphoma


  • Idiopathic, caused by drugs, insect bites, infections (Lyme)


  • Includes lymphomatoid drug eruption, lymphomatoid contact dermatitis, arthropod-induced pseudolymphoma, actinic reticuloid, lymphocytoma cutis, acral pseudolymphomatous angiokeratoma of children (APACHE), Kikuchi syndrome (flu-like illness with polymorphous eruption, LAD, from a virus?)


  • Path: follows normal anatomical structures, mixed cell types, polyclonal (unlike lymphoma → no regard for anatomy, often destroys structures; monotypic, often atypical morphology, monoclonal); is “top heavy” rather than more monomorphic, “bottom heavy” infiltrate of lymphoma

 

(f)

Other superficial and deep perivascular lymphocytic

I.

Figurate/gyrate erythemas (including Lyme, another L)

 

II.

Syphilis (aka Lues, another L)

 

 


6.1.2 Granulomatous/Histiocytic






  • Granulomatous dermatoses tend to be red-brown/orange dermal plaques, even “apple jelly”-colored, which may be appreciated on diascopy.


(a)

Sarcoidosis



  • Most common in lungs; 1/3 have skin findings


  • Most frequently in African-Americans, highest incidence in Sweden


  • Can involve any organ system, especially pulmonary, skin, ocular, renal, cardiac


  • Consider CXR/PFTs, eye exam, CBC, CMP, U/A, cardiac evaluation (in 20 %, may cause complete heart block); note, ACE level not diagnostic


  • Path: non-caseating “naked” granulomas


  • Kveim test = skin test for sarcoid (not used anymore)


I.

Macular/papular type

 

II.

Subcutaneous nodular sarcoidosis (Darier-Roussy type)

 

III.

Löfgren’s syndrome



  • Triad: hilar LAD, erythema nodosum, arthritis; also uveitis, fever


  • Mnemonic to distinguish Löfgren from Loffler = Grrr…sarcoid… Löfgrrrrren’s


  • Note: Loffler syndrome = respiratory illness associated with eosinophilia, Ascaris and Strongyloides

 

IV.

Lupus pernio



  • Affects coldest areas (nose, ears, cheeks)


  • Associated with chronic sarcoid of the lungs (~75 %) and upper respiratory tract, cystic lesions on distal phalanges


  • May be recalcitrant to treatment

 

V.

Heerfordt’s syndrome (uveoparotid fever)



  • Parotid gland involvement, uveitis, fever, cranial nerve palsies (usually the facial nerve)

 

VI.

Mikulicz syndrome



  • Bilateral enlargement of lacrimal, parotid, sublingual and submandibular glands (sarcoidosis is thought to be one cause, though Mikulicz now being lumped into IgG4- related disease as a larger category)

 

VII.

Angiolupoid sarcoid



  • Can resemble rosacea

 

VIII.

Infiltration of scars, tattoos

 

IX.

Other



  • Annular, hypopigmented, ulcerative, erythrodermic, ichthyosiform (classically on shins), alopecia, morpheaform, mucosal

 

 

(b)

Granuloma annulare (GA)



  • 2/3 of patients under age 30, most on hands/feet/legs


  • Path: palisading granuloma around mucin/degenerated collagen


I.

Localized GA



  • May include interstitial GA subtype, which on path shows less clearly formed granulomas (interstitial)

 

II.

Disseminated/Generalized GA



  • Associated with hyperlipidemia, diabetes (controversial)

 

III.

Interstitial GA

 

IV.

Subcutaneous GA

 

V.

Perforating GA

 

VI.

Arcuate dermal erythema/Patch GA

 

VII.

Annular elastolytic giant cell granuloma (actinic granuloma/GA)



  • There is controversy whether this is a form of GA


  • Path: granuloma without collagen alteration or mucin

 

 

(c)

Interstitial granulomatous inflammation



  • Distinguishing these three entities may be difficult as clinical and pathologic presentations have considerable overlap.


I.

Interstitial granulomatous dermatitis (IGD)



  • May be drug-induced, e.g. from ACE inhibitors, calcium channel blockers, other


  • May be associated with connective tissue disease (RA, SLE, others)


  • Typically occurs after many years on a drug, and may take months-years after drug cessation before resolution (making establishment of a drug association often difficult)


  • Path: interstitial infiltrate of histiocytes, perhaps with eosinophils or interface


  • See also Vascular: Toxic Erythema: Drug Eruptions

 

II.

Interstitial granuloma annulare



  • Path: may show interstitial infiltrate of histiocytes with some mucin, with or without degenerated collagen

 

III.

Palisated neutrophlic and granulomatous dermatitis (PNGD)



  • Path: neutrophilic infiltrate, abnormal collagen, granulomas, and leukocytoclastic debris


  • Seen in context of connective tissue disease (usually SLE or RA)

 

 

(d)

Necrobiosis lipoidica



  • Aka necrobiosis lipoidica diabeticorum (NLD)


  • Most common on shins; violaceous to red-brown atrophic, yellow-brown centered plaques with telangiectasias, may ulcerate


  • Path: “layer cake” of horizontal palisading granulomas around degenerated collagen, “square biopsy”


  • Seen in 0.3 % of all diabetics


  • ~60 % patients diabetic, ~15 % hyperglycemic at presentation

 

(e)

Leprosy (Hansen’s disease)

I.

Lepromatous



  • Low cell-mediated immunity, many symmetric lesions, late nerve damage, Th2 predominant response

 

II.

Borderline (BL, BB, BT)

 

III.

Tuberculoid



  • High cell-mediated immunity, few lesions <5, anesthetic lesions, Th1 predominant response


  • See also Infectious Diseases: Mycobacterial: Typical Mycobacterial

 

 

(f)

Tuberculosis

Types of cutaneous TB:

I.

Exogeneous source

1.

Primary inoculation

 

2.

Tuberculosis verrucosa cutis

 

3.

Tuberculosis cutis orificialis (orificial TB)

 

 

II.

Direct extension

1.

Scrofuloderma

 

 

III.

Hematogenous source

1.

Lupus vulgaris



  • Primarily from hematogenous spread > lymphatic, other

 

2.

Miliary tuberculosis

 

 

IV.

Tuberculid eruptions (reactive)

1.

Papulonecrotic tuberculid

 

2.

Lichen scrofulosorum

 

3.

Erythema induratum



  • See also Infectious Diseases: Mycobacterial: Typical Mycobacterial

 

 

 

(g)

Xanthomas



  • Xanthomas develop from deposition of lipid; this is seen histologically as lipid-laden macrophages (foam cells) in the dermis


  • See also Dermal: Depositional: Lipid

 

(h)

Other granulomatous

I.

Granulomatous rosacea



  • See also Acneiform Diseases: Rosacea

 

II.

Lupus miliaris disseminatus faciei



  • See also Acneiform Diseases: Rosacea

 

III.

Rheumatoid nodule



  • Path: palisading granuloma around fibrin


  • See also Connective Tissue Diseases

 

IV.

Foreign body granuloma



  • From ruptured cyst (#1), suture, silicon, silica, tattoo


  • Polarize to see birefringent material; note that presence of polarized material does not exclude sarcoidosis

 

V.

Infectious granuloma (suppurative)



  • Includes deep fungal, leishmaniasis

 

VI.

Cheilitis granulomatosis (Melkersson-Rosenthal syndrome)



  • Triad of: fissured tongue/scrotal tongue, lip swelling (lower > upper), Bell’s palsy


  • Path: non-caseating granulomas


  • Note: cheilitis glandularis is a lower labial salivary gland hyperplasia (increased risk of SCC)

 

VII.

Cutaneous Crohn’s disease/metastatic Crohn’s disease



  • Clinical: erythematous plaques, often on genitals/buttock (labial/scrotal edema/erythema the classic presentation in kids, could mimic child abuse)


  • May see “knife-cut” ulcers

 

VIII.

Blau syndrome



  • Rare autosomal dominant inherited disease with granulomatous arthritis, uveitis; may mimic sarcoidosis and granuloma annulare

 

 

(i)

Histiocytoses



  • Note: Histiocytoses are diseases caused by infiltration of histiocytes. They appear more inflammatory than neoplastic (no evidence of clonality), but can be very infiltrative and life-threatening


  • Note: there are indeterminate forms of histiocytosis with mixed immunohistochemistry between LCH and non-LCH


I.

Langerhans cell histiocytoses (LCH)

Note: spectrum from HPD to EG to HSCD to LSD



  • Eponyms still used, but focality/system designation may be more precise


  • Aka Histiocytosis X


  • Rash can appear in the skin as hemorrhagic seborrheic dermatitis or like multiple JXGs


  • Path: proliferation of histiocytes in papillary dermis, identified by kidney bean (reniform) shaped nuclei, Birbeck granules (tennis rackets) on electron microscopy


  • Immunohistochemistry = S100(+) (sensitive, non- specific), CD1a(+), langerin(+) (CD207),


  • Langerin = transmembrane protein needed to form Birbeck granules; receptor-mediated endocytosis


  • Malignancies: increased incidence of ALL and retinoblastoma


1.

Hashimoto-Pritzker disease (limited to skin)



  • Aka congenital self-healing reticulohistiocytosis


  • Can relapse, so monitor long-term

 

2.

Eosinophilic granuloma (unifocal)



  • Expanding proliferation on bone, skin, lungs, or stomach


  • Age 7–12 years

 

3.

Hand-Schüller-Christian disease (multifocal, unisystem)



  • Classic triad of exophthalmos, diabetes insipidus (DI), and osteolytic bone lesions (most common at mastoid)


  • DI from infiltration of posterior pituitary by LCH cells


  • Mnemonic: “Popeye the pisser with a hole in his head”


  • Age 2–6 years

 

4.

Letterer-Siwe disease (“See wee”) (multifocal, multisystem)



  • LAD, hepatosplenomegaly, seborrheic dermatitis- like eruption


  • Age < 2 years

 

 

II.

Non-Langerhans cell histiocytoses (NLCH)



  • Macrophage disorders


  • No Birbeck granules on EM (ddx LCH)


  • Immunohistochemistry: typically see HAM56(+), CD68(+) [a macrophage marker], factor13a(+), CD1a (−), usually S100(−) (exception = Rosai-Dorfman)


1.

NLCH, cutaneous self-healing

(a)

Juvenile xanthogranuloma (JXG)



  • Most common histocytosis


  • Usually on head/neck > extremities


  • Associated with NF-1 and JMML (juvenile myelomonocytic leukemia)


  • Path: Touton giant cells (not specific) → may not be in early JXG


  • When multiple, need eye exam to r/o hyphema, glaucoma (can cause blindness) – only 0.5 %, but 40 % of those had multiple JXGs


  • Internal: most common eye > lung

 

(b)

Benign cephalic histiocytosis



  • Brown papules on face, age 1–3, self-limited

 

 

2.

NLCH, cutaneous persistent/progressive

(a)

Papular xanthoma

 

 

3.

NLCH, systemic

(a)

Multicentric reticulohistiocytosis (MRH)



  • Periungual “coral bead” papules/nodules, arthritis mutilans (can be like RA), malignancy association (in 28 %, bronchial, breast, stomach and cervical carcinomas)


  • Path: large histiocytes with “ground glass” or “dusty rose” cytoplasm


  • Immunohistochemistry: CD68(+), S-100(−), CD1a (−)

 

(b)

Xanthoma disseminatum



  • Normolipemic


  • Eruption of hundreds of xanthomas over the body


  • Can develop diabetes insipidus

 

(c)

Rosai-Dorfman disease (sinus histiocytosis with massive LAD)



  • Massive painless cervical LAD; usually benign, resolves spontaneously


  • Path: emperiopolesis: histiocytes with engulfed lymphocytes; also S100 (+), CD1a (−)

 

(d)

Necrobiotic xanthogranuloma (NXG)



  • Ddx: xanthelasma, amyloidosis


  • Usually periorbital, yellow papules/plaques


  • Associated with paraproteinemia (>80 % of cases, most often IgG with κ light chains), multiple myeloma in a minority


  • Path: degenerated collagen surrounded by giant cells (could look like NLD, but not palisaded histiocytes), cholesterol clefts in collagen


  • May be similar to plane xanthoma (which has a stronger association with multiple myeloma)


  • See also Neoplastic: Skin diseases associated with monoclonal gammopathy

 

(e)

Erdheim-Chester disease



  • Rare systemic infiltrative disease of histocytes with significant morbidity/mortality


  • Rarely may have xanthoma or xanthelasma-like skin lesions

 

 

 

 


6.1.3 Neutrophilic






  • Neutrophilic dermatoses tend to be erythematous/edematous/pseudovesicular dermal plaques and ulcers, may demonstrate pathergy


(a)

Sweet’s syndrome – acute febrile neutrophilic dermatosis



  • Favors head/neck/upper extremities


  • Edematous/erythematous papules/plaques that may appear as vesicles/bullae, “juicy,” but are firm (pseudovesiculation)


  • Major criteria:

    1.

    Abrupt onset of cutaneous lesions

     

    2.

    Path consistent with Sweet’s

     




  • Minor criteria:

    1.

    Associated with infection/malignancy

     

    2.

    Fever/constitutional symptoms

     

    3.

    Leukocytosis

     

    4.

    Responsive to prednisone

     




  • Path: diffuse neutrophilic dermal infiltrate, papillary dermal pallor, can have LCV


  • Most associated with malignancies (AML), IBD


  • Can be caused all-trans-retinoic acid or G-CSF or GM-CSF, but drugs only represent <5 % of cases


  • Other associations include post-Strep, minocycline, Bactrim, furosemide


  • Can have pathergy


  • Variant: neutrophilic dermatosis of the dorsal hands

 

(b)

Erythema elevatum diutinum



  • Note: diutinum is pronounced [Die Oo Tin Um]


  • Violaceous, red-brown, or yellowish papules/plaques/nodules on extensor elbows, hands, and knees


  • Can be associated with Strep, HIV, IgA monoclonal gammopathy, many diseases


  • Path: neutrophilic with eosinophils, onion-skin fibrosis, acral skin, ddx granuloma faciale, may have LCV

 

(c)

Pyoderma gangrenosum



  • Classic clinical presentation = non-healing ulcer with gun-metal grey to violaceous undermined, rolled border; may heal with characteristic cribiform pattern


  • Types: ulcerative (most common), bullous (2nd most common), pustular, superficial granulomatous/vegetative


  • Triad of common associations: (1) IBD, (2) Connective Tissue Disease (mostly RA), and (3) Hematologic malignancy


  • Ulcerative often associated with disease in majority (IBD, RA, monoclonal gammopathy, malignancy – usually hematologic)


  • Pustular often in active IBD, bullous in myelodysplastic disease, vegetative does not have strong associations


  • Can have pathergy


  • May present parastomal in IBD patients s/p ileostomy


  • Can be associated with IgA monoclonal gammopathy


I.

Pyostomatitis vegetans



  • May be PG variant orally in UC > Crohn’s


  • “Snail-track” ulcers in mouth

 

II.

PAPA syndrome



  • Sterile pyogenic arthritis, pyoderma gangrenosum, and acne


  • See also Acneiform Diseases

 

III.

PAPASH syndrome



  • Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa


  • See also Acneiform Diseases

 

 

(d)

Behçet syndrome



  • Major criteria: recurrent aphthous ulcers


  • Minor criteria: recurrent genital aphthous ulcers, eye lesions (classically posterior uveitis, also hypopyon), skin lesions (erythema nodosum-like or follicular), pathergy


  • Associated with HLA-B51


I.

Aphthous ulcers



  • Aka aphthous stomatitis/recurrent aphthous ulcers (“canker sores”)


  • Associated with Behçet’s disease, inflammatory bowel disease, cyclic neutropenia, B12 deficiency, HIV


  • May be trauma-induced


  • Ddx herpes

 

II.

Lipshütz ulcers



  • Ddx aphthous ulcers, pathologically similar


  • Large vaginal/labial ulcers associated with viral infection (e.g. EBV)


  • See also Infectious Disease: Viral

 

 

(e)

Bowel-bypass syndrome



  • Aka BADAS = bowel-associated dermatitis-arthritis syndrome


  • Seems to be caused by bacterial overgrowth and immune response; responds to antibiotics or surgery

 

(f)

Granuloma faciale (more mixed infiltrate)

Tags:
May 14, 2016 | Posted by in Dermatology | Comments Off on Dermal Diseases

Full access? Get Clinical Tree
Get Clinical Tree app for offline access