**Progressive Vaccinia Case Scenario**

43yo Male nurse presents for take check on day 7 following smallpox
vaccination. He appears well and his only complaint on ROS is a mild
headache and fatigue. Removal of his vaccination site bandage reveals an
ulcerative lesion measuring approximately 2.5 cm on a non-erythematous
base with scant non-bloody discharge. Due to your concern regarding the
ulcerative presentation and size of the central vaccination lesion, you
arrange for a site re-check in 2-3 days.

The patient fails to keep his scheduled follow-up appointment because he
was not concerned and was feeling well. Instead, he left town to visit
friends. Feeling guilty about missing his appointment, he presents to
the clinic on day 14 following smallpox vaccination. His ROS is
unremarkable and he appears well.

On examination, the central ulcerative lesion now measures 5 cm. The
edge of the lesion has necrotic changes, while the uninvolved skin shows
no signs of inflammation. There are no exudates present. There is no
evidence of maceration and the patient admits that he has not been
covering the lesion because he ran out of bandaging supplies while on
vacation

> **Vax Hx:** Flu '01, Td '93, routine childhood immunizations including
> smallpox vaccine but no scar is detected.
>
> **PMHx:** Cellulitis following needle stick in 1998 which required
> hospitalization for IV antibiotics, PPD 0x0mm '02
>
> **Meds:** Herbals, occasional aspirin
>
> **SH:** Single, surgical nurse supervisor, heavy smoker

1.  **How do you chart his "take"?**

-   *Major reaction*

2.  **Is this an adverse reaction?**

-   yes

3.  **If so; what is your vaccinial AE differential diagnosis?**

-   *Severe take*

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-   *Early progressive vaccinia (suspect underlying immunocompromised
    condition)*

4.  **What is your level of concern for vaccinial adverse reaction on
    Day 7 and Day 14 post-vaccination?**

-   *Day 7 -- moderate concern (severe take vs. PV)*

-   *Day 14 -- significant concern for PV given continue extension, lack
    of pain and inflammation.*

5.  **What in features of the history or exam help you draw this
    conclusion?**

-   *Absence of erythema and other inflammatory changes*

-   *Painless presentation*

-   *Ulcerative changes*

-   *Initial size and continued progression*

-   *Lack of systemic symptoms*

-   *See Clinical Evaluation Tools' (CET) description of PV  Rapid,
    progressive and painless extension of central vaccination lesion OR
    progression without apparent healing after 15 days. Although this
    patient was evaluated on day 14 post-vaccination, he meets the CET
    criteria for "suspected PV" due to the rapid, progressive and
    painless extension of the central lesion.*

-   *Index of suspicion for immunocompromised or immunodeficient
    conditions. Probe for history for risk factors or symptoms to help
    make a clinical diagnosis:*

    a.  *HIV - needle stick, sexual history, IV drug use, transfusions*

    b.  *Cancer -- recurrent infections, constitutional symptoms, easy
        bruising, headache, nonspecific cough.*

6.  **How likely do you think that non-vaccinial etiologies might be
    contributing to the presenting symptoms?**

-   *Unlikely -- why?*

7.  **If this patient did not give a history of smallpox vaccination,
    what would be your non-vaccinial differential diagnosis?**

-   Bacterial superinfection (e.g., ecthyma)

-   Anthrax

-   Arthropod bite with necrosis

8.  **What are your next steps for clinical evaluation?**

-   Repeat history

-   Complete physical exam

-   Basic labs -- (CBC/diff)

-   Immunological work-up (CD4 count, quantitative immunoglobulins,
    other?)

-   Special labs (HIV w/consent)

-   Site culture.

-   Biopsy for bacterial, fungal and viral culture. EM to rule out
    presence of Orthopoxviruses. Evaluation for malignant changes.
    Special studies as indicated.

9.  **Is this a case that you would like to have further consultation?**

-   Yes

10. **Should a VAERS form be completed? If so, who should fill it out?**

-   A VAERS form should be completed but should NOT delay reporting to
    the appropriate Local/State Health Department officials or CDC.

-   CDC will assist in completing the VAERS form for this case.

-   Reporting criteria: all clinically significant adverse reactions
    following smallpox vaccination.

    a.  Serious or unexpected adverse events which require consultation
        or consideration of VIG/cidofovir administration contact
        local/state Health Department officials AND CDC immediately.

    b.  Serious or unexpected and does NOT require consultation or use
        of VIG/cidofovir.  Report within 48 hours to VAERS.

    c.  All other adverse events within one week.

11. **If so, who do you call? And what is your request?**

-   Locally assigned hospital clinician, with referral to infectious
    disease or dermatologist specialist.

-   Local / State Health Department official

-   CDC's Clinician Information Line to request consultation and VIG
    release (Cidofovir is second-line IND therapeutic).

12. **What is the prognosis for this condition?**

> *High mortality rate (\~100%) prior to the introduction of VIG.
> Mortality was significantly reduced following the introduction of VIG
> and older antivirals (\~20*%).

13. **What are the considerations for infection control measures? Should
    this patient continue in his clinical duties?**

-   Group discussion

**QUESTIONS FOR BREAKOUT:**

1.  **The patient is found to be HIV+, what is your prognosis? Would
    your prognosis be different if the patient was newly diagnosed with
    chronic myeloid leukemia (CML)?**

> It appears that the type of immunodeficiency correlates with the
> prognosis for of PV. Anecdotal experience suggests that despite
> treatment with VIG, persons with cell-mediated immune deficits have a
> poorer prognosis than those with humoral deficits (Fenner). It is
> likely that the degree and type of immunocompromised correlates with
> the risk of rogressive vaccinia, although the protective level of
> T-cell count or humoral immunity is unknown.

2.  **Consider a patient who discloses HIV status AFTER vaccination but
    does NOT have an adverse reaction. What would you do?**

> Presently there is no indication for prophylactic use of VIG/Cidofovir
> under IND in an individual with contraindication to vaccination (e.g.,
> pregnancy, eczema/atopic dermatitis or other immunocompromised
> condition) that is inadvertently exposed to vaccinia (either through
> vaccination or close contact. You should report these cases to your
> local/state health department official and the CDC for inclusion in
> the CDC Inadvertent Exposure Registry (call 1-877-554-4625). If an
> adverse reaction develops in these cases, the CDC is available for
> consultation and to facilitate expedited release of VIG/cidofovir as
> clinically indicated.

**DISCUSSION POINTS**

-   Despite screening tools, there will most likely be inadvertent
    vaccination of individuals with contraindications. Therefore, for
    each case that present with adverse reactions and probe for a
    history of risk factors (see *top yellow* box on Clinical Evaluation
    Tools)

-   Adverse Reactions following smallpox vaccination are a CLINICAL
    diagnosis. Use of VIG should NOT be delayed in a patient with severe
    adverse reactions such as PV, EV (with extensive lesions or with
    systemic illness) or GV (severe form). Do not delay administering
    VIG while awaiting confirmation of the suspected underlying
    immunocompromising condition(s) (e.g., HIV, Cancer or other
    immunodeficiencies)

-   Consider avoidance of ASA in viral infections due to theoretical
    risk of Reye's syndrome.

**GOALS:**

1.  Clinical picture of PV spectrum with compare and contrast to a
    "severe ulcerative take".

2.  Therapeutic modalities available and appropriate indications.

3.  Understand the historical experience with PV prognosis in patients
    with immunodeficiencies (e.g., humoral versus cell-mediated
    immunity)

4.  Reporting criteria and timeline.