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Part I: Retiform Purpura: A Diagnostic Approach

Corey Georgesen, MD, Lindy P. Fox, MD, Joanna Harp, MD

PII: S0190-9622(19)32672-6
DOI: https://doi.org/10.1016/j.jaad.2019.07.112
Reference: YMJD 13788

To appear in: Journal of the American Academy of Dermatology

Received Date: 9 May 2019

Revised Date: 15 July 2019
Accepted Date: 28 July 2019

Please cite this article as: Georgesen C, Fox LP, Harp J, Part I: Retiform Purpura: A Diagnostic
Approach, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/
j.jaad.2019.07.112.

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Part I: Retiform Purpura: A Diagnostic Approach

Corey Georgesen, MD1; Lindy P. Fox, MD2; Joanna Harp, MD3

1. University of Pittsburgh Medical Center, Dept. of Dermatology

2. University of California, San Francisco, Dept. of Dermatology
3. Weill Cornell Medicine, Dept. of Dermatology

Correspondence:
Corey Georgesen, MD
UPMC Dermatology
9000 Brooktree Rd, Suite 200
Wexford, PA, 15090
Fax: 724-933-1338
corey.georgesen@gmail.com

Word and Figure Count:

Part I: 2,819 words; 12 Figures, 1 Table

All authors have approved the manuscript in its final form, and we have no conflicts of interest
nor financial obligations to disclose.
Retiform purpura is a specific morphology within the spectrum of reticulate eruptions of vascular

origin. This morpology develops when blood vessels serving the skin are compromised resulting

in downstream cutaneous ischemia, purpura, and necrosis. Blood vessel compromise occurs by

one of two mechanisms, 1) vessel wall damage (vasculitis/depositional disease/angioinvasion by

organism) or 2) vessel lumen occlusion (thrombotic or embolic disease). Understanding the

mechanisms that lead to retiform purpura helps inform the differential diagnosis.1-3

Recognition of retiform purpura is paramount, especially in the acute or severely ill patient, as it

may elucidate the underlying diagnosis, provide prognostic information, and suggest a treatment

approach. The differential diagnosis of retiform purpura is vast, reflecting the myriad conditions

that can lead to cutaneous vessel wall damage or lumen occlusion. For example, a patient with

bacterial sepsis may develop direct bacterial angioinvasion, reactive leukocytoclastic vasculitis,

bacterial vaso-occlusive emboli, and/or disseminated intravascular coagulation, all of which can

present with retiform purpura, although each through a distinct mechanism. Herein we describe

an overview of the differential diagnosis of this cutaneous morphology, provide an approach to

workup, and highlight updates in treatment of some of the more common conditions that

manifest as retiform purpura.

2
We suggest the following clinical approach to the patient with retiform purpura:

1) What is the morphology of the lesion?

2) What is the status of the patient?

3) What is the location of the lesion?

4) What is the patient’s past medical and family history?

5) Are there any pertinent positives on review of systems?

6) Are there any additional relevant physical exam findings?

This six-step approach is designed to guide the clinician towards a narrowed differential

diagnosis based on patient history and physical exam. However, it is important to note that most

(if not all) patients with new onset retiform purpura warrant a skin biopsy and laboratory

workup.

Step One. Morphology of the lesion.

• Retiform purpura refers to a distinct clinical morphology.

• The differential diagnosis consists of pathophysiology centered on either the vessel

lumen or the vessel wall.

First, what does retiform purpura mean from a morphologic perspective? These lesions present

with a branching (reticular), non-blanching (purpuric) patch or plaque, which can occur

anywhere on the body or mucous membranes.3 Lesions of retiform purpura are persistent and

often accompanied by frank or impending central necrosis and/or ulceration. This contrasts with

3
other reticulate eruptions of vascular etiology including livedo reticularis and livedo racemosa.

Livedo reticularis4 results from only partial or intermittent reduction of cutaneous blood flow

leading to non-fixed, dusky patches forming complete rings reflecting the underlying cutaneous

vasculature. (Figure 1A) Livedo racemosa, which is representative of a more irregular and

significant reduction of blood flow, presents with broken rings that are persistent but rarely

necrotic or ulcerative.5 (Figure 1B)

Unlike livedo, retiform purpura does not display the net-like pattern of rings, but instead displays

branching at the periphery of a purpuric or necrotic center. Some authors have described it as

“river-like” or “serpentine purpura,” and others note that the lesions may appear as “puzzle

pieces” of livedo fit together.3 Lesions may be exquisitely painful reflecting the complete

obstruction of blood flow to the skin with resultant ischemia and necrosis.2 We have provided

representative lesions of retiform purpura (Figure 1A-D) to display the varied clinical

presentation of these lesions. With experience and pattern recognition, these lesions are often

immediately obvious.

Figures 2 summarizes the differential diagnosis of retiform purpura. When considering this vast

differential, we find that it is helpful to first consider (and then confirm with skin biopsy)

whether the disease pathology is within the vessel wall or the vessel lumen. If the disease

centers on the vessel wall, the differential diagnosis includes depositional diseases (such as

calciphylaxis6), angioinvasive organisms and vasculitides. While palpable purpura is the classic

manifestation of small vessel vasculitis, concomitant retiform purpura indicates that a medium

vessel component is also present. Thus, purely medium vessel vasculitides such as polyarteritis

4
nodosa7, in addition to small and medium mixed vessel vasculitides such as IgA vasculitis8 and

cryoglobulinemia9, can occasionally present with retiform purpura, though this is not the most

common presentation. On the other hand, if cutaneous histology reveals blockage of the vessel

lumen, the differential diagnosis centers upon thromboembolic processes. Occlusion of

cutaneous blood vessels can occur through a wide variety of mechanisms including

hypercoaguable states (antiphospholipid syndrome10, disseminated intravascular coagulation,

genetic disorders), platelet plugging (thrombotic thrombocytopenic purpura (TTP), hemolytic

uremic syndrome (HUS), heparin induced thrombocytopenia (HIT)), elevated or dysfunctional

red and white blood cells (polycythemia vera, sickle cell anemia, intravascular lymphoma),

temperature-related processes (cryoglobulinemia11, cryofibrinogenemia), and finally embolic

processes (septic, cholesterol, marantic). (Figure 23,5,12-14)

In an effort to narrow this wide differential diagnosis, some authors have recommended

categorizing lesions as either “inflammatory” retiform purpura, or “non-inflammatory” retiform

purpura.2-3 “Inflammatory” retiform purpura refers to the clinical presence of erythema around

the lesion (accounting for a minimum of 2/3 of the lesion) with ≤ 1/3 of the lesion accounted for

by central impending necrosis. “Inflammatory” retiform purpura suggests a vasculitic or

infectious process. “Non-inflammatory” retiform purpura2-3 refers to clinical lesions presenting

with 2/3 central frank or impending necrosis and ≤ 1/3 surrounding erythema and suggests an

occlusive process. While this clinical categorization can be helpful in many cases, it is important

to note that significant overlap exists. In addition, a few select diseases, i.e. cryoglobulinema,

sepsis, and levamisole associated retiform purpura, may have both vasculitic and thrombotic

pathophysiologic components. Therefore, while the degree of inflammation may be suggestive, a

5
strategized laboratory and pathologic evaluation (as detailed in subsequent sections of this

manuscript) is necessary in all cases.

A final helpful clue when inspecting the morphology is the perceived acuity of the lesion. In a

patient with multiple lesions of varying stages with atrophie blanche-like scarring of older

lesions, one might surmise that skin lesions are resultant from a chronic, smoldering, intermittent

process such as liveoid vasculopathy18. (Figure 3) In contrast, a patient with new onset of many

lesions, all in a similar stage of development, may suggest a more acute, active process such as

purpura fulminans (Figure 4) or a medication induced processes such as warfarin induced skin

necrosis or hepatin induced thrombocytopenia.2,5,19 (Figure 5)

Step Two. Status of patient.

• Acute retiform purpura in a sick patient should prompt a search for serious and reversible

causes.

• It may be appropriate to send an initial battery of tests while awaiting skin biopsy results.

The next checkpoint is straightforward yet crucial. The clinician should briefly pause to consider

the overall health of the patient. If, for example, the patient is severely ill, the clinician must first

and foremost consider rapidly progressive, potentially fatal, and reversible causes. In many

cases, this will mean proceeding with an initial battery of tests and urgent skin biopsy prior to

moving any further in this diagnostic six-step algorithm.

6
In the emergent setting, when the patient presents with retiform purpura, fever, altered mental

status, organ failure, and/or septic shock, we suggest a workup as outlined in Figure 620-30. Of

course, workup should be discussed and followed with the intensivists, internists, and

appropriate consultants. The dermatologist should pursue an immediate skin biopsy for

hematoxylin and eosin (H&E) and tissue culture and direct immunofluorescence when

appropriate. In the patient with systemic infection, tissue culture from the skin may identify the

offending organism and provide antimicrobial sensitivity data. Broad-spectrum antibacterial and

antifungal coverage should be initiated in septic or immunocompromised patients while awaiting

results. The clinician should review the patient’s labs including platelet count and coagulation

studies to evaluate for evidence of disseminated intravascular coagulation (DIC). Review of

medications should be rapidly undertaken to identify if the patient is on any high-risk

medications (newly started heparin or warfarin or drugs that can cause ANCA+ vasculitis) that

may need to be held or changed while work up is underway.

Step Three. Lesion Location.

• Certain items on the differential diagnosis have characteristic anatomic locations.

• Disseminated retiform purpura can encompass both infectious and non-infectious causes.

7
The anatomic distribution of retiform purpura can guide the clinician. (Figure 7) Some locations

are classic, such as the free cartilage of the ear in levamisole-induced purpura31-32 (Figure 8) and

peri-umbilical “thumbprint” purpura in disseminated strongyloides.33

Acral retiform purpura, especially on distal areas of the fingers and toes, should alert the

clinician toward a possible embolic cause or cold-associated disease. Acral lesions (retiform

purpura or a purpuric digit) accompanied by a recent cardiac procedure and an elevated

eosinophil count suggest cholesterol emboli.34 (Figure 9) Patients with acral lesions and sepsis

should be examined for cutaneous findings of endocarditis, including splinter hemorrhages,

Janeway lesions (nontender, small petechiae on the palms and soles), and Osler nodes (painful

erythematous papules), and an echocardiogram should be considered.35-36 In a patient with a

history of systemic lupus, non-infective (marantic) endocarditis should be ruled out.37

Cryoglobulinemia (type I occlusive disease in the setting of myeloproliferative diseases and

types II and III associated with cutaneous vasculitis) favors acral areas, including the ears and the

nose, where body temperatures are lower.12

In lesions occurring predominantly on the lower extremities, vasculitides may be higher on the

differential (especially if seen in conjunction with palpable purpura). If patients present with

small punched out ulcerations and atrophie blanche (indicating chronicity) on the shins and

dorsal feet, with a background of livedo, consider livedoid vascuopathy. In patients from

Mexico and the Caribbean with lepromatous leprosy, an additional consideration would be the

Lucio phenomenon.38-39

8
Purpuric lesions occurring on fatty areas of the abdomen and thighs might suggest warfarin or

heparin induced skin necrosis. Warfarin induced skin necrosis classically starts within the first

ten days of warfarin initiation (most often on days 3-5), when protein C levels hit nadir, and

often occurs on the abdomen, thighs, buttocks, and breasts.5

Ecthyma gangrenosum40 and meningococcemia5,41 may present with acute disseminated lesions.

In the setting of acute widespread purpura without an infectious source, catastrophic

antiphospholipid syndrome, purpura fulminans, and calciphylaxis42 (uremic or non-uremic)

should be considered.

Step Four. Medical and Family History.

• Next collect relevant medical and family history.

• Use previous clues for guidance.

For all patients with retiform purpura, we suggest thinking through the following set of general

medical and family history questions, which should be specifically tailored to the location and

acuity of the lesions:

1) Does the patient have any relevant personal or family history?

a. End stage renal disease is associated with calciphylaxis.9

b. Connective tissue disease can be associated with antiphospholipid syndrome.

Additionally, small and medium vasculitis can be seen in the setting of Sjogren’s

9
 syndrome and rheumatoid arthritis. Mixed cryoglobulinemia can be seen in the

setting of rheumatoid arthritis and lupus.43

c. Previous history of cerebrovascular accident or spontaneous abortion may be

indicative of the antiphospholipid syndrome.44

d. History of severe asthma or nasal polyposis as can be seen in eosinophilic

granulomatosis with polyangitis.45-46 Ear, nose, and airway manifestations are

also common presenting symptoms in polyangitis with granulomatosis.47

e. Hepatitis is associated with cryoglobulinemia type II and III5,43 and polyarteritis

nodosa5.

f. If history of malignancy, IgA (and/or leukemic vasculitis) should be considered.48-

55

g. History of hereditary hemoglobinopathies such as sickle cell disease, thalassemia,

and spherocytosis must be asked.

h. A family history of myeloproliferative disorders would highlight a tendency

towards a hematologic disease that may present with cryoglobulinemia56.

2) Does the patient have any recent or active infections?

a. Disseminated intravascular coagulation and purpura fulminans can occur in the

setting of various infections, especially encapsulated Gram positive bacteria.2,5,57

b. Ecthyma gangrenosum is associated with Gram negative sepsis.

c. Hemolytic uremic syndrome has been associated with Shiga-toxin producing E.

Coli, pneumococcus, and influenza, among others.58

d. Cold agglutinins are associated with infections, most commonly Mycoplasma

pneumoniae.59

10
 e. Cutaneous polyarteritis nodosa is commonly associated with streptococcal

infection.5,10

f. Streptococcal and upper respiratory viral infections are associated with IgA

vasculitis (Henoch Schonlein purpura).60

g. Angioinvasive fungal infections typically present in severely

immunocompromised patients with signs of infection but who are not responding

to broad antibiotic coverage.

3) Has the patient started any new medications or had exposure to illicit drugs?

a. Warfarin induced necrosis and heparin induced thrombocytopenia most often

occur within the first 3-5 and 7-10 days of initiation, respectively5

b. Certain medications, most commonly tumor necrosis factor (TNF) inhibitors,

propylthiouracil, hydralazine, minocycline, rituximab, and statins, among many

others, have been implicated in drug induced vasculitis.61

c. Levamisole contaminated cocaine is associated with retiform purpura classically

of the ears and acral areas.31-32

4) Has the patient undergone recent instrumentation?

a. Embolization, most notably cholesterol emboli, are commonly associated with

cardiac procedures.34

Step Five. Review of systems.

• Review of systems should be tailored toward the patient.

• Cutaneous vasculitis necessitates a search for systemic involvement.

11
A comprehensive review of systems for the patient presenting with retiform purpura can be

found in Table 12,3,5, 15-17, 19, 43, 62-67. However, it must be emphasized that the review of systems

can (and should) be focused on entities highest on the differential diagnosis. For example, in the

patient with retiform purpura and deep vein thrombosis, be sure to ask about pulmonary

symptoms given concern for pulmonary embolism. In the patient from an endemic area, consider

strongyloides and ask about malaise, fatigue, and pulmonary or gastrointestinal symptoms. In

the patient with streptococcal infection, ask about abdominal pain, joint pain, and change in urine

color.

Finally, whenever vasculitis is suspected, systemic involvement must be ruled out with the

review of systems, in addition to the physical exam and laboratory workup. Systems affected by

the various vasculidites include: neurologic (cerebrovascular accident, mononeuritis multiplex),

ocular, head and neck (epistaxis, sinusitis), pulmonary (hemoptysis or chest pain), cardiac (chest

pain), abdominal (pain, diarrhea, melena), musculoskeletal (arthralgia), and renal (change in

urine color).2,7,17,43,63

Step Six. Associated Physical Exam Findings.

• Thorough physical examination is requisite in patients with retiform purpura.

• Full skin examination is important as obscured areas can have diagnostic clues.

12
As outlined, previous steps in this diagnostic algorithm involve assessing lesion morphology,

degree of inflammation, and location. A full physical examination is also essential to fully

evaluate the patient who presents with retiform purpura. The heart and lung examination as

performed by the intensivist should be reviewed for associated findings (the murmur of bacterial

endocarditis, friction rub of pericarditis, rales of interstitial lung disease, etc.) A musculoskeletal

exam should be performed. Muscles strength should be assessed with an emphasis on the pelvic

and shoulder girdles. Careful palpation for lymphadenopathy should be performed.68-70

The final step in the diagnostic algorithm is a complete and thorough skin examination. A

myriad cutaneous exam findings can give support to the suspected diagnosis.

Going (anatomically) from top to bottom, the physician should start in the scalp, looking for any

sign of scarring alopecia as may be associated with connective tissue disease. The conchal bowls

can be examined for signs of chronic cutaneous lupus. All mucous membranes should be

inspected. Conjunctival hemorrhage can be suggestive of a platelet diathesis or disseminated

intravascular coagulation.71 The nares deserve inspection, as nasal polyps and angioinvasive

fungi (mucormycosis) can be obvious without endoscopy. The oral mucosa should be carefully

examined for signs of ulceration, purpura, or xerostomia. Additionally, the clinician can look for

the strawberry gingivitis of polyangitis with granulomatosis.72-75

The dermatologist should perform a full skin exam of the trunk, extremities, and genitals. The

patient should be repositioned when necessary to observe obscured areas. No area should be

neglected; areas under chest leads, adhesives, and surrounding I.V. sites must be examined, as

13
diagnostic lesions may otherwise remain concealed. (Figure 10) These are also potential sites of

inoculation of invasive fungal organisms in the immunosuppressed hospitalized patient.

Finally, the nails deserve close inspection. Koilonychia, or spoon nails, can be observed in

anemia that is associated with malignancy, autoimmune, or other chronic disease.76 Lindsay’s

nails, or half and half nails, may be associated with chronic renal disease.77 Terry’s nails are

associated with cirrhosis as can be seen in hepatitis C.78 Muehrcke’s nails, which present as

parallel lines of blanchable leukonychia (pathology of the nail bed), are associated with low

protein states such as nephrotic syndrome or liver disease.79 The proximal nailfold should be

inspected for the presence of vascular dropout, meandering and dilated vessels, or frayed cuticles

(Samitz sign80), which can signify the presence of autoimmune connective tissue disease.81-83

Finally, in the immunocompromised patient, nails should be inspected for inflammation and

subungual discoloration, as fusarium and other angioinvasive organisms can disseminate from a

primary cutaneous paronychia or onychomycosis.84-85

Completing the Workup

• Biopsy location should be selected to maximize probability of capturing representative

pathology.

• Laboratory evaluation will vary and is dependent upon previous steps detailed in the

diagnostic algorithm.

14
Now the clinician is prepared to complete the diagnostic workup by performing a biopsy for

H&E (plus tissue culture and/or direct immunofluorescence as deemed appropriate) and

collecting laboratory data.

Biopsy should be collected at the peripheral purpuric rim of the lesion. When hemorrhagic

bullae are present, as is often the case in bacterial and fungal sepsis, fluid can be obtained for

bacterial culture and the blister roof should be scraped for potassium hydroxide examination. In

other cases, biopsy specimens can be smeared on a glass slide for touch preparation, as described

by other authors.86 Finally, in patients with suspected infection, consider obtaining a second

biopsy from the necrotic center for tissue culture.87

The differential diagnosis of retiform purpura informs the laboratory evaluation. The extent and

timing of laboratory work up will vary depending on the acuity of the skin manifestations, the

overall health of the patient, and any relevant history and physical exam findings that may

narrow the differential. If the patient is severely or acutely ill, it may be reasonable to send many

tests immediately to try to narrow the differential while biopsy results are pending. If skin

lesions are more chronic and/or stable, it may be preferable to await biopsy results, confirm if the

pathology is in the vessel wall or lumen, and then work through the evaluation based on a

narrowed differential diagnosis. Retiform purpura laboratory evaluation is detailed in Figure

113,5,15-17, 19,22,27,34,4363-64,88.

Prompt treatment should follow. Part II of this CME will detail these steps in relation to four of

the most common causes of retiform purpura.

15
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Figure Legends.

Figure 1. (a) Livedo reticularis: Note the presence of complete rings. These are transient and

often temperature related. (b) Livedo racemosa: Note the presence of broken, irregular, fixed

rings.

Figure 2. Retiform purpura in a patient with (a) calciphylaxis, (b) septic vasculitis, (c) IgA

vasculitis, and (d) disseminated intravascular coagulation

Figure 3. Differential diagnosis of retiform purpura based on pathophysiology.

Figure 4. Livedoid vasculopathy in a 39-year-old female with anti-phospholipid syndrome.

Figure 5. Pupura fulminans in presenting patients admitted to the intensive care unit.

Figure 6. Heparin induced thrombocytopenia-induced retiform purpura.

Figure 7. Workup for retiform purpura in the acutely ill patient.

Figure 8. Anatomic distribution of common causes of retiform purpura.

Figure 9. Levamisole-induced retiform purpura. (Photograph courtesy of Christine Ahn, MD).

30
Figure 10. Retiform purpura in the setting of cholesterol emboli following cardiac

catheterization.

Figure 11. The “bullseye infarct” purpuric lesions of mucormycosis:

A 6-year old with acute lymphoblastic leukemia presented with retiform purpura (a) next to an

intravenous puncture site that evolved into a non-retiform purpuric plaque.

A 52-year-old with in septic shock presents with a purpuric patch (c-d) under a chest lead. While

not retiform in this photograph, systemic fungal infections can sometimes present with retiform

lesions that quickly evolve into different morphologies.

Figure 12. Retiform purpura laboratory evaluation.

Table 1. Complete retiform purpura review of systems.

31
System Symptom Associations

connective tissue disease, leukemia/lymphoma, chronic infections (hepatitis, malaria, parasitic),

General fatigue endocarditis, anemia (sickle cell, paroxysmal nocturnal hemoglobinuria)
weight changes malignancy, chronic infections
connective tissue disease, leukemia/lymphoma, acute infection (bacterial, fungal), chronic infections
fever (hepatitis, malaria, parasitic), endocarditis, ANCA vasculitis

conjunctival
hemorrhage (red
Ocular eye) hemoglobinopathies, TTP, HUS, DIC, connective tissue disease

vision change vasculitis (ANCA, leukemic, septic, cryoglobulinemia), infection (mucormycosis)

hearing change,
Ear tinnitus vasculitis (ANCA, leukemic, septic, cryoglobulinemia)

Nose epistaxis vasculitis (polyangitis with granulomatosis), thrombocytopenia (TTP, HUS, DIC)
sinusitis eosinophilic granulomatosis with polyangitis

Mouth xerostomia Sjogrens syndrome, connective tissue disease

recurrent ulcers connective tissue disease

connective tissue disease (lupus), infection (meningococcemia, angioinvasive fungi), vasculitis,

Neuro headache cryoglobulinemia

altered mental status infection (sepsis), TTP

numbness, loss of vasculitis (ANCA, polyarteritis nodosa), leprosy, cerebrovascular accident (antiphospholipid
sensation syndrome)
loss of motor vasculitis (ANCA, polyarteritis nodosa), leprosy, cerebrovascular accident (antiphospholipid
function syndrome)
seizure connective tissue disease (lupus)
Respiratory chest pain connective tissue disease (pleuritis), hypercoagulative state (embolus)
connective tissue disease (pulmonary hypertension, interstitial lung disease), hypercoagulative state
shortness of breath (embolus), infection (endocarditis, pneumonia)
hemoptysis infection (pneumonia), vasculitis (granulomatosis with polyangitis)

Cardiovascular chest pain connective tissue disease (carditis), cardiomyopathy (eosinophilic granulomatosis with polyangitis)
renal disease (calciphylaxis), liver disease (cryoglobulinemia, IgA vasculitis),deep venous thrombosis
edema (hypercoagulative state, antiphospholipid syndrome)
calf pain deep venous thrombosis (hypercoagulative state, antiphospholipid syndrome)

vasculitis (IgA, cryoglobulinemia, leukemic), bowel infarcation (hypercoagulable state, embolus, DIC),
Gastrointestinal pain malignant atrophic papulosis
melena vasculitis (IgA, cryoglobulinemia, leukemic)
lymphoma (leukemic vasculitis, cryoglobulinemia, intravascular lymphoma), malignancy (IgA
appetite change vasculitis), parasite (strongyloides)

jaundice/kernicterus liver disease (cryoglobulinemia, IgA vasculitis)

vasculitis (IgA, ANCA, cryoglobulinemia), connective tissue disease (lupus, systemic sclerosis),
Genitourinary change in color paroxysmal nocturnal hemoglobinuria
dysuria infection (urosepsis)

Musculoskeletal proximal weakness connective tissue disease (dermatomyositis)

arthralgia connective tissue disease (lupus, mixed connective tissue disease), cryoglobulinemia

lymphoma (leukemic vasculitis, cryoglobulinemia, intravascular lymphoma), liver disease

Hematologic ease of bruising (cryoglobulinemia, IgA vasculitis), thrombocytopenia (TTP, HUS, DIC, HIT)

ease of bleeding thrombocytopenia (TTP, HUS, DIC, HIT)